Oncology
What is UCAN?
Management of Primary Lung Cancer
The Current Treatment of GIST With Reference to Laparoscopic Rese...
Varian Medical Systems International AG, Zug, Switzerland
Phone +41 - 41 - 749 88 44
www.varian.com/aria info.europe@varia...
Volume 3 Issue 2 • August/September 2008 3
Professor Denys Wheatley is Editor of Oncology News, and is Director of BioMedE...
4 Volume 3 Issue 2 • August/September 2008
T
here is little doubt that some of the
most serious cases of cancer are those
...
Cytosafe®
Tough, polypropylene vial developed to reduce the risk
of breakage and leakage
New 300mg vial
Designed with the ...
6 Volume 3 Issue 2 • August/September 2008
Contents
Volume 3 Number 2 August/September 2008
Copyright: All rights reserved...
Date of Preparation: December 2007 1030/10216
Prescribing Information for Innohep®
20,000 IU/ml and Innohep®
Syringe 20,00...
8 Volume 3 Issue 2 • August/September 2008
U
CAN is a charitable company set up to
improve the quality of life for people
...
Volume 3 Issue 2 • August/September 2008 9
• The development of a comprehensive peer support
framework is novel. It entail...
10 Volume 3 Issue 2 • August/September 2008
L
ung cancer is one of the most common
cancers in the Western world, with
arou...
Volume 3 Issue 2 • August/September 2008 11
Treatment strategies
Management of patients with NSCLC can be considered as
ei...
12 Volume 3 Issue 2 • August/September 2008
(Continuous Hyperfractionated Accelerated Radiotherapy) is
a 3-times daily tre...
A lifeline in relapsed NSCLC
Adverse events should be reported. Reporting
forms and information can be found at
www.yellow...
14 Volume 3 Issue 2 • August/September 2008
The Current Treatment of GIST With
Reference to Laparoscopic Resection and
Neo...
Volume 3 Issue 2 • August/September 2008 15
tumour cells. Evidence has shown that survival is dependant
on tumour size (<5...
16 Volume 3 Issue 2 • August/September 2008
of these agents as neoadjuvant treatments in advanced GISTs
is needed to estab...
Uftoral Prescribing Information (UK)
Presentation: Capsules containing 100 mg tegafur and 224 mg uracil.
Therapeutic Indic...
18 Volume 3 Issue 2 • August/September 2008
F
ollowing estimation of pathological
staging using the criteria outlined in p...
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
Volume 3 Issue 2 :August/September 2008
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Volume 3 Issue 2 :August/September 2008

  1. 1. Oncology What is UCAN? Management of Primary Lung Cancer The Current Treatment of GIST With Reference to Laparoscopic Resection and Neoadjuvant Treatment Prostate Cancer reviewed: Part 2 - Treatment Options News Volume 3 Issue 2 :August/September 2008 www.oncologynews.biz In this issue ISSN 1751-4975 Subscribe FREEwww.oncologynews.biz
  2. 2. Varian Medical Systems International AG, Zug, Switzerland Phone +41 - 41 - 749 88 44 www.varian.com/aria info.europe@varian.com ARIA™. The complete Oncology Information System. Providing quality cancer care to patients requires a team effort by all staff in the cancer center. The ARIA Oncology Information System supports oncology practitioners with the tools needed to effectively manage clinical, financial and administrative data in their departments, eliminating the need for films and paper charts. ARIA streamlines the workflow of advanced techniques such as RapidArc™,IMRT, IGRT, adaptive and concomitant therapies. It features a complete chemotherapy manage- ment system with the most sophisticated clinical trials administration and outcomes assessment tools that help to increase efficiency and reduce clinical risk. ARIA offers powerful and flexible communication tools based on DICOM and HL7, which pass treatment strategy relevant information to the right place in ARIA and connected partner systems. ARIA provides Record & Verify functionality for all Linac brands. Comprehensive workflow and information management. Radiation Oncology SurgicalOncology Medical On cology ARIA_210x297_Zug_ESMO_ESTRO_e:Layout 1 10.07.2008 12:46 Seite 1
  3. 3. Volume 3 Issue 2 • August/September 2008 3 Professor Denys Wheatley is Editor of Oncology News, and is Director of BioMedES. He has strong research ties in Albany, Davis, Auckland, Valencia, Detroit, Budapest, St Petersburg, Heidelberg, Zürich and Hong Kong. He is eager to establish strong interaction with cancer and cell biology teams worldwide, and initiate programmes in the areas in which his expertise lies. His work in cancer research, other scientific fields, with IFCB, and in publishing and scientific communication has led to his receiving awards in recent years. Professor Patrick J Bradley is Associate Editor of Oncology News, and, a Head and Neck Oncologic Surgeon at the University Hospital, Nottingham. He is a member of numerous journals’ UK Editorial Boards; Journal of Laryngology and Otology, Oral Oncology, and International Journals: Laryngoscope, Head and Neck, Acta Otolaryngologica Scandinavia, as well as Section Editor of Head and Neck Oncology, and Current Opinions ORL-HNS. Dr Tom Lynch is Assistant Editor – Imaging, and is a Radiologist and Lead Nuclear Medicine Physician in the Northern Ireland Cancer Centre based at the Belfast City Hospital. Tom specialises in PET/CT scanning and nuclear medicine with a special interest in paediatric nuclear medicine. Dr Heidi Sowter is Assistant Editor – Web Review, and is a Lecturer in Forensic Science and Biology, at the Faculty of Education, Health and Science, University of Derby. Heidi continues to pursue her research interests in gynaecological and breast cancer. Ms Kathleen Mais is Assistant Editor – Nursing, and is a Nurse Clinician in Head & Neck Oncology at Christie Hospital, Manchester. Kathleen qualified as a nurse in Newcastle-upon- Tyne. Kathleen is a nurse-prescriber and runs a nurse-led chemotherapy clinic as well as continuing her work in clinical research. Michael Douek is Assistant Editor – Breast, and is a Senior Lecturer and Consultant Surgeon at University College London Hospitals focusing on breast cancer surgery with a particular interest in pre-operative surgical planning using breast MRI. In 2003, he was awarded a prestigious Health Foundation Clinician Scientist grant by the UK Academy of Medical Sciences, fully funding his joint academic and clinical post in breast surgery. Alan Cooper is Assistant Editor – Urology, and is Lead Scientist with the urology research group in Southampton University Hospitals and senior lecturer (albeit with virtually no lecturing burden) in the Department of Biomedical Sciences at Portsmouth University. Marilena Loizidou is Assistant Editor – Colorectal, and is a Non-Clinical Senior Lecturer in the Department of Surgery, UCL. Her research program focuses on aspects of colorectal cancer and liver metastases, from the basic underlying biology to new potential treatments. The current focus of research is the contribution of the peptide endothelin-1 to tumour growth and progression in the bowel. Additional research areas include breast and bladder cancer. Dr S Gokul is Assistant Editor - Journal Reviews, and is a Consultant Medical Oncologist at The James Cook University Hospital, Middlesbrough. His areas of interest are lung and gynaecological cancers. Helen Evans is a Journal Reviewer for Oncology News. Helen recently worked as a Senior Lecturer in Cancer Nursing at the Institute of Nursing and Midwifery, University of Brighton but following the birth of her son has returned to clinical practice as a Clinical Nurse Specialist at St. Wilfrid's Hospice in Chichester. Meet the Editorial Team BioMedES Producing the very best definitive versions of your biomedical reports and papers Never heard of us? Not surprising, since our operations are mostly ‘behind the scenes’. But we may be able to help you with your publication problems, from technical notes to e-books! What does BioMedES do? • BioMedES reworks sound scientific papers, technical reports, and other (biomedical) documents, putting them into the most idiomatic English that passes the most stringent peer review and quality control assessments • It copy edits for a number of big biomedical publishing houses • Four journals in the life sciences are run from, or with the aid of, the company • It helps administer an international organisation for cell biology (www.ifcbiol.org) • It prepares and publishes e-books in biomedicine • It designs logos for biomedical and many other organisations • It collates and prepares abstracts for scientific and other meetings • The company is involved in arranging both national and international conferences. • It also runs courses on scientific and medical writing, and on electronic publishing Why not contact us at: BioMedES, Leggat House, Keithhall, Inverurie, AB51 0LX, UK Tel: +44-1467-670280; Fax: +44-1467-629123 • Email: wheatley@abdn.ac.uk; info@biomedes.co.uk
  4. 4. 4 Volume 3 Issue 2 • August/September 2008 T here is little doubt that some of the most serious cases of cancer are those that attack the lungs. If this is truly the main killer amongst the cancers in the UK, is not there a need for a great deal more research into this particular organ and its tumours? The provoking factors have been fairly obvious for years, and in one guise or another are largely attributable to pollution, being self-administered by those of us who continue to smoke tobacco. The lungs have an enormous area that is in immediate contact with the environment, an area which is far greater than that of the skin that covers the body. Lung tissue, in contrast to skin, is moist and extremely thin, with blood vessels intimately associated with the fine walls of the alveoli. How will the situation look in twenty to thirty years from now? If we assume that the effects of smoking will then be affecting only the more aged members of society who had smoked in the past, and far fewer young people will be progressing in the same way, are we going to see it become one of the least common forms of cancer. [With asbestos the same story should unfold as crocidolite is “phased out” and HSE make sure stringent measures are taken to avoid its inhalation by workers in future. We read earlier in ON (Oncology News 2008;4(2):9-11) that mesothelioma will wane in the same way.] The worrying sector at the present time is young women, who continue to smoke and will be at risk of lung cancer for perhaps at least two more generations. Since on average people are living considerably longer these days than 30 or 40 years ago, there is a high probability that sufficient time will elapse for the incidence of lung cancer to rise in this sub-population of women smokers. The problem is that lung cancer can sometime be asymptomatic, or sufferers are too reluctant to seek help that they do not present for so long that patients do not present with tumours until they are considerably advanced. If we screen for bowel and cervical cancer, the question of whether we can do so for lung cancer has already been addressed in the pages of ON. The treatments for lung cancer do not make for good reading - that is, for the sufferer. Life expectancy is low and there seems to be little that can be done to raise the expectation of life by even a short period of time. But in this issue, Espeed Khoshbin and Alan JB Kirk (p10), delve deeply into many of the approaches that can be taken, and emphasise a number of useful points. One is that, given the circumstances, palliative care has to be a priority so that good QOL is achieved in the short respite sufferers may have in their last months. And the delivery of good medicine centres these days on the MultiDisciplinary Team (MDT) that should meet regularly to review all such patients, making for the best possible management. The lung cancer patient needs this more than almost any other cancer patient, especially when bones and brain become affected by metastases. We discussed in a recent editorial the topic of permutations and combinations in the treatment of cancer, and this seems to be particularly pertinent in the case of lung cancer patients. Combinations of treatments that follow one another rather than necessarily being given at about the same time seem to be prevalent because much depends on which type of lung cancer it is, how large it is, whether it is in the local lymph nodes or more widespread, how much co-morbidity is involved, among other mitigating factors. On the last issue, smokers often have a high alcohol consumption, many have a poor diet, and most of them get little exercise - little wonder that their general health is considerably below average. It is also no wonder that patients have to be examined by a whole gamut of different techniques to assess their general state of health prior to surgery, chemotherapy and radiotherapy. Resection of lobes of the lung becomes less advisable when the sufferer has a poor cardiac condition. If done in the more robust patient, the loss of lung tissue puts an immediate stress on the patient, who may thereafter have to use oxygen as a support, or take on a much more sedentary life. The outlook for all lung cancer patients seems bleaker than for most other types of tumour. One would hope that, despite the improvement in the application of established techniques (better delivery of radiation, more specific chemotherapeutic agents, etc.) some new avenues would open in terms of lung cancer treatment. Are there any real grounds for believing that there might be some breakthrough which will provide an effective means of controlling lung cancer? Or do we stick to refining the ways in which the current modalities are administered, to optimise them and combine them using the most carefully devised strategies? If these are the issues before us, then what should be the focus of effort? The latter has to be done whether or not more basic research can find new methods of treatment, such as immunotherapy. Perhaps before basic research could add significantly in this way, it is probable that the tide of lung cancer we have seen through the 20th century and persisting into the first part of the 21st century will have receded, and less pressure will come to bear on getting a better understanding of the fundamental causes and cellular misbehaviour that leads to lung cancer. That leaves screening as the only option needing to be considered, (see John Field K and Duffy SW, Oncology News 2008;3(1):6-8), in which there seems to be little advance even for the most high risk groups. And yet lung cancer remains the most common cause of death amongst cancers in the UK. n Lung Cancer Continues to Occupy the Frame Denys Wheatley, Editor/ Editorial
  5. 5. Cytosafe® Tough, polypropylene vial developed to reduce the risk of breakage and leakage New 300mg vial Designed with the typical FOLFIRI regimen* in mind (based on average patient dose)1,2 Indicated for the treatment of patients with advanced colorectal cancer. See prescribing information for full indication. CAMPTO® (irinotecan hydrochloride trihydrate): PRESCRIBING INFORMATION – UK Please refer to the Summary of Product Characteristics (SmPC) before prescribing Campto 20mg/ml. Presentations: Vials of concentrate for infusion containing either 40mg, 100mg or 300mg irinotecan hydrochloride trihydrate. Indications: Treatment of adult patients with advanced colorectal cancer: in combination with 5-fluorouracil, folinic acid in patients without prior chemotherapy and as monotherapy in patients who have failed a 5-fluorouracil, folinic acid based therapy. Campto may be used in combination with cetuximab for the treatment of Epidermal Growth Factor Receptor-expressing metastatic colorectal cancer after failure of Campto-including cytotoxic therapy. Campto may be used in combination with 5-fluorouracil, folinic acid and bevacizumab for the treatment of metastatic carcinoma of the colon and rectum. Dosage & Administration: Campto should be administered as an intravenous infusion over 30 to 90 minutes. In first line: combination therapy of 180mg/m2 every 2 weeks followed by folinic acid and 5-fluorouracil. In second line: monotherapy 350mg/m2 every 3 weeks. In combination with cetuximab: Administer cetuximab first, do not administer Campto earlier than 1 hour after the end of cetuximab infusion. Refer to cetuximab product information for dosage. In combination with bevacizumab, refer to the bevacizumab product information for dosage. Prophylactic antiemetics are recommended. Dosage Adjustments: Subsequent cycles should follow appropriate recovery of all adverse events to grade 0 or 1 NCI-CTC and resolution of diarrhoea. Dose reduction of 15-20% recommended if patients experience significant haematological toxicity, thrombocytopenia and leucopenia (grade 4), and non-haematological toxicity (grade 3-4). Impaired hepatic function: Monitor liver function regularly. In monotherapy blood bilirubin levels (up to 3 times ULN) in patients with performance status ≤2, should determine the starting dose of Campto. No data are available in patients with hepatic impairment treated by Campto in combination. Impaired renal function: Not recommended. Elderly: Care due to the greater frequency of decreased biological functions. Contraindications: Chronic inflammatory bowel disease and/or bowel obstruction; severe hypersensitivity reactions to Campto; pregnancy; breastfeeding; bilirubin >3 ULN; severe bone marrow failure; WHO performance status >2, concomitant use of St John’s Wort. Refer to cetuximab or bevacizumab product information for contraindications. Warnings and Precautions: Use in units specialised in the administration of cytotoxic chemotherapy. Patients should be aware of the risk of delayed diarrhoea (occurring >24 hours after the infusion). Loperamide is the recommended treatment, but should not be given prophylactically. Weekly monitoring of full blood counts recommended. Regular liver function tests should be performed. Prophylactic treatment with antiemetics is recommended. Cases of acute cholinergic syndrome should be treated with atropine. Risk factors for the development of pulmonary infiltrates should be considered. Patients should not drive if dizziness or visual disturbances occur. Women of childbearing age receiving Campto should be advised to avoid becoming pregnant. Interactions: Avoid concomitant use with CYP34A inducers or inhibitors. Care in patients receiving neuromuscular blocking agents. St John’s Wort should not be administered with Campto. SN38 (the active metabolite of Campto) concentrations were increased by 33% when combined with bevacizumab. Patients developing severe diarrhoea, leucopenia or neutropenia in combination with bevacizumab should have Campto dose modification. Adverse Reactions: Delayed diarrhoea (requires immediate treatment with loperamide). Nausea and vomiting, dehydration, neutropenia, fever, acute cholinergic syndrome, dyspnoea, asthenia, reversible alopecia. Infrequently dehydration-related renal insufficiency, hypotension or circulatory failure. Other system disorders include gastrointestinal, blood, infection and infestation, general disorders and infusion site reactions, cardiac, respiratory, skin and subcutaneous tissue, immune system, musculoskeletal, and nervous system. Refer to the relevant product information for details on adverse reactions that may occur when used in combination with cetuximab or bevacizumab. Pharmaceutical Precautions: Solution must be prepared aseptically. Do not mix with other medications. The solution should be used immediately after reconstitution, as it contains no antibacterial preservative. Dilute with infusion solution (0.9% sodium chloride or 5% glucose solution). Protect from light. Comply with prevailing cytotoxic handling guidelines when preparing or handling Campto. Legal category: POM. Basic NHS Price: Vials: Campto 40mg; £53.00; Campto 100mg; £130.00; Campto 300mg; £390.00. Marketing Authorisation Number: 40mg: PL 00057/0626, 100mg & 300mg PL 00057/0627. Marketing Authorisation Holder: Pfizer Limited, Sandwich, Kent, CT13 9NJ, United Kingdom. Date of Revision: February 2008 (REF: CF 5_0). References: 1. Mosteller RD. N Engl J Med 1987;371:1098. 2. Campto® Summary of Product Characteristics, February 2008. 3. Tournigand C et al. J Clin Oncol 2004;22:229-237. *FOLFIRI – irinotecan 180mg/m2 given as a 90-minute infusion and leucovorin 200mg/m2 as a 2-hour infusion, followed by bolus FU 400mg/m2 and a 46-hour infusion FU 2,400mg/m2 for two cycles, increased to 3,000mg/m2 from cycle 3 in case of no toxicity greater than grade 1 during the two first cycles. Repeated every 2 weeks.3 CAM08/019a Further information is available on request from: Medical Information at Pfizer Limited, Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK. Tel: +44 (0) 1304 616161 Adverse events should be reported to Pfizer Medical Information on 01304 616161. Information about adverse event reporting can also be found at www.yellowcard.gov.uk Plan for living Campto® now in CytoSafe® 300mg Vials shown not actual size 100mg40mg PFZ07JO8009_Oncology_News_210x297:PFZ07JO8009_Oncology_News_210x297 2/6/08 12:23 Page 1
  6. 6. 6 Volume 3 Issue 2 • August/September 2008 Contents Volume 3 Number 2 August/September 2008 Copyright: All rights reserved; no part of this publica- tion may be reproduced, stored in a retrieval system or transmitted in any form or by any means, elec- tronic, mechanical, photocopying, recording or other- wise without either the prior written permission of the publisher or a license permitting restricted photo- copying issued in the UK by the Copyright Licensing Authority. Disclaimer: The publisher, the authors and editors accept no responsibility for loss incurred by any person acting or refraining from action as a result of material in or omitted from this magazine. Any new methods and techniques described involving drug usage should be followed only in conjunction with drug manufacturers' own published literature. This is an independent publication - none of those con- tributing are in any way supported or remunerated by any of the companies advertising in it, unless other- wise clearly stated. Comments expressed in editorial are those of the author(s) and are not necessarily endorsed by the editor, editorial board or publisher. The editor's decision is final and no correspondence will be entered into. 3 Editorial Board 4 Editorial 8 What is UCAN? Catherine Paterson, Sam McClinton, Aberdeen, UK. 10 Management of Primary Lung Cancer Espeed Khoshbin, Alan JB Kirk, Clydebank, UK. 14 Upper GI Oncology Section - The Current Treatment of GIST With Reference to Laparoscopic Resection and Neoadjuvant Treatment Siobhan Gill, Paras Jethwa, Surrey, UK. 18 Urological Cancer Section – Prostate Cancer Reviewed: Part 2 Treatment Options Simon Mackie and Bhavan Rai, Aberdeen, UK. 20 Book Reviews 21 Conference News Previews and reports from the conference scene. 26 Imaging Section – Introduction to the use of MRI in Staging of Rectal Cancer K Lowry, A Armstrong, T Lynch, E Napier, Belfast, UK. 28 Diary Listing of meetings, courses and conferences, both UK and international. 29 Courses & Conferences 32 Web Review Heidi Sowter, Derby, UK. 33 Society News ECCO-ESMO Collaboration 12 & 34 News Update Details of the latest developments and news from the industry and charities. Oncology News is published by McDonnell Mackie, 84 Camderry Road, Dromore, Co Tyrone, BT78 3AT, N Ireland. Publisher: Patricia McDonnell • Web: www.oncologynews.biz Advertising and Editorial Manager: Patricia McDonnell Tel/Fax: +44 (0)288 289 7023 • Email: Patricia@oncologynews.biz Advertising and Press Releases: Grant Mackie Email: Grant@oncologynews.biz Design & Production Email: design.dept@sky.com Printed by: Warners Midlands PLC Tel: 01778 391000 Copyright: All rights reserved; no part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electron- ic, mechanical, photocopying, recording or otherwise without either the prior writ- ten permission of the publisher or a license permitting restricted photocopying issued in the UK by the Copyright Licensing Authority. Disclaimer: The publisher, the authors and editors accept no responsibility for loss incurred by any person acting or refraining from action as a result of material in or omitted from this mag- azine. Any new methods and techniques described involving drug usage should be followed only in conjunction with drug manufacturers' own published litera- ture. This is an independent publication - none of those contributing are in any way supported or remunerated by any of the companies advertising in it, unless otherwise clearly stated. Comments expressed in editorial are those of the author(s) and are not necessarily endorsed by the editor, editorial board or pub- lisher. The editor's decision is final and no correspondence will be entered into. Oncology What is UCAN? Management of Primary Lung Cancer The Current Treatment of GIST With Reference to Laparoscopic Resection and Neoadjuvant Treatment Prostate Cancer reviewed: Part 2 - Treatment Options News Volume 3 Issue 2 :August/September 2008 www.oncologynews.biz In this issue ISSN 1751-4975 Cover picture: Stockholm Clock Tower by Andrew Conn. 8 Volume 3 Issue 2 • August/September 2008 U CAN is a charitable company set up to improve the quality of life for people and families living with urological cancers in the North of Scotland. Urological cancers, (kidney, prostate, bladder, testicular and penile) are among the most common types of cancers. They account for one in three of all cancers in men and one in five of all cancers in men and women. UCAN was launched in January 2006 by Mr Sam McClinton and Professor James N’Dow, two consultant urological surgeons based at the Aberdeen Royal Infirmary. They created UCAN as a direct result of cancer sufferers, families and health professionals identifying a need to provide additional and improved services which are not, and cannot be, provided under the statutory duties of the NHS. There exists a stigma associated with urological cancers. Quite often patients seek medical advice from their doctor at a point when it is too late to offer curative treatment. Those who have been diagnosed with a urological cancer often suffer long-term social, emotional and psychological problems. Sufferers frequently struggle to come to terms with the trauma of urological cancer and the potentially life-changing effects of treatment, such as urostomy and erectile dysfunction. Long-term psychological problems can affect sufferers’ partners and families as much as the patient themselves, significantly increasing the number of lives blighted by urological cancer. UCAN recognises that a significantly higher level of support is required for those diagnosed with urological cancer than is currently available. What does UCAN plan to achieve? Our plans are split into three main areas: • Improving early diagnosis and knowledge 1) Our awareness campaign has been running for two years. We need to raise the profile of urological cancers to the level of breast and bowel cancer, and educate individuals on the early signs of urological cancers, in a bid to reduce the mortality rates. We also want to take the stigma out of these illnesses which by their nature can cause embarrassment. 2) One of our key challenges is to get men to take responsibility for their own health to the same degree as women. We are working with employers to help get our messages across in the workplace. Early diagnosis of cancer would not only help the patient but also the employer through reduced time off work. • Building effective support structures 1) There is a desperate need to provide patients and families with new avenues of support to help them adjust to, and live with, the changes a cancer diagnosis might bring to their lives. On occasions, the need will be for human contact; on other occasions the need might be for relative anonymity through online contact. 2) We recognised the need for a central hub close to the clinical services. A new Urological Cancer Care Centre was opened in January 2008, in the department of urology and is already fully operational providing practical support to cancer sufferers. 3) An important element of building effective support structures will be the Plain English Guides which will convert a vast amount of unregulated information into short, easily understood documents, with the facts a cancer patient needs to know. • Acquired knowledge and research 1) By researching the knowledge and experience of urology cancer patients, their families and clinicians worldwide, we will be able to determine what information cancer sufferers need at different stages of treatment. The family unit also needs information as they are affected just as much as the cancer sufferers. This information is vital when deciding which treatment to choose if the cancer sufferer is not to regret that decision at a later date. It is also very important to discover the best ways of managing the often unpleasant effects of treatments. What makes UCAN unique? Our activities are distinctive in the following ways: • Projects are developed in partnership with the beneficiaries; allowing us the best chance of being relevant to urological cancer sufferers and their families. What is UCAN? Catherine Paterson, UCAN Research Nurse, Academic Urology, University of Aberdeen, Health Sciences Building, Aberdeen. Sam McClinton, Consultant Urological Surgeon, Aberdeen Royal Infirmary Correspondence to: Catherine Paterson, UCAN/Total Research Nurse, OTIS Study Co-ordinator, UCAN/Academic Urology, 1st Floor Health Sciences Building, Foresterhill, Aberdeen, AB25 2ZD, UK. A Urological CANcer is diagnosed every 10 minutes 10 Volume 3 Issue 2 • August/September 2008 L ung cancer is one of the most common cancers in the Western world, with around 38,000 patients being diagnosed each year in the UK. Rarely diagnosed in the under 40s, lung cancer is a disease of the late middle-aged and elderly. Peak incidence is in the 75-84 age-group, with 85% of patients being over the age of 60 (Figure 1). In the 1950s, the sex ratio was M:F 6:1; with reducing incidence in males and increasing rates in females, wth the current sex ratio being nearly 7:5. Cigarette smoking is linked to lung cancer in well over 90% of cases, although other environmental causes such as asbestos and radon gas exposure have been implicated. Lung cancer is the leading cause of death from cancer in the UK, 22% of all cancer deaths being attributable to lung cancer. The current 5-year survival for lung cancer in the UK is 7% [1]. Types of lung cancer There are two broad groups of lung cancer defined by their histological appearance [2]. These are Small Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC). SCLC and NSCLC differ in a number of ways; their cell origin is different, SCLC being neuroendocrine, whereas NSCLC is epithelial. SCLC is very chemosensitive, but NSCLC is less so. SCLC is generally metastatic at presentation, whereas NSCLC may initially be locoregional. SCLC is generally not a surgical disease, while NSCLC may be resectable. Examples of individual types of NSCLC are squamous, adenocarcinoma and large cell carcinoma. The key to current treatment of patients with lung cancer is the multidisciplinary team (MDT) [3]. The workings and membership of the MDT vary from region to region. MDT meetings should ideally be held weekly and attended by all the major players (Table 1). All patients with lung cancer should be reviewed, the object being to deliver the best possible treatment to each patient depending on their tumour stage and state of health. SCLC treatment Patients with SCLC are categorised as either with limited disease (LD), where the disease is confined to the thorax, or extensive disease (ED), where there is evidence of distant metastases [4]. Patients with ED are generally given chemotherapy, designed to produce palliation and shrinkage of the tumour burden. About 50% of patients with SCLC that are in the ED category will have clinical or subclinical cerebral metastases. For this reason, prophylactic cranial irradiation (PCI) is often administered [5]. SCL cases categorised as LD also get chemotherapy. Where there is a complete or good response, mediastinal radiotherapy +/- PCI is considered for survival advantage and improved quality of life [6]. There will be a small group of patients who present with early disease. Under these circumstances, if properly staged, surgery may have a role. NSCLC treatment Key to the management of patients with NSCLC is TNM staging of the tumour, which is based on tumour characteristics (T), nodal involvement (N), and the presence or absence of metastases (M). A summary of lung cancer TNM is given in Table 2. However this classification is being reassessed and updated; the update will be published later in 2008 [7]. Management of Primary Lung Cancer Espeed Khoshbin Registrar in Cardiothoracic Surgery. Alan JB Kirk, Consultant Thoracic & Cardiac Surgeon. Correspondence to: Department of Thoracic Surgery, West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital, Clydebank, UK. Email: khoshbinuk@ yahoo.co.uk Source: Cancer Research UK Table 1: Key members of the MDT Chest physician Lung Cancer Nurse Specialist Thoracic Surgeon Oncologist (Clinical +/- Medical) Palliative Care Physician and/or nurse Chest radiologist Lung Pathologist Secretarial support and/or MDT coordinator Lung cancer audit staff Primary Care representative 14 Volume 3 Issue 2 • August/September 2008 The Current Treatment of GIST With Reference to Laparoscopic Resection and Neoadjuvant Treatment Miss Siobhan Gill, MRCS, Senior House Officer in Surgery. Mr Paras Jethwa, BSc (Hons), MD, FRCS(Gen), Consultant General & Upper GI Surgeon. Correspondence: P Jethwa, Surrey & Sussex NHS Trust, Dept of Surgery, Canada Avenue, REDHILL, Surrey, RH1 5RH, UK. Upper GI Oncology G astrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the alimentary tract; they account for <1% of all GI malignancies with approximately 900 new cases per year in UK [1]; primary GISTs tend to arise as solitary lesions most commonly affecting the stomach (60-70%), followed by the small bowel (20- 25%) and less commonly the rectum, oesophagus and colon [2]. Genetic analysis has revised the definition of GIST to be that of “highly cellular mesenchymal tumours of the gastrointestinal tract containing spindle, epitheloid cells or a combination of both and displaying CD117/c- kit positivity”. GISTs have been proposed to originate from the interstitial cells of Cajal, considered to be regulators of gastrointestinal motility but, as they can arise from tissue depleted of Cajal cells, the possibility that they arise from a pluripotent stem cell has been suggested [3]. The management of GISTs has evolved rapidly with our understanding of the molecular pathophysiology of this lesion allowing for the rational development of antitumour agents that target signalling aberrations in these cells. Imatinib mesylate (Gleevac, Glivec), a tyrosine kinase and platelet derived growth factor receptor (PDGR) antagonist, have shown excellent results in patients with unresectable or metastatic GIST, but surgical resection of the primary tumour remains the treatment of choice when cure is sought. There is, however, still debate regarding the most appropriate operative approach and the extent of resection required. While metastatic spread is common at first diagnosis, spread to lymph nodes is rarely seen thus, more extensive resection other than the primary site is questionable and has no bearing on survival or recurrence. Recently the National Comprehensive Cancer Network (NCCN) task force reported that “laparoscopic or laparoscopic-assisted resection may be useful for small (<2cm) GISTs when the risk of intraoperative tumour rupture is low. However, the use of laparoscopic resection is generally discouraged for GIST” [4]; despite this, laparoscopic resection of primary GIST has become the treatment of choice in many centres in the UK and Europe. This article summarises the current role of surgery and targeted chemotherapy in the management of GISTs. Minimally invasive surgery for GIST Laparoscopic surgery for gastrointestinal cancer and, more recently gastric cancer has been widely adopted in Japan, Korea, China, Italy, USA and the UK, but not without some debate. Unlike adenocarcinoma, lymphadenectomy is unnecessary with the aim of GIST surgery being the complete removal (R0) of the tumour with negative resection margins and without capsule rupture or intra-abdominal spillage of 8 10 14
  7. 7. Date of Preparation: December 2007 1030/10216 Prescribing Information for Innohep® 20,000 IU/ml and Innohep® Syringe 20,000 IU/ml Presentations: Innohep® 20,000 IU/ml contains tinzaparin sodium 40,000 anti-Factor Xa IU in a 2ml vial with preservative. Innohep® Syringe 20,000 IU/ml contains tinzaparin sodium 20,000 anti- Factor Xa IU/ml without preservative. The syringes contain 10,000 anti-Factor Xa IU in 0.5ml, 14,000 anti-Factor Xa IU in 0.7ml or 18,000 anti-Factor Xa IU in 0.9ml. Indications: Treatment of deep vein thrombosis and of pulmonary embolus. Dosage and Administration: Subcutaneous injection only. Adults: 175 anti-Factor Xa IU/kg bodyweight once daily for at least 6 days and until adequate oral anti-coagulation is established. There is no need to monitor the anticoagulant activity of Innohep® . Use in Children: No experience. Contra-Indications: Known hypersensitivity to constituents. Generalised haemorrhagic tendency, uncontrolled severe hypertension, active peptic ulcer, septic endocarditis. Thrombocytopenia in patients with a positive in vitro aggregation test in the presence of tinzaparin. Locoregional anaesthesia in elective surgical procedures. Precautions: Care in patients with severe liver or kidney insufficiency, a dose reduction should be considered. Do not give by intramuscular injection (risk of haematoma). Caution in patients with a history of asthma (presence of sodium bisulphite). Care in patients who have recently suffered from cerebral haemorrhage, trauma and/or had recent surgery to the central nervous system. Caution in patients with hypersensitivity to heparin or to other low molecular weight heparins. For some patients with pulmonary embolism (e.g. those with severe haemodynamic instability) alternative treatment, such as surgery or thrombolysis may be indicated. Heparin can lead to hyperkalaemia, particularly in patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium or taking potassium-sparing drugs. The risk appears to increase with duration of therapy but it is usually reversible. Measure plasma potassium in patients at risk before starting therapy and monitor regularly. In patients undergoing spinal/peridural anaesthesia or spinal puncture, the prophylactic use of heparin may be very rarely associated with epidural/spinal haematoma resulting in prolonged or permanent paralysis. Risk is increased by use of peridural/spinal catheter, drugs affecting haemostasis and traumatic/repeated puncture. Extreme vigilance and frequent monitoring are required. Platelet counts should be measured in patients receiving heparin for longer than 5 days (risk of thrombocytopenia). Stop treatment immediately in those who develop thrombocytopenia. Not recommended for use in patients with prosthetic heart valves. Drug Interactions: Any drug which affects platelet function or aggregation or blood coagulation should be used with caution. Pregnancy and Lactation: Do not use in pregnancy unless no safer alternative is available. Not recommended for use in pregnant women with prosthetic heart valves. It is not known whether Innohep® is excreted in breast milk. Stop breast-feeding while receiving Innohep® . Side Effects: Skin rashes and minor bruising at site of injection. Systemic allergic reactions have been reported extremely rarely. Innohep® , like heparin, has been shown to increase the risk of haemorrhage. However, at the recommended dose this risk is low. Thrombocytopenia may occur rarely. As for heparin, a transient rise in aminotransferase levels is frequently seen. Rarely, clinically significant hyperkalaemia may occur with heparin products particularly in patients with chronic renal failure and diabetes mellitus. Very rare cases of epidural/spinal haematoma have been reported in patients undergoing spinal or epidural anaesthesia or spinal puncture while receiving heparin prophylaxis. Skin necrosis has been reported. If this occurs withdraw treatment immediately. Priapism has been reported rarely. Valve thrombosis in patients with prosthetic heart valves have been reported rarely. Legal Category: POM Product Licence Numbers and Holder: Innohep® 20,000 IU/ml – PL 0043/0192, Innohep® Syringe 20,000 IU/ml – PL 0043/0197. LEO Laboratories Limited, Longwick Road, Princes Risborough, Bucks. Basic NHS Price: Innohep® 20,000 IU/ml (40,000 anti- Factor Xa IU vial, 2ml) x 1, £34.20. Innohep® Syringe 20,000 IU/ml, 0.5ml x 2, £17.95. 0.5ml x 6, £53.85. 0.7ml x 2, £25.14. 0.7ml x 6, £75.40. 0.9ml x 2, £32.31. 0.9ml x 6, £96.93. Last revised: January 2006. Further information can be found in the Summary of Product Characteristics or from: LEO Pharma, Longwick Road, Princes Risborough, Buckinghamshire, HP27 9RR. If you wish to report an adverse event, this can be done either by contacting Drug Safety at LEO Pharma (01844 347333) or by logging on to www.yellowcard.gov.uk. ® Registered Trademark e-mail: Innohep.UKenquiries@leo-pharma.com tinzaparin sodium *innohep® - giving more life to patients with pulmonary embolism You’re fighting cancer - Don’t be beaten by a PE 1. Hull RD et al. Am J Med 2006; 119:1062-1072 innohep® - long term efficacy in treatment of PE and DVT in cancer patients1 LEO® ©LEO,LEOPharma,UK,December2007,ALLLEOTRADEMARKSMENTIONEDBELONGTOTHELEOGROUP
  8. 8. 8 Volume 3 Issue 2 • August/September 2008 U CAN is a charitable company set up to improve the quality of life for people and families living with urological cancers in the North of Scotland. Urological cancers, (kidney, prostate, bladder, testicular and penile) are among the most common types of cancers. They account for one in three of all cancers in men and one in five of all cancers in men and women. UCAN was launched in January 2006 by Mr Sam McClinton and Professor James N’Dow, two consultant urological surgeons based at the Aberdeen Royal Infirmary. They created UCAN as a direct result of cancer sufferers, families and health professionals identifying a need to provide additional and improved services which are not, and cannot be, provided under the statutory duties of the NHS. There exists a stigma associated with urological cancers. Quite often patients seek medical advice from their doctor at a point when it is too late to offer curative treatment. Those who have been diagnosed with a urological cancer often suffer long-term social, emotional and psychological problems. Sufferers frequently struggle to come to terms with the trauma of urological cancer and the potentially life-changing effects of treatment, such as urostomy and erectile dysfunction. Long-term psychological problems can affect sufferers’ partners and families as much as the patient themselves, significantly increasing the number of lives blighted by urological cancer. UCAN recognises that a significantly higher level of support is required for those diagnosed with urological cancer than is currently available. What does UCAN plan to achieve? Our plans are split into three main areas: • Improving early diagnosis and knowledge 1) Our awareness campaign has been running for two years. We need to raise the profile of urological cancers to the level of breast and bowel cancer, and educate individuals on the early signs of urological cancers, in a bid to reduce the mortality rates. We also want to take the stigma out of these illnesses which by their nature can cause embarrassment. 2) One of our key challenges is to get men to take responsibility for their own health to the same degree as women. We are working with employers to help get our messages across in the workplace. Early diagnosis of cancer would not only help the patient but also the employer through reduced time off work. • Building effective support structures 1) There is a desperate need to provide patients and families with new avenues of support to help them adjust to, and live with, the changes a cancer diagnosis might bring to their lives. On occasions, the need will be for human contact; on other occasions the need might be for relative anonymity through online contact. 2) We recognised the need for a central hub close to the clinical services. A new Urological Cancer Care Centre was opened in January 2008, in the department of urology and is already fully operational providing practical support to cancer sufferers. 3) An important element of building effective support structures will be the Plain English Guides which will convert a vast amount of unregulated information into short, easily understood documents, with the facts a cancer patient needs to know. • Acquired knowledge and research 1) By researching the knowledge and experience of urology cancer patients, their families and clinicians worldwide, we will be able to determine what information cancer sufferers need at different stages of treatment. The family unit also needs information as they are affected just as much as the cancer sufferers. This information is vital when deciding which treatment to choose if the cancer sufferer is not to regret that decision at a later date. It is also very important to discover the best ways of managing the often unpleasant effects of treatments. What makes UCAN unique? Our activities are distinctive in the following ways: • Projects are developed in partnership with the beneficiaries; allowing us the best chance of being relevant to urological cancer sufferers and their families. What is UCAN? Catherine Paterson, UCAN Research Nurse, Academic Urology, University of Aberdeen, Health Sciences Building, Aberdeen. Sam McClinton, Consultant Urological Surgeon, Aberdeen Royal Infirmary Correspondence to: Catherine Paterson, UCAN/Total Research Nurse, OTIS Study Co-ordinator, UCAN/Academic Urology, 1st Floor Health Sciences Building, Foresterhill, Aberdeen, AB25 2ZD, UK. A Urological CANcer is diagnosed every 10 minutes
  9. 9. Volume 3 Issue 2 • August/September 2008 9 • The development of a comprehensive peer support framework is novel. It entails one-to-one mentoring by other urological sufferers, web based forum support by other sufferers and a world class cancer care centre, supported by skilled personnel, experts in the field of urology. The centre will also be backed by international collaboration, with the experience and expertise necessary for studying the information needs of urological cancer sufferers. • We are proposing not only support for urological cancer sufferers, but the family unit as a whole because we recognise that the impact of a cancer diagnosis and treatment is more far-reaching than just the person with the cancer. The project has the potential to benefit cancer sufferers and their families nationally and internationally. • In addition, specific groups in society will be targeted, such as young men who are traditionally reluctant to address their medical needs. A key emphasis is on prevention and early diagnosis that will limit the effects of these cancers and promote a speedy and full recovery. It is hoped that wider knowledge about these cancers will reduce the social stigma often associated with these illnesses. How our make-up and direction differs from other charities Our work is overseen by an independent UCAN Steering Committee that advises the UCAN Board of Directors. The committee chair, and half of the members, are urological cancer sufferers. Through the UCAN Steering committee, patients will continue to be at the centre of decisions about the activities of the charity. We also have a UCAN Patient Advisory Group (individuals who have had a urological cancer) who independently advises the clinical urology team and the direction of the support services for patients and their families. UCAN in Progress Buddy Network UCAN has recently launched its Buddy Network in partnership with NHS Grampian. The Buddy Network allows cancer patients to seek additional support from other patients as their advisors, who of course have been through a similar treatment experience. This support network allows patients to seek out further emotional support and practical advice from other individuals who have had a similar treatment journey. This is a very distinct support network from the NHS, and unique for patients as it allows an opportunity for newly diagnosed cancer patients to verbalise their concerns and ask questions without the worry about how their loved ones are feeling. We currently have a cohort of patient advisors waiting to be a buddy for a newly diagnosed cancer patient. Progress so far is positive and certainly a valued aspect of patients’ treatment packages. Forum The UCAN online forum was launched in April 2007; this support service is moderated by the patients with an overview from the medical team. Within the forum, we have a general area and cancer restricted areas (individual urological cancers to which only those who have had this cancer can gain access). From our pilot work, we found that this online support service is not only valuable for emotional support, but is an area where practical information, questions and experiences can be shared by patients anonymously. These support services can be accessed in our Urological Care Centre, as shown in the following picture. Health Education TOTAL E&P UK Limited has generously sponsored the UCAN Research Nurse, Catherine Paterson for three years. The North East of Scotland is the oil capital of Europe, with the oil industry being largely a male dominated work force. Consequently, our UCAN nurse has taken the health educational programme to the offshore oil rigs to target mens’ knowledge and attitudes towards the early signs of urological cancers. Since UCAN had endeavoured into this new venture, feedback has proved that this is a success and certainly helps to empower men to take ownership for their health. In line with the health educational programme part our aim to try to combat the stigma attached to these cancers. First Group have helped UCAN to achieve this by a risqué, yet very effective, way of capturing the attention of the general public in the north east of Scotland. n UCAN is working hard to get a handle on urological cancers, for more information please contact; UCAN office, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK. Website: www.ucanhelp.org.uk Email: ucan@abdn.ac.uk Telephone: 01224 559312. UCAN Research Nurse Offshore.
  10. 10. 10 Volume 3 Issue 2 • August/September 2008 L ung cancer is one of the most common cancers in the Western world, with around 38,000 patients being diagnosed each year in the UK. Rarely diagnosed in the under 40s, lung cancer is a disease of the late middle-aged and elderly. Peak incidence is in the 75-84 age-group, with 85% of patients being over the age of 60 (Figure 1). In the 1950s, the sex ratio was M:F 6:1; with reducing incidence in males and increasing rates in females, wth the current sex ratio being nearly 7:5. Cigarette smoking is linked to lung cancer in well over 90% of cases, although other environmental causes such as asbestos and radon gas exposure have been implicated. Lung cancer is the leading cause of death from cancer in the UK, 22% of all cancer deaths being attributable to lung cancer. The current 5-year survival for lung cancer in the UK is 7% [1]. Types of lung cancer There are two broad groups of lung cancer defined by their histological appearance [2]. These are Small Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC). SCLC and NSCLC differ in a number of ways; their cell origin is different, SCLC being neuroendocrine, whereas NSCLC is epithelial. SCLC is very chemosensitive, but NSCLC is less so. SCLC is generally metastatic at presentation, whereas NSCLC may initially be locoregional. SCLC is generally not a surgical disease, while NSCLC may be resectable. Examples of individual types of NSCLC are squamous, adenocarcinoma and large cell carcinoma. The key to current treatment of patients with lung cancer is the multidisciplinary team (MDT) [3]. The workings and membership of the MDT vary from region to region. MDT meetings should ideally be held weekly and attended by all the major players (Table 1). All patients with lung cancer should be reviewed, the object being to deliver the best possible treatment to each patient depending on their tumour stage and state of health. SCLC treatment Patients with SCLC are categorised as either with limited disease (LD), where the disease is confined to the thorax, or extensive disease (ED), where there is evidence of distant metastases [4]. Patients with ED are generally given chemotherapy, designed to produce palliation and shrinkage of the tumour burden. About 50% of patients with SCLC that are in the ED category will have clinical or subclinical cerebral metastases. For this reason, prophylactic cranial irradiation (PCI) is often administered [5]. SCL cases categorised as LD also get chemotherapy. Where there is a complete or good response, mediastinal radiotherapy +/- PCI is considered for survival advantage and improved quality of life [6]. There will be a small group of patients who present with early disease. Under these circumstances, if properly staged, surgery may have a role. NSCLC treatment Key to the management of patients with NSCLC is TNM staging of the tumour, which is based on tumour characteristics (T), nodal involvement (N), and the presence or absence of metastases (M). A summary of lung cancer TNM is given in Table 2. However this classification is being reassessed and updated; the update will be published later in 2008 [7]. Management of Primary Lung Cancer Espeed Khoshbin Registrar in Cardiothoracic Surgery. Alan JB Kirk, Consultant Thoracic & Cardiac Surgeon. Correspondence to: Department of Thoracic Surgery, West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital, Clydebank, UK. Email: khoshbinuk@ yahoo.co.uk Source: Cancer Research UK Table 1: Key members of the MDT Chest physician Lung Cancer Nurse Specialist Thoracic Surgeon Oncologist (Clinical +/- Medical) Palliative Care Physician and/or nurse Chest radiologist Lung Pathologist Secretarial support and/or MDT coordinator Lung cancer audit staff Primary Care representative
  11. 11. Volume 3 Issue 2 • August/September 2008 11 Treatment strategies Management of patients with NSCLC can be considered as either radical (ie with curative intent) or palliative. Radical treatment options These would include surgery, radical radiotherapy and multimodality options. Surgery It is fair to say that surgical resection of primary lung cancer is the mode of therapy most often and consistently associated with cure [8]. The key question at an MDT meeting should be “is this patient suitable for surgery?” If not, the reasons should be documented. Indications for surgery can be subdivided into oncological and medical indications. Oncological considerations: All patients being considered for lung resection have the following investigations performed to stage the disease: chest X-ray, bronchoscopy, CT thorax, and PET/CT scan [9]. In certain circumstances other imaging may be required, eg CT or MR brain scan, isotope bone scan, liver ultrasound. Patients suitable for tumour resection will generally be those in whom the primary tumour is small, where it has not eroded into adjacent structures that would deem it irresectable, and where there is no (or minimal) lymph node spread and distant metastatic spread. Suitable tumour stages would be T1 and T2. Certain T3 tumours may be suitable for resection, such as local overlying rib invasion, where the tumour can be resected by lobectomy and en bloc chest wall resection. T4 tumours (eg where the tumour has infiltrated oesophagus, vertebral column or great vessels) are generally unresectable. Patients who are staged as N0 or N1 are generally suitable for lung resection provided everything else is favourable. If a patient is staged preoperatively as N2 (ipsilateral mediastinal nodes), surgery is not usually the best treatment. Pre- operatively staged N3 nodal disease would generally be a contraindication to surgery, outside a clinical trial. The presence of metastases would also be a contraindication to surgery. For example, a patient with hepatic, bony or adrenal metastases would certainly not be a suitable candidate for surgery. However, a small highly selected group of patients with solitary cerebral metastases and otherwise operable lung cancer might be treated by cerebral metastasectomy and lung resection, with survival benefit [10]. Medical considerations: Bearing in mind that these patients are generally elderly and have probably been cigarette smokers, many of them will have significant co- morbidities. Cardiac disease and COPD are often fellow- travellers, making careful clinical examination essential. Supportive laboratory tests are often required. Cardiac investigations should at a minimum be good clinical history and examination, with ECG. Further tests such as echocardiography, exercise ECG and cardiac catheterisation may be required. Respiratory assessment is clinical, lung function tests being essential. Surgical points If the PET scan shows evidence of FDG uptake in the mediastinum, mediastinoscopy is required for tissue diagnosis. However if the PET scan is negative in the mediastinum, no mediastinoscopy is necessary. Once the decision to operate has been made, the principles of surgery are to resect the tumour widely, leaving as much non-diseased functional lung as possible. In practice, lobectomy is the treatment of choice. This is certainly preferable to wedge resection or segmentectomy. Sometimes, however, lobectomy alone is insufficient to resect the cancer and bi-lobectomy or pneumonectomy is required. Operative mortality is 2-3% for lobectomy and ~7% for pneumonectomy. Long-term survival is dictated by the post- resection histology report. A 1cm T1 lesion with no nodal spread may have a 5-year survival in excess of 80%. A 5cm T2 tumour with resected N2 disease may have a 5 year survival of only 20%. For those patients who undergo a lung resection, their case should be discussed at a MDT meeting. In certain circumstances, adjuvant chemotherapy may be associated with survival advantage. Radical radiotherapy In certain circumstances with small tumours showing no evidence of nodal spread, the patient may not be suitable for surgery. Recent stroke, myocardial infarction or significant COPD may deem surgery inappropriate. In addition, small tumours that are thought to be inoperable may be better treated by radical radiotherapy [11]. With limited disease under these circumstances, radical radiotherapy may be associated with cure or extended survival. High dose radiotherapy (e.g. 60 Gy over four weeks on a daily basis) can be given. An improved form of radiotherapy called CHART Table 2: Lung Cancer TNM (summary) T1 Tumour less than or equal to 3cm in its greatest diameter T2 Tumour >3cm T3 Tumour invading local adjacent structure that can be easily resected eg chest wall diaphragm T4 Tumour invading adjacent structure that cannot be resected eg oesophagus, vertebra, aorta N0 No nodal spread N1 Involvement of local ipsilateral nodes within the envelope of the visceral pleura N2 Involvement of ipsilateral mediastinal nodes N3 Involvement of contralateral mediastinal nodes and/or isilateral/contralateral supraclavicular or scalene nodes M0 No evidence of distant metastases M1 Evidence of distant metastases
  12. 12. 12 Volume 3 Issue 2 • August/September 2008 (Continuous Hyperfractionated Accelerated Radiotherapy) is a 3-times daily treatment over about 12 days with no weekend breaks, giving improved survival (12). In certain circumstances chemotherapy can be administered in combination with radiotherapy to attempt to improve the results. Palliative therapy In advanced disease, it is accepted that cure is improbable. The management plan would be to reduce tumour bulk and provide the patient with as good a quality of life as possible. Radiotherapy is an excellent palliative therapy, and can provide relief from bony pain, irritating cough, haemoptysis and cerebral metastases [13]. Chemotherapy can also provide excellent palliation of symptoms and generally promote well- being, improve appetite and slow down weight loss [14]. Surgical procedures can provide palliation, such as pleurodesis of recalcitrant pleural effusions (Figure 2), disobliteration of airways with laser and stenting of oesophageal strictures secondary to mediastinal nodal involvement. These specific interventional measures are undertaken in addition to the general and specialist palliative care input that is provided at all stages of the progression of the disease in the patient, as is appropriate to their needs [15]. n Key points • Lung cancer is a common disease with generally a poor outcome; good results can be achieved in appropriately selected individuals • All patients with lung cancer should be reviewed by the Lung Cancer MDT and optimum treatment established • All patients in whom a radical option is being contemplated should have a CT scan of thorax and abdomen • All patients who might have radical treatment should have a PET scan References 1. Office of National Statistics. Cancer Statistics Registration: Registrations of cancer diagnosed in 2004, England, Series MBI no 33, 2005 2. WHO histological typing of lung cancers. In: International classification of tumours 2nd edition 1981, Geneva 3. Spira A, Ettinger DS. Multidisciplinary management of lung cancer. New England Journal of Medicine 2004;350:379-92. 4. Jackman DM, Johnson BE. Small-cell lung cancer. Lancet 2005;306:1385-96. 5. Prophylactic cranial irradiation in small-cell lung cancer: is it still controversial or is it a no-brainer? The Oncologist 2000;5:299-301. 6. Elias AD, Ayash L, Frei E et al. Intensive combined modality therapy for limited- stage small cell lung cancer. J Natl Cancer Inst 1993;85:559-66. 7. Goldstraw P, Crowley J, Chansky K et al. The IASCLC lung cancer staging project. Journal of Thoracic Oncology 2007;8:706-14. 8. Jablons D. Neoplasms of the lung. In: LW Way, GM Docherty (eds). Current Surgical Diagnosis & Treatment 11th ed: 395-407. 9. Shim SS, Lee KS, Byung-Tae K et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for pre-operative staging. Radiology 2005;236:1011-9. 10. Granone P, Margaritora S, D’Andrilli A, Cesario A, Kawamukai K, Meacci E. Non-small cell lung cancer with single brain metastasis: the role of surgical treatment. Eur J Cardiothorac Surg 2001;20:361-6. 11. Tyldesley S, Boyd C, Schulze K, Walker H, Mackillop WJ. Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach. Int J Radiat Oncol Biol Phys 2001;49:973-85. 12. Saunders MI. A randomised multicentre trial of CHART vs conventional radiotherapy in non-small cell lung cancer. Lung Cancer 1997;18:28-9. 13. Lester JF, Macbeth FR, Toy E, Coles B. Palliative radiotherapy regimens for non- small cell lung cancer. The Cochrane Database of Systematic Reviews 2006; issue3: Art no: CD 002143. 14. Tassivari D, Sartori S, Papi M et al. Outcomes of palliative care in stage IV non- small cell lung cancer. Have we found what we are looking for? Lung Cancer 2004;43:373-4. 15. Kvale PA, Selecky PA, Prakash, UBS. Palliative care in lung cancer. CHEST 2007;132:368-403. Figure 2: Malignant pleural effusion secondary to lung cancer. Reel Lives: The Cancer Chronicles Film Festival is the first ever international documentary film competition focused on cancer. It aims to raise awareness of the impact of cancer while also honouring people who have been touched by the disease. Reel Lives is produced by the International Union Against Cancer (UICC) and will be held in Geneva, Switzerland, on 28-30 August. The festival is supported by a grant from GlaxoSmithKline Oncology. In its inaugural year, the festival has already received more than 100 film entries from around the world, and has just added noted oncologist Dr. Larry Norton to its team of expert judges. “We are thrilled with the positive response,” says Isabel Mortara, executive director of UICC, the leading international non-governmental organization dedicated exclusively to the global control of cancer. “We believe the festival will help demystify cancer and deepen awareness of cancer as a pressing global health issue, while also highlighting progress in the fight against the disease.” The festival will take place during the 2008 World Cancer Congress in Geneva. The grand prize winner will receive $10,000. Other monetary prizes will also be awarded. For further information - www.reellives.org Contact: Claudia Durgnat, UICC/Reel Lives Film Festival Switzerland, Tel: +41 79 507 2324. Top Oncologist on Jury Panel
  13. 13. A lifeline in relapsed NSCLC Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.gov.uk. Adverse events should also be reported to Roche Products Limited. Please contact UK Drug Safety Centre on 01707 367554. J340678/JUL08 Prescribing Information Tarceva® (erlotinib) 25, 100 and 150 mg tablets Full prescribing information should be viewed prior to prescription. Indication: Treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. When prescribing, factors associated with prolonged survival should be taken into account. No survival benefit or other clinically relevant effects of the treatment have been demonstrated in patients with EGFR-negative tumours. Dosage and administration: The daily dose is 150 mg taken orally at least one hour before or two hours after the ingestion of food. When dose adjustment is necessary, reduce in 50 mg steps. Safety and efficacy of Tarceva in children has not been established. Contra-indications: Known hypersensitivity to erlotinib or any of the excipients. Precautions: Smokers should be advised to stop smoking as a clinically significant reduction in plasma concentration is likely. Interstitial lung disease (ILD), including fatalities, has been reported (incidence 0.6%). In patients who develop acute onset of new and/or progressive unexplained pulmonary symptoms such as dyspnoea, cough and fever, interrupt therapy pending diagnostic evaluation. If ILD is diagnosed, discontinue therapy and initiate appropriate treatment. Diarrhoea should be treated with loperamide. Tarceva dose reduction or interruption may be necessary in patients with severe or persistent diarrhoea. It may be necessary to intensively rehydrate the patient intravenously, monitor renal function and serum electrolytes including potassium. In patients with pre-existing liver disease or on concomitant hepatotoxic medications, periodic liver function testing should be considered. Tarceva dosing should be interrupted if changes in liver function are severe. As tablets contain lactose they should not be administered to patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Avoid concomitant administration with PPIs (Proton Pump Inhibitors), H2 antagonists and antacids (see Drug Interactions below). Drug Interactions: Plasma concentrations increase when combined with potent CYP3A4 inhibitors e.g. ketoconazole. It may therefore be necessary to reduce the dose of erlotinib. Potent CYP3A4 inducers e.g. rifampicin will decrease erlotinib plasma concentrations. Concomitant treatment should be avoided. If the combination cannot be avoided an increase in Tarceva dose to 300 mg can be considered, provided safety is closely monitored (renal/liver function and serum electrolytes). If well tolerated, after 2 weeks a further increase to 450 mg could be considered with continued monitoring. Caution should be observed in concomitant treatment with other CYP3A4 inducers. Significant interactions with the clearance of CYP3A4 substrates e.g. midazolam, erythromycin and paclitaxel, is unlikely. Potential interactions may occur with active substances which are metabolised by, or are inhibitors or inducers of CYP1A2, CYP1A1 and CYP1B1. Caution should be observed when ciprofloxacin or potent CYP1A2 inhibitors (e.g. fluvoxamine) are combined with erlotinib. Dose reduction may be required if an adverse event occurs. Monitor patients taking warfarin or other coumarin-derivative anticoagulants for changes in prothrombin time or international normalised ratio (INR). Concomitant administration of inhibitors of the P-glycoprotein active substance transporter e.g. cyclosporin and verapamil may lead to altered distribution and/or elimination of erlotinib. Solubility of erlotinib decreases at pH above 5. Drugs that alter the pH of the upper GI tract e.g. omeprazole (PPI) may alter the solubility of erlotinib and hence its bioavailability. Use with antacids and H2 antagonists should be avoided. If use of antacids is necessary take at least 4 hours before or 2 hours after erlotinib. Erlotinib increases platinum concentrations, though this is not considered to be clinically relevant. A study showed that carboplatin and paclitaxel did not affect erlotinib pharmacokinetics. Capecitabine may increase erlotinib concentrations but a clinical study showed there were no significant effects of erlotinib on the pharmacokinetics of capecitabine. Erlotinib and gemcitabine can be combined without significant effects on the pharmacokinetics. The inhibition of glucuronidation may cause interactions with medicinal products which are substrates of UGT1 A1 and exclusively cleared by this pathway. Pregnancy and lactation: There is no adequate experience in human pregnancy and lactation therefore Tarceva should only be used if the potential benefit justifies the potential risks. Women of childbearing potential must be advised to avoid pregnancy while on erlotinib and adequate contraceptive methods should be used during therapy, and for at least 2 weeks after completing therapy. Side effects and adverse reactions: See SmPC for full listing. Serious adverse reactions: Gastrointestinal: Cases of gastrointestinal bleeds have been commonly reported. Hepato-biliary disorders: Rare cases of hepatic failure (including fatalities) have been reported. Respiratory, thoracic and mediastinal disorders: Uncommon reports of serious interstitial lung disease (ILD), including fatalities. Infections and infestations: Severe infections, with or without neutropenia, have included pneumonia, sepsis and cellulitis. Common adverse reactions: Rash (75%), diarrhoea (54%), fatigue (52%) and anorexia (52%) were the most commonly reported adverse events in the BR.21 study. Most were grade 1/2 in severity and manageable without intervention. Diarrhoea can rarely lead to dehydration, hypokalemia and renal failure. Other adverse events reported, which occurred at a frequency ≥3% over placebo included pruritus, dry skin, nausea, vomiting, stomatitis, abdominal pain, dyspnoea, cough, infection, conjunctivitis and keratoconjunctivitis sicca. In the primary safety population the following was observed: Skin and subcutaneous disorders: Alopecia, paronychia, hirsutism, eyelash/eyebrow changes and brittle and loose nails. Hepato-biliary disorders: Liver function test abnormalities have been commonly observed. Most cases were mild or moderate in severity, transient in nature or associated with liver metastases. Eye disorders: Keratitis and corneal ulcerations. Respiratory, thoracic and mediastinal disorders: Epistaxis. Legal category: Presentations, Basic NHS Costs, and Marketing authorisation numbers: Tarceva (erlotinib) tablets 25 mg x 30: pack £378.33. EU/1/05/311/001. Tarceva (erlotinib) tablets 100 mg x 30: pack £1,324.14. EU/1/05/311/002. Tarceva (erlotinib) tablets 150 mg x 30: pack £1,631.53. EU/1/05/311/003. Marketing authorisation holder: Roche Registration Ltd, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. Tarceva is a registered trade mark. Date of preparation: January 2008. POM Journal:OncologyNewsRoche:TarcevaUKAd Size:297x210mmBleed:3mmSupplyashiresPDFJobno:XXXXX Tarceva UK Oncology News Ad 2008_XXXXX 28/7/08 11:13 Page 1
  14. 14. 14 Volume 3 Issue 2 • August/September 2008 The Current Treatment of GIST With Reference to Laparoscopic Resection and Neoadjuvant Treatment Miss Siobhan Gill, MRCS, Senior House Officer in Surgery. Mr Paras Jethwa, BSc (Hons), MD, FRCS(Gen), Consultant General & Upper GI Surgeon. Correspondence: P Jethwa, Surrey & Sussex NHS Trust, Dept of Surgery, Canada Avenue, REDHILL, Surrey, RH1 5RH, UK. Upper GI Oncology G astrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the alimentary tract; they account for <1% of all GI malignancies with approximately 900 new cases per year in UK [1]; primary GISTs tend to arise as solitary lesions most commonly affecting the stomach (60-70%), followed by the small bowel (20- 25%) and less commonly the rectum, oesophagus and colon [2]. Genetic analysis has revised the definition of GIST to be that of “highly cellular mesenchymal tumours of the gastrointestinal tract containing spindle, epitheloid cells or a combination of both and displaying CD117/c- kit positivity”. GISTs have been proposed to originate from the interstitial cells of Cajal, considered to be regulators of gastrointestinal motility but, as they can arise from tissue depleted of Cajal cells, the possibility that they arise from a pluripotent stem cell has been suggested [3]. The management of GISTs has evolved rapidly with our understanding of the molecular pathophysiology of this lesion allowing for the rational development of antitumour agents that target signalling aberrations in these cells. Imatinib mesylate (Gleevac, Glivec), a tyrosine kinase and platelet derived growth factor receptor (PDGR) antagonist, have shown excellent results in patients with unresectable or metastatic GIST, but surgical resection of the primary tumour remains the treatment of choice when cure is sought. There is, however, still debate regarding the most appropriate operative approach and the extent of resection required. While metastatic spread is common at first diagnosis, spread to lymph nodes is rarely seen thus, more extensive resection other than the primary site is questionable and has no bearing on survival or recurrence. Recently the National Comprehensive Cancer Network (NCCN) task force reported that “laparoscopic or laparoscopic-assisted resection may be useful for small (<2cm) GISTs when the risk of intraoperative tumour rupture is low. However, the use of laparoscopic resection is generally discouraged for GIST” [4]; despite this, laparoscopic resection of primary GIST has become the treatment of choice in many centres in the UK and Europe. This article summarises the current role of surgery and targeted chemotherapy in the management of GISTs. Minimally invasive surgery for GIST Laparoscopic surgery for gastrointestinal cancer and, more recently gastric cancer has been widely adopted in Japan, Korea, China, Italy, USA and the UK, but not without some debate. Unlike adenocarcinoma, lymphadenectomy is unnecessary with the aim of GIST surgery being the complete removal (R0) of the tumour with negative resection margins and without capsule rupture or intra-abdominal spillage of
  15. 15. Volume 3 Issue 2 • August/September 2008 15 tumour cells. Evidence has shown that survival is dependant on tumour size (<5cms), mitotic activity (<5/50 mitoses per high powered field), angiogenic upregulation and evidence of mutation rather than the extent of resection [2,5]. Many GISTs can be treated without major anatomical resection and therefore are suitable for minimally invasive surgery, with wedge resection of gastric GISTs widely reported to be both successful and most commonly performed [6]. With the growth in laparoscopic surgical experience subtotal and total gastrectomies are now both practical and suitable for more proximal lesions however, larger GISTs in difficult anatomical positions (oesophagus/oesophagogastric junction/proximal stomach) present a more technically demanding challenge and have a greater propensity for open surgery or intraoperative conversion. The role of laparoscopic surgery in the resection of small bowel GISTs remains unclear at present though laparoscopic excision of large bowel and rectal GISTs have been reported to be technically feasible and have successful outcomes [7,8]. The majority of reported series have supported the role of laparoscopic treatment of gastric and gastro-oesophageal GISTs, demonstrating it to be associated with lower morbidity, mortality, length of stay and rates of long term survival comparable to, if not better, than that of conventional surgery [9]. Wherever possible anatomical function should be preserved but this should not be at the cost of an R0 resection with enucleation of the tumour best avoided. In order to facilitate this a combined endoscopic laparoscopic local resection of tumours has proven to be beneficial in patients with upper GI GISTs, known as an endoscopic rendezvous procedure [10]. This technique facilitates preservation of anatomical function during the resection by ensuring lumen patency at all time. Despite initial concerns there have been favourable results reported from the resection of larger GISTs (up to 15cm in size), with no local or peritoneal recurrence after four years [11]. In order to successfully remove GISTs it is imperative to gently handle the tumour and, if at all possible, direct handling should be minimised. We have found that once the stomach has been mobilised, normally requiring the division of the gastrocolic omentum for tumours on the greater curve or the gastohepatic ligament for those on the lesser curve, placing stay sutures either side of the tumour mass greatly enhances operative control and reduces the risk of tumour cell spillage. After adequate mobilisation gastric resection is performed by elevating the stomach wall and transecting the normal stomach with a linear endoscopic GI anastomosis stapler (Figures 1 & 2, tumour arising from lesser curve). For the resection of larger lesions (>5cm),careful tactile handling and adequate traction of the tumour can be more problematic, with the use of hand assisted laparoscopic surgery (HALS) advocated by some authors [12]. While most GISTs are hard, elastic and coated with a thin pseudo-capsule some are very fragile and bleed easily. This latter group requires particular attention to ensure no tumour spillage at time of resection. Current consensus suggests that if these tumours are encountered during laparoscopic surgery, the procedure should be switched to laparoscopically assisted or conventional open surgery. As with the majority of GI neoplasms in western countries, most GIST patients present late, with complaints of vague abdominal discomfort or anaemia due to large bulky disease, and are not suitable for primary surgery at first presentation. Before 2001, surgery was the only effective treatment for GISTs however, the introduction of tyrosine kinase inhibitors as neoadjuvant chemotherapeutic agents has revolutionised the approach to these tumours with, previously irresectible lesions downstaged to the point of curative resection. This is further discussed below. Neoadjuvant treatment Combined modality strategy has shown significant benefit from imatinib mesylate (Gleevac) in downstaging GISTs, thus rendering previously inoperable tumours resectable with tumour regression of up to 80% of patients. With as many as 90% of patients developing recurrent disease during their lifetime there has been a considerable rise in our familiarity of the use of imatinib mesylate in the pre- operative setting and, for those patients that develop symptomatic or functional recurrent disease. This has been demonstrated in a variety of settings with reports of successful R0 resection in previously advanced tumours or marginally resectable tumours, including locally advanced lesions of the stomach, metastatic hepatic GISTs and in small bowel disease [13,14]. Despite an initial response to imatinib secondary or acquired resistance tends to develop after a median of two years with this most commonly due to KIT mutation in clonally expanded cells. Mutational analysis has helped to characterise the behaviour of these tumours with proximal deletions of exon 11 and duplication of exon 9 associated with high risk lesions whereas, PDGF α exon 18 mutated GISTs have a lower malignant potential. In light of this drug resistance the use of a newer agent, sunitinib malate (Sutent, SU11248), has been trialed in patients with advanced disease, with GISTs resistance to imatinib. Two phase II trials and one phase III trial have reported a significant clinical benefit with an increase in time to tumour progression and death, leading to suntinib being licensed for all patients in the US with imatinib resistant disease [15]; however tumour shrinkage compared to placebo was not common and its role as a neoadjuvant downstaging agent needs further clarification and investigation [16]. In addition, mutational analysis of the primary tumour may also help to target drug therapy, with exon 9 mutation GISTs especially sensitive to sunitnib treatment whilst at best having an intermediate response to imatinib. It is clear, at present, that a randomised clinical trial Laparoscopic resection of primary GISTs has become the the treatment of choice... with lower morbidity, mortality, length of stay and [improved] rates of longterm survival
  16. 16. 16 Volume 3 Issue 2 • August/September 2008 of these agents as neoadjuvant treatments in advanced GISTs is needed to establish any relative superiority. It is our experience that in advanced and recurrent disease, increasing the dose of imatinib mesylate (up to 800mg/day) in patients that initially have a poor response or are refractory to therapy proves to be both efficacious and therapeutic. This increase leads, in a sizeable proportion, to a decrease in tumour volume and is associated with complete surgical resection in those with locally advanced primary GISTs [17]. Early surgical intervention should be considered for imatinib responsive disease and in these patients multiple reoperation(s) are associated with prolongation of life. Conclusion The current management of GISTs continues to rapidly progress with the combination of new surgical techniques and targeted chemotherapy delivering real benefits in keeping with their promised potential expectations seen at the cellular level. The treatment of GISTs continues to evolve with dramatic reductions seen in mortality and associated surgery from this disease. n References 1. Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann Surg Oncol. 2000;7(9):705-12. 2. DeMatteo RP, Lewis JJ, Leung D, Jeung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumour: recurrence patterns and prognostic factors for survival. Ann Surg 2000 Jan;231:51-8. 3. Connolly EM, Gaffney E, Reynolds JV. Gastrointestinal stromal tumours. Br J Surg 2003;90(10):1178-86. 4. Demetri GD, Benjamin RS, Blanke CD, Blay JY et al. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST) - update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw. 2007;Jul;5 Suppl 2:S1-29. 5. Imamura M, Yamamoto H, Nakamura N, Oda Y, Yao T, Kakeji Y, Baba H, Maehara Y, Tsuneyoshi M. Prognostic significance of angiogenesis in gastrointestinal stromal tumors. Mod Pathol 2007:20(5):529-37. 6. Nowain A, Bhakta H, Pais S, Kanel G, Verma S. Gastrointestinal stromal tumours: clinical profile, pathogenesis, treatment strategies and prognosis. J Gastroenterol Hepatol. 2005;Jun;20(6):818-24. 7. Nguyen SQ, Divino CM, Wang JL, Dikman SH. Laparoscopic management of gastrointestinal stromal tumors. Surg Endosc 2006;20(5):713-6. 8. Nakamura T, Ihara A, Mitomi H, Kokuba Y, Sato T, Ozawa H, Hatade K, Onozato W, Watanabe M. Gastrointestinal stromal tumor of the rectum resected by laparoscopic surgery: report of a case. Surg Today. 2007;37(11):1004-8. 9. Novitsky YW, Kercher KW, Sing RF, Heniford BT. Long-term outcomes of laparoscopic resection of gastric gastrointestinal stromal tumors. Ann Surg 2006;Jun;243(6):738-45; discussion 745-7. 10. Ludwig K, Wilhelm L, Scharlau U, Amtsberg G, Bernhardt J. Laparoscopic- endoscopic rendezvous resection of gastric tumors. Surg Endosc. 2002 Nov;16(11):1561-5. 11. Otani Y, Kitajima M. Laparoscopic surgery for GIST: too soon to decide Gastric Cancer. 2005;8(3):135-6. 12. Yano H, Kimura Y, Iwazawa T, Takemoto H, Imasato M, Monden T, et al. Hand- assisted laparoscopic surgery for a large gastrointestinal tumor of the stomach. Gastric Cancer. 2005;8:186-92. 13. Gomez D, Al-Mukthar A, Menon KV, Toogood GJ, Lodge JP, Prasad KR. Aggressive surgical resection for the management of hepatic metastases from gastrointestinal stromal tumours: a single centre experience. HPB (Oxford). 2007;9(1):64-70. 14. Chiang KC, Chen TW, Yeh CN, Liu FY, Lee HL, Jan YY. Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate. World J Gastroenterol. 2006 Apr 7;12(13):2060-4. 15. Hopkins TG, Marples M, Stark D. Sunitinib in the management of gastrointestinal stromal tumours (GISTs). Eur J Surg Oncol. 2008 Aug;34(8):844- 50. 16. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. 17. Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW, Pollock RE, Benjamin RS, Burgess MA, Chen LL, Trent J, Patel SR, Raymond K, Feig BW. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007 Jan;14(1):14-24. 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  17. 17. Uftoral Prescribing Information (UK) Presentation: Capsules containing 100 mg tegafur and 224 mg uracil. Therapeutic Indications: First-line chemotherapy treatment of metastatic colorectal cancer in combination with calcium folinate. Dosage and administration: The dose of Uftoral is 300 mg/m2/day tegafur and 672 mg/m2/day uracil combined with 90 mg/day oral calcium folinate, given in three divided doses, at least one hour before or after meals. Calcium folinate should be taken at the same time as Uftoral. The treatment cycle is 35 days. Uftoral/calcium folinate is taken for 28 consecutive days followed by 7 days without Uftoral/calcium folinate. Only suitable for adults. Monitor patients with renal or hepatic impairment carefully. Exercise caution in patients with renal impairment. In the elderly, monitor renal, hepatic and cardiac function. Contraindications: Hypersensitivity to the constituents or 5-FU; pregnancy or breast feeding; adolescents, children and infants; severe hepatic impairment; deficiency of hepatic CYP2A6; bone marrow suppression from previous radiotherapy or antineoplastic agents; known or suspected dihydropyrimidine dehydrogenase deficiency; current or recent treatment with dihydropyrimidine dehydrogenase inhibitors such as brivudine. Special Warnings and Precautions: Patients with: renal or hepatic impairment, signs and symptoms of bowel obstruction, signs and symptoms of liver or renal disease, diarrhoea, a history of significant cardiac disease and the elderly. Monitor patients on coumarin anticoagulant treatment (such as warfarin) and phenytoin treatment. Drug Interactions: Warfarin, phenytoin, substrates or inhibitors of the CYP2A6 enzyme such as coumarin, methoxypsoralen, clotrimazole, ketoconazole, miconazole. Must not be co-administered with inhibitors of dihydropyrimidine dehydrogenase eg brivudine (allow interval of 4 weeks before Uftoral treatment). Pregnancy and Lactation: Should not be administered to patients who are pregnant or attempting to become pregnant or breast feeding. Undesirable Effects: Very common: GI disorders such as diarrhoea, nausea/vomiting, abdominal pain, asthenia, stomatitis and anorexia; blood disorders such as myelosuppression, anaemia, thrombocytopenia, leucopoenia and neutropenia; increased alkaline phosphatase, ALT, AST and total bilirubin. Common: other GI disorders including intestinal obstruction; fever, headache, malaise, chills, dehydration, cachexia; CNS disorders including taste disturbance, dizziness, depression and confusion; eye disorders, cardiac and vascular disorders including DVT; respiratory disorders; skin and musculoskeletal disorders. Uncommon: Other GI disorders, hepatitis, jaundice, liver failure, chest pain, sepsis, coagulation disorders, febrile neutropenia, arrhythmia, congestive heart failure, myocardial infarction, heart arrest, shock, pulmonary embolism, abnormal kidney function, urinary retention, haematuria, impotence. Side effects may require dose modification. Please refer to Uftoral SPC for full details of side effects. Legal Category: POM. Basic NHS cost: pack of 36 capsules - £96.12; pack of 120 capsules - £320.40. Marketing Authorisation Holder: Merck Pharmaceuticals (A Division of Merck Ltd), Harrier House, High Street, West Drayton, Middlesex, UB7 7QG, UK. MA Number: PL11648/0065. Date of Preparation: August 2007. Further information, including a summary of product characteristics is available from: Merck Serono, Bedfont Cross, Stanwell Road, Feltham, Middlesex, TW14 8NX, UK Tel: 020 8818 7373. (Uftoral is a trademark of Taiho Pharmaceutical Co., Ltd, used under license by Merck KGaA, Darmstadt, Germany) References : 1. Uftoral SmPC November 2006 Adverse reactions should be reported to Merck Serono (please see contact details within PI). Alternatively, adverse reactions may be reported using the Yellow Card Scheme (www.yellowcard.gov.uk) Date of preparation: March 2008 UFT08-0007 Uftoral: a lifestyle choice for your patients Uftoral offers people with mCRC an effective oral chemotherapy with very rare incidence of HFS.1 Allow your patients to continue with the everyday activities that are essential for their lifestyle. N ICE recom m ended Merck Serono Oncology 9904 UFT Onc News:Layout 1 20/3/08 09:29 Page 1
  18. 18. 18 Volume 3 Issue 2 • August/September 2008 F ollowing estimation of pathological staging using the criteria outlined in part 1 of this review, there are three important categories into which tumours are placed in order to determine the appropriate treatment options. These include organ confined T1 and T2 lesions, locally advanced T3 and T4 (N0 M0) tumours and metastatic disease. There are a number of treatment options available for each category and patients’ care needs to be carefully determined taking into account quality of life, competing co-morbidities, life expectancy and patient preference. The Multi-Disciplinary Team (MDT) approach to patient management is key to this process, involving surgeons, oncologists, radiologists, pathologists and specialist nursing staff. Treatment of Organ Confined Prostate Cancer Organ confined disease now represents the majority of tumours at diagnosis and is potentially curable. However, due to the long natural history of prostate cancer and the evolution of different interventions it has been difficult to effectively measure and compare the outcomes of different treatment strategies. Therefore there is a significant degree of controversy surrounding the optimum treatment of this category of disease. Again, treatment needs to be carefully planned in the MDT setting taking into account patient preference, age and co-morbidity. The three main treatment options include watchful waiting or active surveillance, radical surgery and radical radiotherapy. These options have similar long term outcomes but different side effects and complications and therefore each option should be carefully explained to the patient who can then make an informed decision. Watchful Waiting and Active surveillance Low risk, low Gleason grade disease carries only a 4-7% risk of death at 15 years and Gleason 7 disease carries a 42 – 70% risk at 15 years [1]. Thus men over the age of 75 years with organ confined disease and a life expectancy of less than 10 years are unlikely to gain benefit from radical treatment. In such cases it is generally considered appropriate to monitor disease status, termed watchful waiting, with regular PSA and DRE, offering hormone therapy if there is evidence of significant disease progression. A more proactive form of watchful waiting termed active surveillance is available for younger men with low volume, low to moderate grade disease. With more intensive follow-up using PSA, DRE and interval repeat TRUS biopsy radical treatment can be deferred until there is evidence of disease progression. Up to 50% of men are progression free at 10 years and deferred radical treatment remains effective [2]. For some men this is a viable alternative to early radical treatment and its consequent side effects. However, it should be carefully explained to patients that there is a risk that potentially treatable disease may progress during the monitoring period with an increased risk of local progression, metastatic spread and death from prostate cancer [3]. Radical Surgery Radical surgery is considered the gold standard treatment for prostate cancer in appropriately selected patients. Such patients should have a greater than 10 year life expectancy, with organ confined disease which is biologically resectable and they should be fit enough to undergo major surgery. To date there is limited data comparing surgery directly with radical radiotherapy, although surgery is considered the optimum treatment option due to the reduced risk of local recurrence. However, there is good evidence that disease progression and disease specific survival is better with surgery compared to watchful waiting [3]. There are a number of surgical approaches including open retropubic, open perineal and laparoscopic. Acute complications include haemorrhage, infection, and complications related to anaesthesia. Significant late complications include erectile dysfunction in around 50% of patients, incontinence in 10% and bladder neck stenosis in 5%. Ten year progression free survival is in the region of 85% for organ confined disease, but this falls to 55-65% with evidence of extracapsular extension, 25% with seminal vesical disease and 10% if there is nodal disease [4]. Several series of laparoscopic and robotic radical prostatectomy have recently been reported and while some reports suggest shorter recovery time, less blood loss and improved Prostate Cancer reviewed: Part 2 - Treatment Options Simon Mackie, SpR in Urology, Aberdeen Royal Infirmary, UK. Bhavan Rai, Urology Research Fellow, University of Aberdeen, UK. Correspondence to: Dept Urology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB252ZN, UK. Urological Cancer Factors Indirectly Affecting Treatment Quality of Life Co-morbidity Life expectancy Patient preference Results Pending Definitive data on optimum treatment strategy for organ confined disease is some way off. The results of a number of studies investigating the role of cancer screening are awaited

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