Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group

Abstract

Purpose: Single-agent gemcitabine (GEM) is standard treatment of metastatic pancreatic cancer. Fixed-dose rate (FDR) GEM and GEM plus oxaliplatin have shown promise in early clinical trials. E6201 was designed to compare overall survival (OS) of standard weekly GEM 1,000 mg/m(2)/30 minutes versus GEM FDR 1,500 mg/m(2)/150 minutes or GEM 1,000 mg/m(2)/100 minutes/day 1 plus oxaliplatin 100 mg/m(2)/day 2 every 14 days (GEMOX).

Methods: This trial included patients with metastatic or locally advanced pancreatic cancer, normal organ function, and performance status of 0 to 2. The study was designed to detect a 33% difference in median survival (hazard ratio [HR] < or = 0.75 for either of the experimental arms) with 81% power while maintaining a significance level of 2.5% in a two-sided test for each of the two primary comparisons.

Results: Eight hundred thirty-two patients were enrolled. The median survival and 1-year survival were 4.9 months (95% CI, 4.5 to 5.6) and 16% for GEM, 6.2 months (95% CI, 5.4 to 6.9), and 21% for GEM FDR (HR, 0.83; stratified log-rank P = .04), and 5.7 months (95% CI, 4.9 to 6.5) and 21% for GEMOX (HR, 0.88; stratified log-rank P = .22). Neither of these differences met the prespecified criteria for significance. Survival was 9.2 months for patients with locally advanced disease, and 5.4 months for those with metastatic disease. Grade 3/4 neutropenia and thrombocytopenia were greatest with GEM FDR. GEMOX caused higher rates of nausea, vomiting, and neuropathy.

Conclusion: Neither GEM FDR nor GEMOX resulted in substantially improved survival or symptom benefit over standard GEM in patients with advanced pancreatic cancer.

Fig 1.

CONSORT diagram. (*) One patient, case 62256, withdrew consent, did not receive allocated intervention, and was lost to follow-up. GEM, gemcitabine; GEM FDR, gemcitabine fixed-dose rate.

Fig 2.

Overall survival. GEM, gemcitabine; GEM FDR, gemcitabine fixed-dose rate; GEMOX, gemcitabine 1,000 mg/m²/100 minutes/day 1 plus oxaliplatin 100 mg/m²/day 2 every 14 days.

Fig 3.

Progression-free survival. GEM, gemcitabine; GEM FDR, gemcitabine fixed-dose rate; GEMOX, gemcitabine 1,000 mg/m²/100 minutes/day 1 plus oxaliplatin 100 mg/m²/day 2 every 14 days.