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Background

E6201: Phase III Trial of Gemcitabine (30-minute infusion) vs Gemcitabine (fixed-dose-rate infusion) vs Gemcitabine + Oxaliplatin for Patients with Advanced Pancreatic Cancer.

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Background

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  1. E6201: Phase III Trial of Gemcitabine (30-minute infusion) vs Gemcitabine (fixed-dose-rate infusion) vs Gemcitabine + Oxaliplatin for Patients with Advanced Pancreatic Cancer Elizabeth Poplin MD, Donna Levy MS, Jordan Berlin MD, Mace Rothenberg MD, Peter O’Dwyer MD, David Cella MD, Edith Mitchell MD, Steve Alberts MDand Al B. Benson III.

  2. Background

  3. E6201: Objectives • Primary: • To determine whether either FDR GEM or GEMOX increases survival compared with standard 30-min infusion GEM. • Secondary: • Toxicity, • response rates, • progression-free survival, and • QOL Poplin, E. ASCO 2006

  4. E6201: Study Design • Stratification factors: • ECOG PS: 0 –1 vs 2 • Locally advanced vs metastatic disease Gem 1000mg/m2/ 30 minutes n=279 Randomization n=832 Gem FDR: 1500 mg/m2/150 minutes n=277 Gem 1000mg/m2/100 minutes, day 1 Oxaliplatin 100mg/m2, day 2 n=276 Poplin, E. ASCO 2006

  5. Statistical Design: Assumes median survival of 6 mo for standard Gemcitabine and 8mo for FDR Gem and GEMOX Designed to detect >33% difference in survival (hazard ratio <0.75) -81% power -significance level of 0.025 in a two-sided test for each of the two primary comparisons

  6. Study Conduct Activated March 26, 2003 Terminated March 16, 2005 Final Accrual:832 Patients Contributors:ECOG, NCCTG, CTSU

  7. E6201: Eligibility • Pancreatic adenocarcinoma or poorly differentiated carcinoma, • measurable and/or nonmeasurable, • locally advanced or metastatic • No prior therapy for metastatic disease, • prior adjuvant chemotherapy/radiotherapy was permitted • No prior GEM or oxaliplatin. • ECOG Performance Status of 0-2 • 4. Adequate organ function: • 5. No symptomatic ( >gr2) peripheral neuropathy • 6. Other standard eligibility Poplin, E. ASCO 2006

  8. E6201:Treatment Arms ARM A: GEM 1000 mg/m2/ 30 min q wk x 7 of 8 weeks,  GEM 1000 mg/m2/ 30 min q wk x 3 of 4 weeks(GEM) ARM B: GEM 1500 mg/m2/150 min q wk x 3 of 4 weeks (FDR) ARM C: GEM 1000 mg/m2/100 min day 1, and Oxaliplatin 100 mg/m2/120 min day 2 repeated every 14 days. (GEMOX) Poplin, E. ASCO 2006

  9. E6201 Patient Entry Characteristics: Total: 832 88% PS 0-1 12% PS 2 88% metastatic 12% locally advanced GEM:279 FDR:277 GEMOX:276 Median follow-up 12.2 mo 725 patients expired @5-25-06 Poplin, E. ASCO 2006

  10. E6201: Patient Characteristics Poplin, E. ASCO 2006

  11. E6201: Toxicity: Grade 3/4 Poplin, E. ASCO 2006

  12. Off-treatment reasons (prelim) Poplin, E. ASCO 2006

  13. E6201: Response (preliminary) Poplin, E. ASCO 2006

  14. Survival Months,Median (CI) %1-year(SE) GEM 4.9 (4.5-5.6) 17%(2) FDR GEM 6.0 (5.4-6.9) 21%(3) GEMOX 5.9 (5.1-6.8) 21%(3) Poplin, E. ASCO 2006

  15. E6201: Overall Survival By Treatment GEM 4.9 (4.5-5.6) 17% FDR GEM 6.0 (5.4-6.9) 21% GEMOX 5.9 (5.1-6.8) 21% GEMOX GEM FDR Poplin, ASCO, 2006

  16. E6201: Survival Hazard Ratios Neither experimental treatment succeeded in achieving the hazard ratio goal of <0.75 or the required p=.025. Poplin, ASCO, 2006

  17. Survival by disease extent Locally advanced 9.1 mo Locally advanced 9.1 mo P=.0001 Metastatic5.4 mo mo P+.00 Poplin, ASCO, 2006

  18. Conclusions: • Neither FDR GEM nor GEMOX proved statistically significantly better than standard GEM. Both had approximately one month longer median survival than standard GEM. • The survival outcome for standard GEM is consistent, though slightly shorter than, other large studies showing survival of 5-6 months. Neither FDR nor GEMOX had survival durations as long as previously reported in smaller studies. Poplin, ASCO,2006

  19. Conclusions: • Both experimental arms had increased toxicity: increased myelosuppression with FDR GEM and increased N/V and neuropathy with GEMOX. • Thus, E6201 adds to multiple prior studies that demonstrate either no or modest overall benefit with the addition of a second chemotherapy agent to gemcitabine. FDR GEM, with higher dose and longer duration, is of limited benefit. Poplin, ASCO,2006

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