Timing of first-line cancer treatments – Early versus late – A systematic review of phase III randomized trials

2010 ◽  
Vol 36 (8) ◽  
pp. 621-628 ◽  
Author(s):  
A.R. Mhaskar ◽  
G. Quinn ◽  
S. Vadaparampil ◽  
B. Djulbegovic ◽  
C.K. Gwede ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Trials ◽  
Phase Iii ◽  
First Line ◽  
Cancer Treatments

Chemoradiotherapy in the Management of Locally Advanced Pancreatic Carcinoma: A Qualitative Systematic Review

2009 ◽  
Vol 27 (13) ◽  
pp. 2269-2277 ◽  
Author(s):  
Florence Huguet ◽  
Nicolas Girard ◽  
Clotilde Séblain-El Guerche ◽  
Christophe Hennequin ◽  
Françoise Mornex ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Carcinoma ◽  
Induction Chemotherapy ◽  
Randomized Trials ◽  
Locally Advanced ◽  
Phase Iii ◽  
Level Of Evidence ◽  
Qualitative Systematic Review ◽  
Survival Level

PurposePancreatic carcinoma is one of the leading causes of cancer-related mortality. At time of diagnosis, 30% of patients present with a locally advanced unresectable but nonmetastatic pancreatic carcinoma (LAPC). The French program Standards, Options, and Recommendations was promoted to conduct a qualitative systematic review to evaluate the role of radiotherapy in patients with LAPC.MethodsA search to identify eligible studies was undertaken using the MEDLINE database. All phase III randomized trials and systematic reviews evaluating the role of radiotherapy in LAPC were included, together with some noncontrolled studies if no phase III trials were retrieved. The quality and clinical relevance of the studies were evaluated using validated checklists, which allowed associating each result with a level of evidence.ResultsTwenty-one studies were included, as follows: two meta-analyses, 13 randomized trials, and six nonrandomized trials. Chemoradiotherapy increases overall survival when compared with best supportive care (level of evidence C) or with exclusive radiotherapy (level B1), but is more toxic (level B1). Chemoradiotherapy is not superior to chemotherapy in terms of survival (level B1) and increases toxicity (level A). Recent data favor limited irradiation to the tumor volume (level C). Fluorouracil is still the reference chemotherapy in association with radiotherapy (level B1). Induction chemotherapy before chemoradiotherapy improves survival (level C).ConclusionNo standard treatment exists, but there are two options for treatment of LAPC; these are gemcitabine-based chemotherapy and chemoradiotherapy. Induction chemotherapy followed by a chemoradiotherapy is a promising strategy for selection of patients without early metastatic/progressing disease.

A systematic review of post first-line treatments for advanced gastrointestinal stromal tumor (GIST): Direct pairwise meta-analyses and indirect comparisons.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 195-195
Author(s):  
Keya Shah ◽  
Kelvin K. Chan ◽  
Yoo-Joung Ko
Keyword(s):  
Systematic Review ◽  
Indirect Comparison ◽  
Phase Iii ◽  
Controlled Trials ◽  
First Line ◽  
The Third ◽  
Third Line ◽  
Line Setting ◽  
Meta Analyses ◽  
Indirect Comparisons

195 Background: Treatment for metatastatic or unresectable GIST is with imatinib. The majority of patients eventually acquire imatinib resistance, prompting the development of a growing number of agents as post-first-line treatment. Currently no studies directly compare these treatments. Methods: A systematic review was performed through MEDLINE, EMBASE, CENTRAL, and ASCO meeting abstracts up to July 2014 to identify randomized controlled trials that included GIST patients who were previously treated with a first-line chemotherapy for advanced disease. Progression-free survival (PFS) and overall survival (OS) with 95% credible regions were extracted using the Parmar method. Direct pairwise meta-analyses and indirect comparisons using the Bucher method were performed. Results: Four studies were identified for the systematic review. 1 study (n=312) showed that sunitinib in the second-line setting (vs. placebo) improved PFS but not OS. 3 studies (n=528) examined the third-line setting (imatinib resumption vs. placebo; regorafenib vs. placebo; nilotinib vs. best supportive care with or without imatinib or sunitinib). Of the 3 third-line studies, there was significant heterogeneity between placebo-controlled trials and the non-placebo controlled trial (I2= 98%). Direct pairwise meta-analysis using random-effects of the 2 placebo-controlled studies showed that the PFS hazard ratio (HR) was 0.63 (0.22-0.61, p=0.0001), whereas the PFS HR for the non-placebo controlled study was 0.90 (0.65-1.26, p=0.56). These 2 HRs are different statistically (interaction: p=0.002). Indirect comparisons of imatinib resumption vs. regorafenib suggested that the PFS HR was 0.59 (0.31-1.11, p=0.10), trending in favor of regorafenib. OS HRs were not significant for direct or indirect comparison in the third-line setting. Conclusions: The number and size of completed phase III studies and the lack of a standard comparator arm limit the use of direct and indirect comparison methods to determine the best therapeutic option for patients who have progressed on imatinib. At this time, clinicians should interpret the available evidence at an individual level.

A Phase IIIb Study of Rituximab Maintenance Therapy in Patients with Follicular Non-Hodgkin’s Lymphoma Who Have Responded to Induction Therapy - MAXIMA-Protocol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4706-4706 ◽  
Author(s):  
Manfred Hensel ◽  
Mathias Witzens-Harig ◽  
Peter Dreger ◽  
Anthony D. Ho ◽  
Daniel Thurley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Randomized Trials ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract Five randomized trials (four Phase III and one phase II) have confirmed that rituximab maintenance therapy provides clinical meaningful improvements in terms of Progression Free Survival, Event Free Survival and response duration for patients. Two studies have also found an overall survival advantage for rituximab maintenance therapy (Hoechster et al. 2005, van Oers et al. 2005) and a third study could demonstrate a strong trend towards overall survival advantage (Dreyling et al. 2006). A Cochrane meta-analysis of several randomised Phase III trials (Schulz et al. 2005) demonstrated that rituximab plus-chemotherapy for first-line treatment of Follicular Lymphoma is superior to chemotherapy alone and significantly prolongs overall survival. To further broaden the available basis for maintenance treatment in the first-line and relapsed setting, the MAXIMA (MAintenance rituXImab in Follicular LymphoMA) trial has been started in August 2006 and will last 5 years. Patients with first line or relapsed/refractory advanced Follicular Lymphoma are included in this trial. In total 500 patients are planned for this international trial running in 23 countries. Patients who achieve a Complete Remission, Complete Remission unconfirmed or Partial Remission after rituximab containing induction therapy (rituximab with or without chemotherapy) are eligible to enter the study to receive rituximab maintenance therapy administered at the standard dose of 375 mg/m2 every 2 months for 2 years. This regimen is also investigated in the ongoing PRIMA study, and also in an ongoing SAKK study which investigates the benefit of rituximab maintenance therapy for up to five years. The previous five randomized trials did not detect significant safety issues for rituximab maintenance therapy. The main objective of the MAXIMA trial is to confirm this safety data in a wider patient population. Secondary objectives of the study include standard time dependent parameters (PFS, EF, OS). In addition, the effect of rituximab maintenance therapy on improving response quality (PR =>CR) after induction therapy will be evaluated.

scholarly journals High-Dose Chemotherapy in Adult Patients with Germ Cell Tumors

2003 ◽  
Vol 10 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Ugo De Giorgi ◽  
Giorgio Papiani ◽  
Giuseppe Severini ◽  
Giammaria Fiorentini ◽  
Maurizio Marangolo ◽  
...  
Keyword(s):  
Germ Cell ◽  
Poor Prognosis ◽  
Randomized Trials ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
High Dose ◽  
First Line ◽  
Line Setting

Background Approximately 80% of patients with advanced germ cell tumors (GCTs) can be cured with cisplatin-based chemotherapy. Patients with poor-prognosis disease have a cure rate of only 50%, whereas patients with first relapse have only a 25% chance of prolonged survival and potential cure following standard therapy. High-dose chemotherapy (HDC) is being investigated in patients with GCTs to improve the results of salvage treatment and in first-line setting for poor prognosis disease. Methods The authors review the results of the clinical trials that have evaluated the role of HDC in GCT patients. Data were obtained using a computer-assisted MEDLINE search, and meeting abstracts with clinical relevance in this field were hand-searched. Open randomized phase III studies are described and examined. Results Several phase II studies have shown a possible benefit for patients with recurrent disease, but the preliminary results of a phase III randomized trial did not demonstrate a survival advantage for HDC after three courses of standard-dose chemotherapy in the salvage therapy of patients in whom first-line treatment has failed. Three prospective, randomized trials are evaluating the role of HDC in a first-line setting. Conclusions New HDC strategies are emerging, involving new drugs (eg, paclitaxel), intensive induction regimens, and upfront and/or multiple courses of HDC. The evaluation of mature data of randomized trials will better define the role of HDC in this disease.

Meta-analysis of randomized trials comparing cisplatin versus carboplatin-based regimens for the first-line therapy of metastatic transitional cell carcinoma of the urothelium (TCCU).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 247-247
Author(s):  
G. Sonpavde ◽  
M. D. Galsky ◽  
G. J. Chen ◽  
J. Bellmunt ◽  
B. J. Roth ◽  
...  
Keyword(s):  
Survival Data ◽  
English Language ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Transitional Cell ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Standard ◽  
First Line Treatment

247 Background: Cisplatin-based chemotherapy is the first-line treatment standard for metastatic TCCU, although carboplatin is substituted for cisplatin-ineligibility, tolerability, and ease of administration. Since definitive data comparing cisplatin- versus carboplatin-based chemotherapy are lacking, a meta-analysis of published randomized trials was performed. Methods: PubMed was searched for articles published in the English language from 1966 until 2010 and abstracts presented at the American Society of Clinical Oncology Annual Meeting between 2000 and 2010 were searched to identify relevant trials. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in cisplatin-eligible patients with metastatic TCCU. Individual patient data were not available and progression and survival data were inconsistently reported. Therefore, the analysis focused on overall (OR) and complete response (CR). The Mantel-Haenszel method was used for combining trials and calculating pooled risk ratios (RR). Results: A total of 286 patients with metastatic TCCU from 4 randomized trials (3 phase II and 1 phase III trial) were included. Chemotherapy regimens included MVEC (methotrexate, vinblastine, epirubicin, cisplatin) vs. MVECa (methotrexate, vinblastine, epirubicin, carboplatin), MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) vs. MCAVI (methotrexate, carboplatin, vinblastine), MVAC vs. paclitaxel plus carboplatin, and gemcitabine plus cisplatin vs. gemcitabine plus carboplatin. Cisplatin-based chemotherapy was associated with a significant improvement in the likelihood of CR (RR=3.973 [95%CI: 1.562 – 10.110], p =0.004) and OR (RR=1.336 [95%CI: 1.043 – 1.712], p=0.025). Conclusions: Cisplatin-based as compared with carboplatin-based combination chemotherapy significantly increases the likelihoods of both OR and CR, in patients with metastatic TCCU. In the absence of definitive phase 3 trials, these results support cisplatin-based regimens as the preferred first-line treatment for cisplatin-eligible patients with metastatic TCCU. No significant financial relationships to disclose.

Efficacy and safety of sunitinib and everolimus as front-line treatment for nonclear cell RCC: A pooled-analysis from randomized trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16069-e16069
Author(s):  
Carlo Messina ◽  
Marco Messina
Keyword(s):  
Randomized Trials ◽  
Statistical Significance ◽  
Prospective Trial ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Setting ◽  
Prospective Trials ◽  
Grade 3

e16069 Background: Non-clear Renal cell carcinoma (non-ccRCC) accounts for about 25% of all RCC and generally is responsible for a poorer outcome in metastatic setting. Optimal treatment for patients with metastatic non-ccRCC has not been established yet; therefore Sunitinib and Everolimus still represent two feasible options as frontline therapy, given the results reported from single-arm trials and expanded access studies. Hence, we provided a pooled analysis from prospective randomized trials to evaluate the benefit and risks of these therapies for patients with metastatic-non-ccRCC. Methods: A systematic search of literature was carried out using Medline, Embase, ESMO and ASCO library with no data restriction up to December 2016, to identify relevant studies on this topic. Eligible studies had to fulfill the following criteria: randomized prospective trial comparing the efficacy of Sunitninb and Everolimus as first line therapy in patients with m-non-ccRCC. Studies excluded: non-randomized prospective trials, subgroup analysis data deriving from randomized prospective trials carried out on metastatic ccRCC population. No language restriction was applied. Data were pooled using RevMan 5.3 software. Results: The literature search identified 29 potential titles and abstracts of whom only 2, recruiting a total of 176 metastatic-non ccRCC patients (Sunitinib: 84, Everolimus: 92), fulfilled our eligible criteria and were included in the pooled analysis. A trend towards better outcome in terms of PFS and OS was reported among patients with non-cc RCC enrolled in Sunitinib arm. Sunitinib vs Everolimus: PFS [HR]:0,83 [0,38-1,78]; OS [HR]: 0,67 [0,37-1,21]. Moreover Sunitinib was associated with more Grade 3-4 adverse events HR: 3.06 [1,60-5,84]. Conclusions: This pooled analysis reported a trend towards favoring Sunitinib versus Everolimus for the first line treatment of patients with metastatic non-ccRCC, although statistical significance was not reached. Sutent was associated with more Grade 3-4 toxicieties. Further prospective randomized phase III trials are required to clarify the better therapeutic option for this subset of patients.

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