This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
The dream of any physician and consequently every patient is to receive the right treatment in the right time with cost effectiveness. To achieve this goal, the 3 pillars: evidence based medicine, clinical research innovation & resources utilization should be integrated efficiently.
In this presentation, I'll try to comprehensively review the following:
1- How are we used to perform clinical trials in Oncology?
2- Does it fits in today’s needs?
3- Integration of biology knowledge in shaping drug development
4- New Clinical trial designs “Can they offer solution for accelerating drug development?”
5- The supporting infrastructure role in clinical trial execution
Gemcitabine and Cisplatin In Metastatic Carcinoma Gallbladder. A Single Insti...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
The dream of any physician and consequently every patient is to receive the right treatment in the right time with cost effectiveness. To achieve this goal, the 3 pillars: evidence based medicine, clinical research innovation & resources utilization should be integrated efficiently.
In this presentation, I'll try to comprehensively review the following:
1- How are we used to perform clinical trials in Oncology?
2- Does it fits in today’s needs?
3- Integration of biology knowledge in shaping drug development
4- New Clinical trial designs “Can they offer solution for accelerating drug development?”
5- The supporting infrastructure role in clinical trial execution
Gemcitabine and Cisplatin In Metastatic Carcinoma Gallbladder. A Single Insti...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
astragalus injection as an adjuvant treatment for colorectal cancer: a meta-a...LucyPi1
Abstract
Background: The combination of Chinese patent medicine Astragalus injection and Western medicine has
achieved a certain clinical effect in colorectal cancer patients. However, due to the uneven basic conditions and
research indicators of these clinical trials, it is difficult to comprehensively evaluate the effect of Astragalus
injection in the adjuvant treatment of colorectal cancer. This study aimed to systematically evaluate the efficacy
and safety of Astragalus injection as an adjuvant treatment for colorectal cancer. Methods: The Cochrane Library,
VIP database, Wanfang database, and Chinese Academic Journal Full Text database were searched for potentially
eligible articles from inception to December 15, 2018. Randomized controlled trials in which patients were
diagnosed with colorectal cancer were included. Patients in the control group received chemotherapy alone or
combined with other drugs, or chemotherapy combined with radiotherapy. Patients in the experimental group were
treated with Astragalus injection combined with interventions in the control group. Results: A total of 8 articles
were included. Compared with Western medicine alone, the Astragalus injection could improve the therapeutic
effect (RR = 1.18, 95% CI (1.01, 1.38), P = 0.03), improved the quality of life of colorectal cancer patients (SMD =
1.18, 95% CI (0.86, 1.50), P <0.001), inhibited leukopenia (RR = 0.55, 95% CI (0.42, 0.71), P < 0.001), reduced
neurotoxicity (RR = 0.43, 95% CI (0.34, 0.56), P < 0.001), and reduced the incidence of nausea and vomiting (RR
= 0.67, 95% CI (0.55, 0.80), P < 0.001). Conclusion: Astragalus injection can reduce the toxicity and improve the
efficiency of the conventional Western medicine in the treatment of colorectal cancer.
Overall patient satisfaction was significantly higher in homeopathic than in ...home
The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in
relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS
due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias
in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted
UPDATED-Early Phase Drug Developmetn and Population PK and Its' ValueE. Dennis Bashaw
Presentation Given at Regional AAPS DDDI Meeting in Baltimore. Similar to previous talks BUT updated to include a discussion of BIA 10-2474 and extended discussion of risk
Inappropriate drug use in hospitalized elderly patients of medicine and cardi...Apollo Hospitals
National committee on quality assurance, USA convened an expert consensus panel and identified the list of drugs which should be avoided in the elderly people. This resulting list of drugs after 2003 beers criteria were added to the 2006 Health Plan Employer Data and Information Set (HEDIS) to assess the drug prescribing in elderly people.
astragalus injection as an adjuvant treatment for colorectal cancer: a meta-a...LucyPi1
Abstract
Background: The combination of Chinese patent medicine Astragalus injection and Western medicine has
achieved a certain clinical effect in colorectal cancer patients. However, due to the uneven basic conditions and
research indicators of these clinical trials, it is difficult to comprehensively evaluate the effect of Astragalus
injection in the adjuvant treatment of colorectal cancer. This study aimed to systematically evaluate the efficacy
and safety of Astragalus injection as an adjuvant treatment for colorectal cancer. Methods: The Cochrane Library,
VIP database, Wanfang database, and Chinese Academic Journal Full Text database were searched for potentially
eligible articles from inception to December 15, 2018. Randomized controlled trials in which patients were
diagnosed with colorectal cancer were included. Patients in the control group received chemotherapy alone or
combined with other drugs, or chemotherapy combined with radiotherapy. Patients in the experimental group were
treated with Astragalus injection combined with interventions in the control group. Results: A total of 8 articles
were included. Compared with Western medicine alone, the Astragalus injection could improve the therapeutic
effect (RR = 1.18, 95% CI (1.01, 1.38), P = 0.03), improved the quality of life of colorectal cancer patients (SMD =
1.18, 95% CI (0.86, 1.50), P <0.001), inhibited leukopenia (RR = 0.55, 95% CI (0.42, 0.71), P < 0.001), reduced
neurotoxicity (RR = 0.43, 95% CI (0.34, 0.56), P < 0.001), and reduced the incidence of nausea and vomiting (RR
= 0.67, 95% CI (0.55, 0.80), P < 0.001). Conclusion: Astragalus injection can reduce the toxicity and improve the
efficiency of the conventional Western medicine in the treatment of colorectal cancer.
Overall patient satisfaction was significantly higher in homeopathic than in ...home
The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in
relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS
due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias
in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted
UPDATED-Early Phase Drug Developmetn and Population PK and Its' ValueE. Dennis Bashaw
Presentation Given at Regional AAPS DDDI Meeting in Baltimore. Similar to previous talks BUT updated to include a discussion of BIA 10-2474 and extended discussion of risk
Inappropriate drug use in hospitalized elderly patients of medicine and cardi...Apollo Hospitals
National committee on quality assurance, USA convened an expert consensus panel and identified the list of drugs which should be avoided in the elderly people. This resulting list of drugs after 2003 beers criteria were added to the 2006 Health Plan Employer Data and Information Set (HEDIS) to assess the drug prescribing in elderly people.
Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: effica...Enrique Moreno Gonzalez
Recombinant human endostatin (rh-endostatin) is a novel antiangiogenesis drug developed in
China. Previous experiments have shown that rh-endostatin can inhibit the proliferation and
migration of endothelial cells and some types of tumor cells. In this study, we evaluated the
efficacy and safety profiles of combination therapy of rh-endostatin and neoadjuvant
chemotherapy for breast cancer patients in a prospective, randomized, controlled, phase II
trial.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Secondary Malignancy after Treatment of Prostate Cancer. Radical Prostatectom...asclepiuspdfs
Background: This study aims to determine whether the treatment of locally confined prostate cancer (PCa) with external radiotherapy (EBRT) increases the risk to develop secondary malignancies (SM) compared to radical prostatectomy (RPE). Materials and Methods: Data from patients who were treated curatively with RPE or EBRT from 2010 to 2018 and who did not have distant metastases, previous malignancy, or previous treatment with radiotherapy or chemotherapy at the time of diagnosis were reviewed to determine the incidence of SM over a median follow-up period of 47 months (range 12–96 months). Regression models were used to correlate the clinicopathological factors with the incidence of SM.
Presented at the American Society for Clinical Oncology Gastroenterology in January 2017 in San Francisco by Eric Raymond
Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings.
Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing.
Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%).
Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...daranisaha
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...eshaasini
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...semualkaira
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...semualkaira
: Prolyl 4-hydroxylase, beta polypeptide (P4HB)
and Glucose‑regulated protein 78 (GRP78) represent for poor
prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer
The Impact of Lymph Node Dissection on Survival in Intermediate- and High-Ris...semualkaira
Aimed to evaluate the therapeutic effect of pelvic lymph node dissection (PLND) on survival and determine the predictors of lymph node involvement (LNI) in patients with intermediate- or high-risk prostate cancer (PCa) treated with Radical Prostatectomy
The Impact of Lymph Node Dissection on Survival in Intermediate- and High-Ris...semualkaira
Aimed to evaluate the therapeutic effect of pelvic lymph node dissection (PLND) on survival and determine the
predictors of lymph node involvement (LNI) in patients with intermediate- or high-risk prostate cancer (PCa) treated with Radical
Prostatectomy
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
1. Chin Med J 2013;126 (17)
3348
Meta analysis
Chemotherapy with or without gefitinib in patients with advanced
non-small-cell lung cancer: a meta-analysis of 6844 patients
ZHOU Hang, ZENG Chao, WANG Li-yang, XIE Hua, ZHOU Jin, DIAO Peng, YAO Wen-xiu, ZHAO Xin and WEI Yang
Keywords: non-small-cell-lung cancer; gefitinib; meta-analysis
Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC), in whom
chemotherapy had failed. Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival
(OS) and progression free survival (PFS). This study was to evaluate the effects of chemotherapy plus gefitinib versus
chemotherapy alone on survival of patients with NSCLC.
Methods We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference
lists of articles, and proceedings of major meetings for relevant literature. Randomized controlled trials (RCTs) comparing
chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis.
The primary endpoints were OS and PFS.
Results Of 182 relevant studies, 12 were included in the final analysis, which consisted of 6844 patients with NSCLC.
Overall, we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefitinib-free therapy, but
this difference was not statistically significant (HR, 0.92; 95% CI: 0.85–1.00; P=0.051). Furthermore, gefitinib therapy had
significantly longer PFS compared to gefitinib-free therapy (HR, 0.72; 95% CI 0.60–0.87, P=0.001). Patients receiving
gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR, 2.51; 95% CI, 1.67–
3.78, P <0.001). Rashes, diarrhea, dry skin, pruritus, paronychia, and abnormal hepatic function were more frequent in the
gefitinib therapy group.
Conclusions Treatment with gefitinib had a clear effect on PFS and ORR, and it might contribute considerably to the OS.
Furthermore, there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.
Chin Med J 2013;126 (17): 3348-3355
N
on-small-cell lung cancer (NSCLC) accounts
for approximately 80%–85% of all cases of lung
cancer, and is the most common cause of cancer death in
industrialized countries.1,2 In patients with locally advanced
and metastatic NSCLC short-lived responses to aggressive
chemotherapy are observed in approximately 30% of the
patients; the impact on the patients’ survival has been
modest.1,3
The treatment armamentarium for advanced NSCLC has
expanded to include molecular targeted therapies that act
specifically against key components of cellular pathways
involved in tumor growth, progression, and cell death.4,5
Gefitinib is an orally administered tyrosine kinase inhibitor
of the epidermal growth factor receptor (EGFR), which has
already clinically validated therapeutic targets in NSCLC.
It inhibits growth and causes regressions in the human
tumor xenografts with EGFR overexpression. Furthermore,
unlike conventional chemotherapy, gefitinib did not cause
myelosuppression, neuropathy, or significant alopecia.5-7
Despite all of these improvements, the benefits associated
with gefitinib are modest and serve to stress the need for
novel therapeutic approaches. In addition, several largescale randomized controlled trials investigating the use
of gefitinib therapy have been performed. Some studies
illustrated that gefitinib therapy had beneficial effects
on the OS or PFS when compared to the traditional
chemotherapy,8-13 while others showed little effect and
some trials even found that gefitinib therapy could induce
some harmful effects.14-19 To better understand the effect of
gefitinib therapy on OS and PFS in patients with NSCLC,
data from these recent trials need to be evaluated to
formulate a conclusion regarding the efficacy of gefitinib
therapy. We therefore undertook a meta-analysis to update
the results and resolve the uncertain efficacy of gefitinib in
patients with NSCLC. Furthermore, we also reported the
efficacy of gefitinib treatment in some specific subgroups.
METHODS
Publication search
For inclusion in our research, randomized controlled
trials of gefitinib therapy in English literature were
eligible for inclusion in our meta-analysis, regardless
of the publication status (published, unpublished, in
press, and in progress). Relevant trials were identified
by the following procedure: (1) Electronic searches: we
DOI: 10.3760/cma.j.issn.0366-6999.20122920
Department of Chemotherapy, Sichuan Cancer Hospital, Chengdu,
Sichuan 610041, China (Zhou H, Wang LY, Xie H, Zhou J, Diao P,
Yao WX, Zhao X and Wei Y)
Department of Gastroenterology, Third People’s Hospital of
Chengdu, Chengdu, Sichuan 610031, China (Zeng C)
Correspondence to: Dr. YAO Wen-xiu, Department of Chemotherapy,
Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China (Tel &
Fax: 86-28-85420847. Email: yaowenxiu_2011@126.com)
2. Chinese Medical Journal 2013;126 (17)
searched the electronic databases Medline, EmBase, and
the Cochrane Central Register of Controlled Trials for
articles up to 20 January 2012, using “gefitinib”, “clinical
trial” and “randomized controlled trial” as the search
terms. All reference lists from reports on non-randomized
controlled trials were searched manually for additional
eligible studies; (2) Other sources: we contacted authors
to obtain any possible additional published or unpublished
data, and searched the proceedings of annual meetings in
the Cochrane Cardiovascular Disease Group Specialized
Register. The relevant reviews and meta-analyses regarding
the role of gefitinib therapy for NSCLC patients were
examined for potential inclusive trials. In addition, we
searched for ongoing randomized controlled trials, which
had been registered as completed but not yet published,
in the metaRegister of Controlled Trials. Medical subject
headings and methods, patient population, and intervention
were used to identify the relevant trials.
Inclusion criteria
The literature search was undertaken independently by
three authors (Zhou H, Zeng C, and Wang LY) with a
standardized approach, and any disagreement between
these three authors was settled by a fourth author (Yao WX)
until a consensus was reached. All completed randomized
controlled trials assessing the effects of gefitinib therapy
compared to the effects of a non-gefitinib therapy, and
reporting at least one of the primary outcomes were
included as eligible trials.
Data extraction and quality assessment
Two investigators (Xie H and Zhou J) independently
extracted and collected data using a standardized dataextraction protocol. Disagreements were adjudicated by
a third reviewer (Wei Y) after referring to the original
articles.
The data collected included baseline patient characteristics
(number of patients, age, sex, pre-existing diseases,
interventions, disease status, treatment status, and duration
of follow-up), publication details, and methodological
components. The outcomes investigated included overall
survival (OS), progression free survival (PFS), objective
tumor response rate (ORR), and possible drug-correlated
adverse reactions. The quantitative 5-point Jadad score20
was used to assess the quality of the inclusive trials based
on randomization, concealment of treatment allocation,
blinding, completeness of follow-up, and use of intentionto-treat analysis (Diao P and Zhao X).
Statistical analysis
The primary efficacy outcomes of our meta-analysis
were OS and PFS. The log hazard ratios (HRs) and their
variances were estimated using the methods proposed
by Parmar21 and confidence intervals (CIs) of HRs were
reported. The summary of HRs and their 95% CIs were
estimated using a general variance-based method. For ORR
and possible drug-correlated adverse reactions, the pooled
estimation plotted as odd ratios (ORs) were obtained. The
3349
subgroup analyses were prospectively planned according
to number of patients, median age, gender, control drug,
treatment status, follow-up, smoker, racial, disease status,
pre-existent disease, EGFR FISH, and Jadad score.
Heterogeneity between trials was evaluated by the Chisquare test and I-squared statistic. These indices assess
the percentage of variability across studies attributable to
heterogeneity rather than chance. Statistical heterogeneity
was considered significant when P <0.10.22 Although the
fixed-effects model and random-effects model yielded
similar conclusions, we chose to use the random-effects
model, which assumed that the true underlying effect
varied among included trials. Moreover, many investigators
consider the random-effects model to be a more natural
choice than the fixed effects model in medical decisionmaking contexts.23,24 The probability of publication bias
was assessed with the funnel plots and the Egger test.25 All
reported P values were two-sided and P values less than
0.05 were regarded as statistically significant. Statistical
analyses were carried out using STATA 10.0 (StataCorp,
USA).
RESULTS
Search of the published literature
We identified 182 potentially relevant trials from our
initial electronic search, and excluded 136 trials after a
preliminary review. The remaining 46 studies were assessed
in detail and 12 randomized controlled trials met the
inclusion criteria (Figure 1), which included 6844 patients
with NSCLC. All the included trials were published in full
text. Table 1 summarized the baseline characteristics of the
participants and the design of the studies included.
Characteristics of the included studies
The trials included in this study compared gefitinib therapy
with the non-gefitinib control. The follow-up for patients
ranged from 7.2 to 60.0 months, with a mean of 33 months.
The population of the trials ranged from 161–1692 patients,
with a mean of 570. Jadad scale was used to assess the
quality of the included trials. Seven trials had a score of 4,
Figure 1. Diagram of the literature search and trial selection
process.
3. Chin Med J 2013;126 (17)
3350
Table 1. Baseline characteristics for included trials
Trials
ISEL (2005)14
INVITE (2008)15
V-15-32 (2008)16
SWOG S0023 (2008)17
INTEREST (2008)18
INSTEP (2009)19
IPASS (2009)8
Number of Median age Sex, male Stage IIIB
Patients
(years)
(%)
or IV (%)
1692
62
67
81
196
74
76
100
489
20 years or older
62
83
243
61
63
52
1466
61
65
79
201
75
61
NG
1217
57
21
100
ISTANA (2010)9
WJTOG 3405 (2010)10
161
172
57
64
61
31
100
59
North-East Japan (2010)11
230
63
36
91
WJTOG 0203 (2010)12
604
62
64
100
EORTC 08021/ILCP
01/03 (2011)13
173
62
77
100
and the remaining five trials had a score of 3.
Overall survival
Data for OS were available from 11 trials, which consisted
of 6614 patients with NSCLC. We noted that gefitinib
therapy had an 8% improvement in the OS as compared
to the gefitinib-free treatment arm (HR, 0.92; 95% CI:
0.85–1.00; P=0.051; Figure 2) under a random-effect
model, but was not associated with a statistically significant
Second line
First line
First line
Second line
Second line
Second line
First line
Follow-up
(months)
7.2
20
36
60
7.6
24
24
OS, ORR
OS, PFS, ORR
OS, PFS, ORR
OS, PFS
OS, PFS, ORR
OS, PFS, ORR
OS, PFS, ORR
4
3
3
3
4
4
4
Second line
Second line
15
40
OS, PFS, ORR
OS, PFS, ORR
3
3
First line
42
PFS, ORR
4
First line
60
OS, PFS, ORR
4
Second line
60
OS, PFS, ORR
4
Intervention
Treatment status
Gefitinib; placebo
Gefitinib; vinorelbine
Gefitinib; docetaxel
Gefitinib; placebo
Gefitinib; docetaxel
Gefitinib; placebo
Gefitinib;
carboplatin plus paclitaxel
Gefitinib; docetaxel
Gefitinib; cisplatin plus
docetaxel
Gefitinib; paclitaxel and
carboplatin
Gefitinib; platinumdoublet chemotherapy
Gefitinib; placebo
Main endpoint Jadad score
improvement in the OS. In addition, heterogeneity was
observed in the magnitude of the effect across the trials
included. According to a sensitivity analysis, we excluded
the V-15-32 study.16 This trial specifically included patients
were more younger, and the proportion of IIIB or IV
was less than other trials. After this, we could conclude
that gefitinib therapy yielded a clinically and statistically
significant 9% improvement in OS compared with gefitinibfree therapy (HR, 0.91; 95% CI: 0.84–0.98; P=0.015;
Table 2. Summary of the odds ratios of all toxicities outcomes assessed
Outcomes
Rash
Diarrhoea
Nausea
Anorexia
Vomiting
Dry skin
Constipation
Pruritus
Pyrexia
Asthenic condition
Cough
Dyspnea
Stomatitis
Hemoptysis
Pneumonia
Cancer pain
Edema peripheral
Paronychia
Fatigue
Anemia
Hypokalemia
Neutropenia
Leukopenia
Febrile neutropenia
Upper abdominal pain
Abnormal hepatic function
Insomnia
Alopecia
Myalgia
Neurotoxicity
Arthralgia
Dyspepsia
Dizziness
Sensory disturbance
Thrombocytopenia
Included studies
8–16,18,19
8–16,18,19
8–10,12,14–16,18,19
8,9,11,12,14–16,18,19
8,9,11,12,14–16,18,19
8,9,11,12,14–16,18,19
8–10,12,14–16,18,19
8,9,14,16,19
14–16,18
8,9,14,15,18
9,13,14,18
9,10,13–15,18,19
8–10,12,14,16,18,
9,14
11–14,18,19
9,13,14
14–16,18,19
8–10,14,16
10–13,15,16,19
10–13,15,18,19
13,15
10–13,15,16,18
10,12,15,16
8,12,15,16,18
9,15,19
13,16
9,16,19
8–10,16,18
8,9,16,18
8,9,13,16
8,9,13
9,11,13
9,13
10–12
10–13
OR and 95% CI
8.73 (6.13, 12.45)
2.63 (1.96, 3.52)
0.47 (0.28, 0.79)
0.70 (0.47, 1.06)
0.88 (0.54, 1.45)
10.37 (5.98, 18.01)
0.56 (0.40, 0.78)
3.03 (1.67, 5.49)
0.79 (0.41, 1.53)
0.45 (0.25, 0.80)
0.94 (0.76, 1.17)
0.96 (0.79, 1.17)
1.24 (0.77, 2.00)
1.34 (0.86, 2.11)
0.97 (0.70, 1.34)
0.69 (0.37, 1.28)
0.47 (0.33, 0.68)
14.00 (1.14, 171.75)
0.35 (0.19, 0.63)
0.29 (0.14, 0.61)
0.34 (0.09, 1.34)
0.05 (0.01, 0.28)
0.08 (0.01, 0.69)
0.19 (0.05, 0.70)
0.61 (0.20, 1.82)
5.76 (3.15, 10.55)
1.36 (0.60, 3.10)
0.06 (0.05, 0.09)
0.18 (0.14, 0.24)
0.19 (0.05, 0.65)
0.15 (0.04, 0.55)
0.45 (0.05, 3.89)
1.09 (0.40, 2.93)
0.13 (0.02, 0.77)
0.37 (0.20, 0.71)
P values
<0.001
<0.001
0.004
0.09
0.62
<0.001
<0.001
<0.001
0.48
0.006
0.59
0.68
0.38
0.20
0.85
0.24
<0.001
0.04
<0.001
0.001
0.12
<0.001
0.02
0.01
0.37
<0.001
0.46
<0.001
<0.001
0.008
0.004
0.47
0.87
0.02
0.003
Heterogeneity (%)
77
73
93
87
87
64
76
79
85
91
0
0
79
0
13
31
38
87
78
84
0
98
97
88
53
0
66
38
4
95
83
88
0
86
51
P values for heterogeneity
<0.001
<0.001
<0.001
<0.001
<0.001
0.004
<0.001
<0.001
<0.001
<0.001
0.61
0.79
<0.001
0.37
0.33
0.23
0.17
<0.001
<0.001
<0.001
0.38
<0.001
<0.001
<0.001
0.12
0.68
0.05
0.17
0.37
<0.001
0.003
<0.001
0.45
<0.001
0.11
4. Chinese Medical Journal 2013;126 (17)
3351
Overall, we noted that gefitinib
therapy yielded a clinically and
statistically significant 28%
improvement in PFS as compared
to the traditional chemotherapy
without gefitinib (HR, 0.72; 95%
CI 0.60–0.87, P=0.001, Figure
3). Although there was some
evidence of heterogeneity across
the studies included, however,
after sequential exclusion of each
trial from all pooled analysis, the
results were not affected by the
exclusion of any specific trial.
Overall response rate
Data for ORR was available
from 11 trials including 6601
patients. Overall, we noted that
gefitinib therapy increased the
objective response rate by 151%
when compared to gefitinibfree therapy (OR, 2.51; 95% CI:
1.67‒3.78, P <0.001, Figure 4).
Furthermore, there was a evidence
of heterogeneity for ORR among
the included trials (Figure 4).
A sensitivity analysis indicated
that the results were not affected
by sequential exclusion of any
particular trial from all pooled
analysis.
Toxicity
Data concerning AEs were
e x t r a c t e d f r o m 11 t r i a l s ; a
summary of the drug-related
toxicities was shown in
Table 2. Overall, the pooled
OR of each kind of toxicity
indicated that a significant
increase associated with
gefitinib therapy was observed
for ashes, diarrhea, dry skin,
pruritus, paronychia, abnormal
hepatic function compared
to traditional chemotherapy.
C o n v e r s e l y, w e a l s o n o t e d
that gefitinib protected against
nausea, constipation, asthenic
condition, peripheral edema,
Figure 2. Comparison of the overall survival between gefitinib therapy and gefitinib-free therapy.
Figure 3. Comparison of the progression-free survival between gefitinib therapy and gefitinib-free fatigue, anemia, neutropenia,
therapy.
leukopenia, febrile neutropenia,
Figure 4. Comparison of the objective response rate between gefitinib therapy and gefitinib-free
alopecia, myalgia, neurotoxicity,
therapy.
arthralgia, sensory disturbance,
and thrombocytopenia, when compared to gefitinib-free
Figure 2).
therapy. Furthermore, we noted that heterogeneity among
trials was found in these analyses, possibly due to the
Progression-free survival
use of different agents at various dosages and the use of
Eleven trials including 5152 patients provided PFS results.
5. Chin Med J 2013;126 (17)
3352
Table 3. Subgroup analysis for the effect of Gefitinib therapy on OS and PFS
Variables
OS
Number of patients
≥1000
<1000
Median age
<64
≥64
Gender (male, %)
>65%
<65%
Control drug
Traditional chemotherapy
Placebo
Treatment status
First line
Second line
Follow-up
≥36 months
<36 months
Smoker
Never smoker
Current/former smoker
Racial
Asian
Non-Asian
Disease status (IIIB or IV)
≥90%
<90%
Pre-existent diseases
Adenocarcinoma
Non-adenocarcinoma
EGFR FISH
Positive
Negative
Jadad score
4
<4
PFS
Number of patients
≥1000
<1000
Mean age
<64
≥64
Gender (male, %)
>65%
<65%
Drug
Traditional chemotherapy
Placebo
Treatment status
First line
Second line
Follow-up
≥36 months
<36 months
Smoker
Never smoker
Current/former smoker
Racial
Asian
Non-Asian
Disease status (IIIB or IV)
≥90%
<90%
Pre-existent diseases
Adenocarcinoma
Non-adenocarcinoma
EGFR FISH
Positive
Negative
Jadad score
4
<4
Hazard ratio (HR)
P values
Heterogeneity (%)
P values for heterogeneity
0.95 (0.87−1.04)
0.90 (0.78−1.03)
0.266
0.110
16.1
32.2
0.304
0.171
0.92 (0.84−1.00)
0.96 (0.73−1.26)
0.061
0.761
36.1
19.5
0.141
0.289
0.95 (0.88−1.04)
0.90 (0.79−1.03)
0.282
0.126
0
39.5
0.414
0.128
0.97 (0.89−1.06)
0.85 (0.76−0.95)
0.517
0.004
7.7
0
0.369
0.397
0.94 (0.84−1.06)
0.90 (0.79−1.02)
0.319
0.085
11.9
40.0
0.333
0.125
0.90 (0.73−1.12)
0.94 (0.87−1.02)
0.345
0.124
59.6
0
0.042
0.666
0.76 (0.59−0.98)
−
0.034
−
19.0
−
0.291
−
0.91 (0.78−1.06)
0.87 (0.78−0.97)
0.216
0.015
48.5
0
0.084
0.409
0.88 (0.79−0.98)
0.96 (0.81−1.13)
0.025
0.593
0
62.6
0.964
0.030
0.85 (0.76−0.95)
−
0.005
−
0
−
0.599
−
1.14 (0.18−7.16)
0.89 (0.59−1.33)
0.14
0.59
87.9
0
0.004
0.539
0.93 (0.86−0.99)
0.94 (0.73−1.21)
0.031
0.646
0
55.2
0.505
0.063
0.88 (0.63−1.23)
0.68 (0.54−0.86)
0.447
0.001
92.8
83.8
<0.001
<0.001
0.70 (0.56−0.87)
0.79 (0.49−1.27)
0.002
0.329
89.4
83.6
<0.001
0.002
0.92 (0.65−1.29)
0.66 (0.54−0.81)
0.623
<0.001
82.5
82.3
0.003
<0.001
0.71 (0.56−0.91)
0.73 (0.61−0.89)
0.006
0.001
90.7
7.7
<0.001
0.339
0.70 (0.51−0.95)
0.75 (0.58−0.95)
0.024
0.017
90.9
79.6
<0.001
<0.001
0.60 (0.45−0.81)
0.88 (0.72−1.08)
0.001
0.228
86.2
78.5
<0.001
0.001
0.48 (0.33−0.70)
−
<0.001
−
0
−
0.832
−
0.62 (0.48−0.79)
0.83 (0.63−1.08)
<0.001
0.161
86.6
64.5
<0.001
0.037
0.66 (0.50−0.86)
0.81 (0.62−1.06)
0.002
0.128
87.4
80.8
<0.001
0.001
0.63 (0.42−0.93)
−
0.021
−
76
−
0.041
−
0.76 (0.22−2.65)
1.29 (0.53−3.15)
0.665
0.579
91.0
90.9
<0.001
<0.001
0.67 (0.50−0.88)
0.80 (0.62−1.03)
0.005
0.080
92.2
70.2
<0.001
0.009
6. Chinese Medical Journal 2013;126 (17)
different control arms. No other significant differences
were identified between the effect of gefitinib therapy and
control for adverse events.
Subgroup analysis
Subgroup analyses were carried out for overall survival and
progression free survival. Overall, we noted that gefitinib
therapy was associated with an improvement of the overall
survival when compared to placebo, never smoker, nonAsian, IIIB or IV ≥90%, patients with adenocarcinoma,
or Jadad score more than 3. Similarly, gefitinib therapy
produced a statistically significant improvement of PFS
when the number of patients was <1000, mean age <64,
the proportion of male <65%, compared to traditional
chemotherapy/placebo, first-line, second-line, followup more than 36 months, never smoker, Asian, IIIB or IV
≥90%, patients with adenocarcinoma, or Jadad score more
than 3.
Publication bias
We used Egger’s test25 to check for potential publication
bias, which showed no evidence of publication bias for
the outcomes of OS (P value for Egger’s test, 0.643) , PFS
(P value for Egger’s test, 0.170), and ORR (P value for
Egger’s test, 0.105).
DISCUSSION
The goal of the treatment of NSCLC was to prolong
survival time and prevent disease recurrence after therapy.5
Current third-line chemotherapy regimens provide little
benefit, and the small survival benefits obtained with
these treatment regimens are commonly balanced by their
substantial toxic effects. For patients who are refractory
to or intolerant of the current chemotherapy regimens,
currently treatment options are limited and new therapies
are needed.5,26,27
Several strategies were proposed to overcome this lowvalid. The most important one was that gefitinib therapy,
which was the first targeted drug to enter clinical use for the
treatment of lung cancer.28,29 However, several randomized
controlled trials reported an inconsistent conclusion on
OS, PFS, and ORR by gefitinib therapy in patients with
NSCLC as compared to the traditional chemotherapy or
placebo. Therefore, the goal of our research was to perform
a comprehensive, updated meta-analysis of randomized
controlled trials, which included all currently available
clinical trials.
This large quantitative review included 6844 patients
with NSCLC in 12 trials with a broad range of baseline
characteristics. The main finding of our research suggested
that gefitinib therapy had a clear effect on PFS and
ORR; furthermore, a sensitivity analysis and subgroup
analysis indicated that gefitinib therapy might contribute
an important role for OS. In addition, gefitinib was
associated with significantly less toxicity than traditional
chemotherapy and improved quality-of-life.
3353
In contrast with previous research, 30 these findings
supported that as an adjunctive therapy gefitinib does
not have significant benefits or harm in OS; however,
subgroup analysis demonstrated that gefitinib therapy had
a clear effect in the improvement of OS when compared
to placebo. The reason for these could be that although
traditional chemotherapy contributed a little, which are
commonly a balanced gefitinib effect on the overall
survival. Similarly, we also noted that gefitinib produced
an important role for OS in patients who previously never
smoke. The reason could be that patients currently smoking
or who were formerly smoking with impaired lung
function, could contribute an important role in the lessened
therapy effect by gefitinib. Furthermore, gefitinib produced
a clear effect when proportion of IIIB or IV ≥90%, and
patients with adenocarcinoma, the reason could be that
gefitinib has emerged as a new drug commonly used for
advanced NSCLC. Our research also supported that nonAsian patients gained more benefit from gefitinib in times
of treatment failure. These results are also consistent with
previous randomized controlled trials.
The results of our research demonstrated that gefitinib
yielded a statistically significant benefit in PFS as compared
to gefitinib-free therapy; however, it should be noted that
progression-free survival was not improved when the
number of patients was more than 1000, median age was
more than 64, the proportion of male was more than 65, the
follow-up time was less than 36 months, non-Asian, the
proportion of IIIB or IV was lesser than 90, EGFR FISH
positive or negative, Jadad score less than 4. The reason
could be that less trials reported progression-free survival
data in some subsets, while other reasons similarly to the
overall survival. In contrast with previous meta-analysis,
improvement in the objective response rate also detected
between gefitinib and gefitinib-free therapies. Previous
research31,32 indicated that gefitinib was active in NSCLC,
with confirmed objective response rates of 12%–18%. The
significant improvements in time to treatment failure and
objective response rate seen with gefitinib in our research
are consistent with these previous studies.
Some drug-related toxicity was significantly more frequent
in patients who received gefitinib therapy. We noted
that rashes, diarrhea, dry skin, pruritus, paronychia, and
abnormal hepatic function were more frequent in the
gefitinib therapy group. In addition, gefitinib also protected
against nausea, constipation, asthenia condition, peripheral
edema, fatigue, anemia, neutropenia, leucopenia, febrile
neutropenia, alopecia, myalgia, neurotoxicity, arthralgia,
sensory disturbance, and thrombocytopenia as compared
to traditional chemotherapy. We easily concluded that
gefitinib was a promising therapy in patients with NSCLC,
which contributed to less toxicity than the traditional
chemotherapy and significantly improved the quality-oflife.
Although the benefit of gefitinib therapy may be lessened or
balanced by some drug-related toxicity, however, gefitinib
7. Chin Med J 2013;126 (17)
3354
as an adjunctive therapy could improve PFS, ORR, and
could lessen drug-related toxicities compared to traditional
chemotherapy. In addition, we should considered patients’
baseline characteristics before any therapeutic decision is
made to ensure the patients with the best therapy.
The main purpose of our research was to present all
available evidence in a systematic, quantitative, and
unbiased fashion. The findings of this meta-analysis
suggested that gefitinib therapy produced a significant
improvement in the progression-free survival, objective
response rate, and it might also play an important role
in the overall survival. Compared to previous research,
our research provided a more detailed conclusion on OS
and drug-related toxicities information. As compared to
individual trials, our research provided a conclusion for
the effect of gefitinib therapy in patients with advanced
NSCLC.
The limitations of our research are as follows: (1)
although subgroup analysis suggested that gefitinib
significantly improved the OS and PFS for patients with
adenocarcinoma, however, these results may be variable
because of the small number of trials (only three trials)
that provided such a subset of survival data; (2) data on
quality of life were rarely available in these trials and no
conclusions could be drawn; (3) inherent assumptions made
for any meta-analysis, because the analysis used pooled
data either published or provided by individual study
authors, and individual patients survival data or original
data were unavailable, which restricted us from doing a
more detailed and relevant analysis and obtaining more
comprehensive results.
In conclusion, the findings of this study also supported
previous findings that the gefitinib therapy had a clear effect
on the PFS and ORR. A sensitivity analysis and subgroup
analysis also demonstrated that gefitinib therapy might
play an important role on the OS. Future focus will be on
the identification of predictive markers which may enable
treatments to be targeted to specific patient groups and
thereby translate it into improved outcomes. Furthermore,
subgroup analysis in individual trial needs a more detailed
and formulated report.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
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(Received October 23, 2012)
Edited by CUI Yi