This document discusses anaemia in cancer patients. Some key points:
- Anaemia is very common in cancer patients, occurring in 20-60% at presentation and increasing with chemotherapy cycles.
- Anaemia can be caused by the cancer itself, chemotherapy, radiotherapy, blood loss from surgery. It adversely impacts quality of life through fatigue and other symptoms.
- More severe anaemia is associated with worse survival outcomes and prognosis. This may be due to tumour hypoxia enhancing progression.
- While red blood cell transfusions are used to treat anaemia, over a third of anaemic cancer patients receive no treatment. Recombinant erythropoietin can increase hemoglobin levels and
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
Richard S. Finn, MD, Anthony El-Khoueiry, MD, and Josep M. Llovet, MD, PhD, prepared useful practice aids pertaining to hepatocellular carcinoma for this CME activity titled "Breaking the Paradox: Expanding Options and New Questions in HCC Management: Mapping the Pathways to Better Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HU6L5K. CME credit will be available until February 14, 2020.
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
Richard S. Finn, MD, Anthony El-Khoueiry, MD, and Josep M. Llovet, MD, PhD, prepared useful practice aids pertaining to hepatocellular carcinoma for this CME activity titled "Breaking the Paradox: Expanding Options and New Questions in HCC Management: Mapping the Pathways to Better Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HU6L5K. CME credit will be available until February 14, 2020.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology. The aim of the journal is to provide a forum for cardiologists, researchers, physicians, and other health professionals to find most recent advances in the areas of cardiology and cardiovascular diseases.
Austin Journal of Clinical Cardiology accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of cardiology and circulatory system.
Austin Journal of Clinical Cardiology strongly supports the scientific upgradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: nuove possibilità di prevenzione e trattamento della tossicità acuta e tardiva
This presentation discusses the latest evidence for blood transfusion triggers in the intensive care unit of various clinical condition including severe sepsis, GI bleed, post surgical cases, and post cardiac surgery among other cnditions
Utilizing Doppler Flow to Investigate the Hemodynamic Effects of Anti-Cancer ...Scintica Instrumentation
Recent advances in targeted cancer therapies has led to the development of a number of novel approaches that have demonstrated some clinical advantages in terms of prolonging overall survival and progression free survival. One of these approaches involves inhibiting angiogenesis (the growth of blood vessels from a pre-existing vasculature), using therapies that inhibit the actions of vascular endothelial growth factor (VEGF). Although anti-VEGF therapies showed some promise in early trials and are now widely used in the treatment of a variety of diseases, including cancer, the cardiovascular side effects associated with these treatments are concerning.
The clinical community now faces the issue of using these long-term approaches to treat younger populations of patients, many of whom are now at risk of complications relating to the cardiovascular consequences of treatment, rather than the cancer itself. There is clearly a need to better understand the cardiovascular effects of anti-VEGF therapies in both acute and longer-term studies.
In this webinar, Prof Jeanette Woolard discussed the issues relating to anti-VEGF approaches, giving consideration to the signalling mechanisms by which this family of pro-angiogenic proteins evoke their effects. She contextualized this by focusing on the cardiovascular consequences of VEGF inhibition in both patient and preclinical conditions. Specifically, she reviewed the use of Doppler flowmetry models to explore the short-term cardiovascular effects of small molecule inhibitors of VEGF and expand this to longer-term consequences using implantable telemetry approaches.
Key topics covered during the webinar included:
What is the role of VEGF in normal and pathological angiogenesis?
What are the consequences of VEGF inhibition?
Why is Doppler flowmetry and unique and important model for exploring acute cardiovascular effects?
Why are chronic models important?
Where should this field of research be looking to in future?
https://www.scintica.com/webinar-utilizing-doppler-flow-to-investigate-the-hemodynamic-effects-of-anti-cancer-therapies/
Similar to Anemo 2014 - Lorusso - ESA nel paziente oncologico (20)
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
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Stay informed, stay safe, and get your flu shot today!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Anemo 2014 - Lorusso - ESA nel paziente oncologico
1. Gynecologic Oncology Unit
Domenica Lorusso
Milan - Italy
ESA NEL PAZIENTE
ONCOLOGICO
ANEMO 14
Strategie di Risparmio di Sangue
San Donato Milanese 07/03/2014
2. Prevalence of anaemia in cancer
Anaemia is the most common haematological
disorder in patients with cancer
– approximately 20%–60% of patients with
cancer will have anaemia at presentation
Treatment for cancer can induce or exacerbate
anaemia: the extent of this varies according to the
type of tumour and treatment
3. Studio ECAS:
prevalenza dell’anemia pre-terapia
Adattata da Ludwig H, et al. Eur J Cancer 2004;40:2293-306
61,7%
29,3%
1,3%
8,7%
0,0% 20,0% 40,0% 60,0% 80,0%
> 12 gr/dL
10-11.9 gr/dL
8-9,9 gr/dL
< 8 gr/dL
39.3% (5.850/ 14.912)
Hb ≤ 11.9 g/dL
6. Cancer-related anaemia in Europe:
Type of Tumor
Anaemia tended to be mild-to-moderate
(10–12 g/dL) in solid tumours
Anaemia tended to be more severe in
haematological malignancies (<10 g/dL)
There were some between-country differences in
Hb levels in different malignancies
7. The incidence of anaemia in cancer
varies according to the type of
malignancy
0
10
20
30
40
50
60
Incidenceofmoderateanaemia
(percentageofpatients)
Skillings J, et al. Eur J Cancer. 1995;31A(suppl 5):S5. Abstract.
n >30 in each group
Malignancy type
Colorectal cancer
Breast cancer
Ovarian cancer
Lung cancer
NHL
9. Studio ECAS: impatto della
chemioterapia
L’incidenza di anemia aumenta con il numero di
cicli di CT
19,5%
34,3%
42,0%
46,7% 46,7%
0,0%
5,0%
10,0%
15,0%
20,0%
25,0%
30,0%
35,0%
40,0%
45,0%
50,0%
Ciclo 1 Ciclo 2 Ciclo 3 Ciclo 4 Ciclo 5
Ludwig H, et al. Eur J Cancer 2004;40:2293-306
10. Groopman J. et al. J Natl Cancer Inst.1999;91:1616-34
Anemia (% pazienti)
Neoplasia Farmaco/combinazione
Grado
1 / 2
Grado
3 / 4
NSCLC
avanzato
Paclitaxel 23–100 5
Docetaxel 73–85 2–10
Paclitaxel/carboplatino 10–59 5–34
Paclitaxel/cisplatino 45–60 5–23
Ca Ovaio
avanzato
Carboplatino 66 0–26
Cisplatino 8 2
Paclitaxel/cisplatino 58 8
Cisplatino/ciclofosfamide 32–97 2–29
Farmaci chemioterapici e anemia
11. Cause dell’anemia nel pz neoplastico
FARMACI BIOLOGICI
Incidenza globale 22.2 %
Anemia G1-G2 31.4 %
Anemia G3-G4 6.3 %
Barni S. The Oncologist: in press
12. Causes of anaemia in patients with cancer:
Other treatment-related factors
Radiotherapy
– has direct effects on bone marrow suppression
– can impair appetite and so reduce vital nutrient
uptake
– has been shown to induce or exacerbate anaemia
in 54% of patients with solid tumours1
Anaemia may also result from blood loss due to
surgery
1Harrison L, et al. Semin Oncol. 2001;2(suppl 8):54-59.
13. Signs and symptoms of anaemia
Central nervous system
Debilitating fatigue
Dizziness, vertigo
Depression
Impaired cognitive function
Immune system
Impaired T-cell and
macrophage function
Cardiorespiratory system
Exertional dyspnoea
Tachycardia, palpitations
Cardiac enlargement,
hypertrophy
Increased pulse pressure,
systolic ejection murmur
Risk of life-threatening cardiac
failure
Gastro-intestinal system
Anorexia
Nausea
Genital tract
Menstrual problems
Loss of libido
Vascular system
Low skin temperature
Pallor of skin, mucous
membranes and conjunctivae
Adapted from Ludwig H. Semin Oncol. 1998;25(suppl 7):2-6.
15. Anaemia adversely affects
quality of life (QOL)
Fatigue is the most commonly reported clinical
manifestation of anaemia in patients with cancer
– 78% of patients with cancer suffer fatigue1
Fatigue is not relieved by sleep or rest
At Hb levels <12 g/dL, fatigue increases significantly
Hb and fatigue QOL2
1Vogelzang N, et al. Semin Hematol. 1997;34 (suppl 2):4-12.
2Cella D. Semin Hematol. 1997;34 (suppl 2):13-19.
16. Perception of cancer-related fatigue:
The prevalence of fatigue
Every day
On most days
At least once a week
Only a few
days each month
Hardly ever
Don’t know
0 5 10 15 20 25 30 35
32
21
14
11
20
2
Patients (%)
Vogelzang N, et al. Semin Hematol. 1997;34 (suppl 2):4-12.
Patients were asked how often in the past month they had felt fatigue/
did they feel fatigue while undergoing treatment
17. Crawford J, et al. Cancer. 2002;15:888-895.
70
65
60
55
50
45
40
35
30
7
Hb (g/dL)
8 9 10 11 12 13 14
Study 1 (n = 2030)
Study 2 (n = 2352)
LASAScore(mm)
Study 1: r = 0.25
Study 2: r = 0.29
P < .01
Correlation Between Hb Level and
Quality of Life
18. Anaemia is an adverse prognostic
factor in patients with cancer
Increasing evidence suggests that anaemia adversely
affects survival in patients with cancer
Anaemia and thrombocytopenia at diagnosis strongly
predicted for poor outcome in patients with chronic
lymphocytic leukaemia1
Anaemia at diagnosis was an independent adverse
prognostic factor in patients with Hodgkin’s disease2
or NHL3
1Binet J, et al. Cancer. 1981;48:198-206.
2Hasenclever D, et al. N Engl J Med. 1998;339:1506-1514.
3Moullet I, et al. Ann Oncol. 1998;9:1109-1115.
19. Anaemia as an independent prognostic
factor: Literature review
A literature review of 60 clinical studies assessed
the effects of anaemia on survival in patients with
a variety of solid tumours and haematological
malignancies1
Anaemia increased the relative risk of death by
between 19% and 75%, depending on the
malignancy
1Caro J, et al. Cancer. 2001;91:2214-2221.
20. Anaemia is associated with reduced survival in
patients with non-Hodgkin’s lymphoma
Moullet I, et al. Ann Oncol. 1998;9:1109-1115.
100
90
80
70
60
50
40
30
20
10
0
Patientsurvival(%)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years
P <0.0001
No anaemia
Anaemia
21. Anemia e sopravvivenza
I pazienti affetti da NSCLC che hanno mantenuto
livelli di Hb > a 12 gr/dL hanno avuto una maggiore
sopravvivenza
Waters JS et al., J Clin Oncol 2002;15: 601-3
22. Tumour hypoxia potentiates tumour
progression (cont’d)
Hypoxia may stimulate tumour growth by induction of
– urokinase plasminogen activator (uPA)
• leads to degradation of the tumour extracellular
matrix and subsequent metastatis1
– vascular endothelial growth factor (VEGF) secretion
• promotes angiogenesis tumour growth and
metastasis2
1Molls M. Proc 1st International Conference on Erythropoietin in Radiation
Oncology, Freiburg, Germany, June 1999.
2Dunst J, et al. Strahlenther Onkol. 1999;175:93-96.
23. Tumour hypoxia potentiates tumour
progression
The impact of anaemia on the survival of patients with
cancer may be due to low tumour levels of oxygen
Experimental data show that tumour hypoxia leads to
– tumour invasiveness
– metastatic potential
– resistance to cancer therapy1
Hypoxia may also promote the selection of aggressive
tumour phenotypes with reduced apoptotic potential
1Höckel M, et al. Cancer Res. 1999;59:4525-4528.
24. Anemia e sopravvivenza
Il decremento della Hb durante il trattamento
CT/RT per NSCLC stadio III si correla in modo
significativo alla sopravvivenza
MacRae R. et al; Radiother Oncol. 2002;64(1):37-40
25. Increasing serum Hb levels may improve
survival in patients with cancer receiving
CHT
In a placebo-controlled trial of 375 anaemic patients receiving non-
platinum–based chemotherapy for a variety of malignancies,
administration of recombinant EPO (rHuEPO) led to a:
– significant increase in Hb levels (P <0.001)
– significant decrease in transfusion requirements (P = 0.0057)
– significant improvement in QOL (P <0.01)
– trend towards an increase in survival (12-month estimated rates:
60% vs 49% for placebo)*
Littlewood T, et al. J Clin Oncol. 2001;11:2865-2874.
*NB: This study was not powered for
survival as an endpoint
26. Perception of cancer-related fatigue: Different perceptions of the
importance of treating fatigue
0 20 40 60 80 100
Oncologists
Patients
Response (%)
Fatigue
Pain
Both equally
Oncologists and patients were asked if it is/was more important for
pain or fatigue to be reduced or relieved by treatment or are/were
both equally important
41
5
34
94
6
1
Vogelzang N, et al. Semin Hematol. 1997;34 (suppl 2):4-12.
27. Perception of cancer-related fatigue:
Different perceptions of the main cause of fatigue
0 10 20 30 40 50 60 70
Caregivers
Oncologists
Patients
Response (%)
Illness
Treatment
Both
13
54
14
54
41
64
13
3
14
Vogelzang N, et al. Semin Hematol. 1997;34 (suppl 2):4-12.
28. ECAS – Trattamento dell’anemia
Pazienti in chemioterapia - Hb nadir < 11 g/dl (n = 4.622)1
1. Ludwig H, et al. Eur J Cancer 2004;40:2293-2306
* Inclusi pazienti che ricevevano solo ESP, ESP + trasfusione, ESP + trasfusione + ferro;
** Inclusi pazienti che ricevevano solo trasfusione e trasfusione + ferro
29. Studio ECAS: trattamento
Il 61.1% dei pazienti
NON riceve nessun
trattamento per
l’anemia !!!
Ludwig H, et al. Eur J Cancer 2004;40:2293-306
30. UK audit of RBC transfusions and anaemia
in patients with cancer (cont’d)
Approximately one-third of patients required a RBC
transfusion
The following factors were significantly associated
with a higher incidence of RBC transfusion
– pretreatment Hb <11 g/dL vs no anaemia
– lung/ovarian vs breast/testicular tumours
– metastatic vs non-metastatic disease
(for breast testicular and ovarian cancers)
Barrett-Lee P, et al. Br J Cancer. 2000;82:93-97.
31. UK audit of RBC transfusions and
anaemia in patients with cancer
(cont’d)
Barrett-Lee P, et al. Br J Cancer. 2000;82:93-97.
Proportion of patients requiring RBC transfusion (n)
Tumour Any transfusion >1 transfusion
All 33% (902) 16% (443)
Lung 43% (335) 22% (170)
Ovary 41% (347) 21% (179)
Testes 24% (51) 14% (29)
Breast 19% (169) 7% (65)
32. RBC transfusions
Until recently RBC transfusion was the therapy of choice for
symptomatic anaemia
RBC transfusion is still appropriate for patients requiring
– rapid correction of Hb, eg, chronic symptomatic anaemia
– an increase in blood volume, eg, severe haemorrhage
However
The effects of RBC transfusion are short-lived
RBC transfusion does not address the underlying process of anaemia
34. L’obiettivo della terapia con EPO
INCREMENTARE
I LIVELLI DI Hb
RIDURRE LA
NECESSITA’ DI
TRASFUSIONI
MIGLIORARE LA
QUALITA’ di VITA
35. Erythropoietin for anemia in cancer patients
413 patients, Hb< 10.5 gr/dl
no CT vs CT w CDDP vs CT w/o CDDP
(epoetin 150 U/kg 3 times weekly for 12 weeks)
FDA APPROVAL
(1993)
36. • Treatment with ESA
– reduces transfusion requirement
– improves hematopoietic response
– provide clinically meaningful improvements in overall health
in patients receiving chemotherapy
Recombinant Human Erythropoietins and
Cancer Patients: Update Meta-Analysis of 57
Studies including 9353 Patients
Bohlius J. Et al. J Natl Cancer Inst. 2006
39. 53 studi clinici randomizzati
N=13.933
Mortalità in studio
HR = 1.17 [95% CI, 1.06-1.30] p=0.003
Overall Survival
HR = 1.06 [95% CI, 1.00-1.12] p=0.0046
Nei pazienti anemici il trattamento con ESA
aumenta in modo statisticamente
significativo la mortalità e diminuisce la
sopravvivenza
Bohlius, Lancet 2009
Tutti i pazienti trattati con ESA
(popolazione globale anche fuori indicazione)
40. Alcuni studi hanno rilevato una tendenza verso una maggiore
sopravvivenza nel gruppo che riceveva ESA rispetto al gruppo placebo
(obiettivo secondario).
Si è quindi sviluppato un filone di ricerca indirizzato alla valutazione di
un possibile beneficio del trattamento con ESA in termini di
sopravvivenza
Razionale:
• la condizione anemica può peggiorare la prognosi del paziente
oncologico (ipo-ossigenazione tissutale ridurrebbe l’efficacia CHT/RT)
Farmaci che riescono a incrementare i livelli di Hb potrebbero avere
un effetto benefico anche sui i livelli di ossigenazione tessutale,
aumentando quindi la risposta alla CHT/RT.
41. Studi sperimentali fuori indicazione
Riunione AM – 14 marzo 2007
Target Hb elevato
PFS differenze n.s.
Studio Blohmer evidenzia trend positivo
Thomas 2008
GOG191
Epo Alfa
Fuori indicazione (solo RT, Hb basale e target elevato)
Beyond anemia
Non valuta attività di EpoR ma solo presenza
Usa un metodo non specifico (Ab anti epoR C20, riconoscono
altra proteina: HSP70)
I recettori sono espressi (mRNA) ma non trasportati in superficie
(epo marcata non si lega)
Henke
2003
Henke (EpoR)
2006
Epo Beta
(solo polmone)
Sospeso l’arruolamento, non il trattamento (CERA x12 weeks)
Non pubblicatoCERA
Pazienti molto avanzati
Pazienti non in trattamento o trattamento non curativo
Wright
2007
Epo Alfa
Fuori indicazione (Hb basale e target elevato, 1 anno tratt.)
Beyond anemia (aumento TVE fatali)
Stesso Time to Progression nei due bracci
Leyland Johnes
2003
Epo Alfa
Key PointsStudioMolecola
Reactive Key Points
Molecola Studio Key Points
Nesp PREPARE
Non pubblicato
Prevenzione dell’anemia
Risposta patologica uguale tra i gruppi: no effetto epo su cht
Studio di Mobusnon mostra differenze tra i due gruppi
Nesp DAHANCA
Abs, Eur J Cancer
Solo Rt
Non anemici
Nesp Smith 2008 No cht; no RT
500 Q4W
Nesp Hedenus2003 Target elevato
42. Gli studi negativi sono fuori indicazione
Si tratta di 8 studi condotti in ambito sperimentale e al di
fuori delle indicazioni per una o più delle seguenti ragioni:
• Pazienti non anemici (elevati livelli di Hb basale ed elevato
target)
Pazienti non in chemioterapia
Inoltre:
Non tutti hanno l’outcome come obiettivo primario
Molti sono stati interrotti e i risultati non possono essere
conclusivi
43. Valore HB ESA (n=7634) Control (n=6229)
<8 448 (6%) 343 (5%)
8<10 2222 (29%) 1708 (27%)
10<12 2851 (37%) 2153 (34%)
>12<14 1433 (22%) 1410 (22%)
>14 428 (6%) 411 (7%)
missing 252 (3%) 274 (4%)
53 Studi considerati
44. • Solo CT in 34 studi (64%)
• NO CT in 15 studi (27%)
• NO CT e NO RT in 4 studi (9%)
53 Studi considerati
45. 38 studi clinici randomizzati
N=10.441
Mortalità in studio
HR = 1.10 [95% CI, 0.98-1.24] p=0.12
Overall Survival
HR = 1.04 [95% CI, 0.97-1.11] p=0.263
Nei pazienti anemici in CHT non esiste
differenza statisticamente significativa tra
il gruppo dei pt trattati e quello controllo
in termini di mortalità e sopravvivenza
Bohlius, Lancet 2009
Solo pt con anemia indotta da CHT
46. Autore Pt Tipo tumore Arms Commenti
Pronzato,
The Oncologist 2010
N=223 • Cancro alla mammella
(~50% in stadio avanzato)
• Anemia lieve (Hb ≤12.0
g/dL)
Epo alfa
vs
BSC
• Nessuna differenza statisticamente significativa nella
sopravvivenza
HR= 1,05 (CI 95% 0,58-1,92) p=0.86
Aapro,
JCO 2008
N=463 • Cancro alla mammella
metastatico
• Hb< 12,9 g/dl
Epo beta
vs
control
• Nessuna differenza statisticamente significativa:
- Sopravvivenza globale
HR=1.07 (95% CI, 0.87 -1.33) p =0.522
- Sopravvivenza libera da progressione malattia
HR=1.07 (95% CI, 0.89-1.30) p=0.488
Cantrell,
Cancer 2010
N=343 • Cancro all’ovaio ESA
vs
No ESA
• Analisi retrospettiva
• Le pazienti trattate con ESA avevano fattori prognostici
sfavorevoli (più anziani, stadio più avanzato di malattia, più
ipertese)
• Nessuna differenza statisticamente significativa:
- Sopravvivenza globale
OR=0.851 p=0.35
- Sopravvivenza libera da progressione malattia
OR=0.959 p=0.488
Blohmer,
JCO 2011
N=257 • Carcinoma cervicale in stadio
non avanzato
• Target Hb: 12,5-13.5 g/dl
ESA
vs
No ESA
• Nessuna differenza statisticamente significativa nella
sopravvivenza globale
HR: 0.88 [95% CI, 0.51-1.50], p=0,63
Stehman F,
Gynecologic Oncology
2012
N=1864 • Cancro ovarico epiteliale, alle
tube di falloppio o primario
peritoneale dopo chirurgia
• Stadio avanzato
ESA
vs
No ESA
• Nessuna differenza statisticamente significativa:
- Sopravvivenza globale
HR=0,989 [IC95% 0,849–1,15] p=0.892
- Sopravvivenza libera da progressione malattia
HR=1,06 [IC 95% 0,937–1,19] p=0.364
Studi positivi
47. Autore Pt Tipo tumore Arms Commenti
Milroy,
European Journal
of Clinical &
Medical Oncology
2011
N=424 • Cancro al polmone non a
piccole cellule, stadio avanzato
metastatico
• Pazienti non anemici (14-15
g/dl)
Epo alfa
vs
BSC
• I pazienti sono mantenuti a dei livelli di Hb superiori a 12 g/dl
• Nessuna differenza statisticamente significativa nella
sopravvivenza globale
Hoskin,
JCO 2012
N=223 • Tumore Testa-Collo
• No anemia (Hb ≤15.0 g/dL)
RT+Epo
alfa
vs
RT
• Nessuna differenza statisticamente significativa nella
sopravvivenza
p=0.83
Engert ,
JCO 2010
N=1379 • Linfoma di Hodking
(stadio IIB-IV)
Epo alfa
vs
placebo
• Nessuna differenza statisticamente significativa nella
sopravvivenza
HR= 0,74 (95% CI 0,45-1,22)
Richardson ,
JCO 2010
N=677 • Mieloma Multiplo • Nessuna differenza statisticamente significativa nella
sopravvivenza
HR 0.945 (CI 95% 0.714-1.250) p=0.6907
Studi positivi
58. • Maggiore incidenza di eventi tromboembolici
– 7% vs 4%
• Mortalità per eventi tromboembolici simile
– 1% vs 1%
Aapro M. British Journal of Cancer (2008) 99, 14 – 22