scholarly journals Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303)

2010 ◽  
Vol 28 (22) ◽  
pp. 3617-3622 ◽  
Author(s):  
Hedy Lee Kindler ◽  
Donna Niedzwiecki ◽  
Donna Hollis ◽  
Susan Sutherland ◽  
Deborah Schrag ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Group B ◽  
Leukemia Group

Purpose The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients. Patients and Methods Eligible patients had no prior therapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, no tumor invasion of adjacent organs, and no increased bleeding risk. The primary end point was overall survival. Patients were stratified by performance status, extent of disease, and prior radiotherapy. Patients received gemcitabine at 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days. Results Between June 2004 and April 2006, 602 patients were enrolled onto the study and 535 were treated. Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo (P = .95). Median progression-free survival was 3.8 and 2.9 months, respectively (P = .07). Overall response rates were 13% and 10%, respectively. Patients with a performance status of 0, 1, and 2 survived a median of 7.9, 4.8, and 2.4 months, respectively. The only statistically significant differences in grades 3 and 4 toxicity occurred for hypertension (10% v 3%; P < .001) and proteinuria (5% v 1%; P = .002); venous thrombosis grade ≥ 3 was equivalent in both arms (14% and 15%, respectively). Conclusion The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients.

Modified FOLFIRINOX versus S-1 as second-line chemotherapy in patients with gemcitabine-failed metastatic pancreatic cancer: A randomized phase III trial (MPACA-3).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4119-4119
Author(s):  
Se-Il Go ◽  
Sang-Cheol Lee ◽  
Woo Kyun Bae ◽  
Dae Young Zang ◽  
Hyun Woo Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Phase Iii Trial

4119 Background: Modified FOLFIRINOX (mFOLFIRINOX) consisting of 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin has been assessed as second-line treatment of patients with advanced pancreatic cancer in retrospective and phase II studies. However, the result was not confirmed by randomized controlled trial. Methods: A randomized, open-label, phase III trial was conducted at 9 institutions in Korea. Patients with metastatic pancreatic adenocarcinoma (mPAC) and Eastern Cooperative Oncology Group performance status of 0-1 who failed to first-line gemcitabine-based chemotherapy were randomly assigned to receive mFOLFIRINOX or S-1. The primary endpoint was overall survival. Results: A total of 80 patients were enrolled from March 2017 to December 2019. The accrual of patients was early terminated due to clear difference of efficacy in the interim analysis and expectation of poor recruitment due to conflicting adjuvant regimens. Objective response and disease control rates were 15.4% vs. 2.4% ( p= 0.041) and 66.7% vs. 36.6% ( p= 0.007) in the mFOLFIRINOX and S-1 arms, respectively. The median progression-free survival was 5.2 and 2.2 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.002). The median overall survival was 9.2 and 4.9 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.048). The adjusted hazard ratio of the mFOLFIRINOX arm to the S-1 arm for overall survival was 0.402 (95% confidence interval 0.223-0.725, p= 0.002). All grade 3-4 adverse events occurred in 56.5% and 17.1% in the mFOLFIRINOX and S-1 arms, respectively ( p< 0.001). However, only one patient in each arm prematurely discontinued treatment due to toxicity and there was no treatment-related mortality in both arms. Minimally important differences in the health-related quality of life were not observed in both arms. Conclusions: mFOLFIRINOX as second-line treatment in mPAC patients failed to gemcitabine-based chemotherapy demonstrated a survival benefit versus S-1 alone with acceptable toxicities. Clinical trial information: KCT0003534.

Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group

2007 ◽  
Vol 25 (16) ◽  
pp. 2212-2217 ◽  
Author(s):  
Richard Herrmann ◽  
György Bodoky ◽  
Thomas Ruhstaller ◽  
Bengt Glimelius ◽  
Emilio Bajetta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Karnofsky Performance Score ◽  
Phase Iii Trial ◽  
Good Performance Status ◽  
Grade 3

PurposeThis phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2twice daily on days 1 to 14 plus Gem 1,000 mg/m2by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.ResultsA total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.ConclusionGemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Single-Agent Gemcitabine As First-Line Treatment of Patients With Advanced Pancreatic Cancer: The GIP-1 Study

2010 ◽  
Vol 28 (10) ◽  
pp. 1645-1651 ◽  
Author(s):  
Giuseppe Colucci ◽  
Roberto Labianca ◽  
Francesco Di Costanzo ◽  
Vittorio Gebbia ◽  
Giacomo Cartenì ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Line Treatment ◽  
First Line ◽  
Phase Iii Trial ◽  
First Line Treatment

PurposeSingle-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).Patients and MethodsPatients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) ≥ 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m2weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m2added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral α .05, 355 events were needed and 400 patients planned.ResultsFour hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS ≥ 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.ConclusionThe addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

2007 ◽  
Vol 25 (15) ◽  
pp. 1960-1966 ◽  
Author(s):  
Malcolm J. Moore ◽  
David Goldstein ◽  
John Hamm ◽  
Arie Figer ◽  
Joel R. Hecht ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Pancreatic Tumors ◽  
Double Blind ◽  
Phase Iii Trial

PurposePatients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival.ResultsA total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2.ConclusionTo our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (27) ◽  
pp. 4441-4447 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Richard Letourneau ◽  
Graydon Harker ◽  
Manuel Modiano ◽  
Herbert Hurwitz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Water Soluble ◽  
Phase Iii ◽  
Eligibility Criteria

Purpose Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted. Patients and Methods Eligibility criteria included Karnofsky performance status ≥ 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used. Results From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%). Conclusion Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer.

Meta-analysis of randomized phase II and phase III trials of gemcitabine with/without S-1 in Asian patients with advanced pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 311-311 ◽  
Author(s):  
Geoffrey Yuyat Ku ◽  
Benjamin Haaland ◽  
Tatsuya Ioka ◽  
Hiroyuki Isayama ◽  
Yousuke Nakai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Meta Analysis ◽  
Performance Status ◽  
Dihydropyrimidine Dehydrogenase ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Asian Patients ◽  
Ecog Ps

311 Background: Advanced pancreatic cancer (PC) is a virulent disease, where gemcitabine is considered the standard-of-care. A recent phase III evaluation demonstrated superiority of FOLFIRINOX (bolus and infusional 5-fluorouracil (FU), irinotecan, oxaliplatin) in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1. Recently, three studies were presented in abstract form, comparing gemcitabine/S-1 (GS) to gemcitabine. S-1 is a mixture of tegafur (an oral 5-FU prodrug), a dihydropyrimidine dehydrogenase inhibitor and an agent designed to reduce the gastrointestinal toxicity of 5-FU. All three trials demonstrated significant improvements in progression-free survival (PFS) while one study also showed a statistically significant improvement in overall survival (OS). Methods: We performed a meta-analysis of the three trials. Results: Seven hundred and seventy patients were randomized to receive GS vs. gemcitabine; 75% had metastatic disease and 65% had an ECOG PS of 0. GS was associated with superior RR (hazard ratio (HR) 0.348, p=3.06×10-7), PFS (HR 0.64, p=7.26×10-9) and OS (HR 0.79, p=2.47×10-2) compared to gemcitabine. Patients receiving GS were more likely to experience nausea, diarrhea, rash and stomatitis (mostly grade 1/2); neutropenic fever occurred in <2% of patients. One study demonstrated superior quality-of-life for GS. Conclusions: GS should be considered a first-line option for the treatment of advanced PC in Asian patients. This regimen should serve as the reference for future trials and comparison with FOLFIRINOX in patients with ECOG PS ≤1 is warranted.

Phase II Trial of Bevacizumab Plus Gemcitabine in Patients With Advanced Pancreatic Cancer

2005 ◽  
Vol 23 (31) ◽  
pp. 8033-8040 ◽  
Author(s):  
Hedy L. Kindler ◽  
Gregory Friberg ◽  
Deepti A. Singh ◽  
Gershon Locker ◽  
Sreenivasa Nattam ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Tumor Measurements ◽  
Grade 3 ◽  
Group B ◽  
Endothelial Growth Factor

Purpose Vascular endothelial growth factor (VEGF) plays a key role in the biology and prognosis of pancreatic cancer. Inhibitors of VEGF suppress the growth of pancreatic cancer in preclinical models. The objectives of this phase II study were to assess the response rate and overall survival of pancreatic cancer patients who received gemcitabine with the recombinant humanized anti-VEGF monoclonal antibody bevacizumab. Patients and Methods Patients with previously untreated advanced pancreatic cancer received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Bevacizumab, 10 mg/kg, was administered after gemcitabine on days 1 and 15. Tumor measurements were assessed every two cycles. Plasma VEGF levels were obtained pretreatment. Results Fifty-two patients were enrolled at seven centers between November 2001 and March 2004. All patients had metastatic disease, and 83% had liver metastases. Eleven patients (21%) had confirmed partial responses, and 24 (46%) had stable disease. The 6-month survival rate was 77%. Median survival was 8.8 months; median progression-free survival was 5.4 months. Pretreatment plasma VEGF levels did not correlate with outcome. Grade 3 and 4 toxicities included hypertension in 19% of the patients, thrombosis in 13%, visceral perforation in 8%, and bleeding in 2%. Conclusion The combination of bevacizumab plus gemcitabine is active in advanced pancreatic cancer patients. Additional study is warranted. A randomized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo is ongoing in the Cancer and Leukemia Group B.

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