Phase II study of oxaliplatin (OX), 5-fluorouracil (5-FU), and radiation therapy (RT) followed by gemcitabine (GEM) in patients with unresectable pancreatic cancer

Abstract

15553 Background: Synergistic cytotoxicity with combinations of OX and 5-FU have been observed in a number of tumor systems. Both drugs have known radiosensitizing properties. This phase II study was conducted to evaluate the efficacy of concomitant 5-FU, OX and RT followed by GEM in patients (pts) with unresectable pancreatic cancer. Methods: Pts with unresectable non-metastatic invasive ductal pancreatic cancer with ECOG performance status of 0–1 were eligible. Surgical staging was not required. Pts received continuous infusion 5-FU 180 mg/m2 throughout RT and OX 85 mg/m2 on days 1, 15, 29 of RT by intravenous infusion. RT consisted of 45 Gy to the tumor and regional nodes followed by a 5.4 Gy boost to the gross tumor using conformal techniques and 1.8 Gy fractions. Upon completion of RT, patients received weekly GEM 1,000 mg/m2, two weeks out of three for 4 cycles. The primary endpoint was survival (OS) at one year with secondary endpoints of median survival, time to progression (TTP) and toxicity. Results: 53 eligible pts were enrolled in 14 mos. M:F- 30:23 with a median age of 65 (range: 31- 80). Median follow-up is 21.6 months (range: 14.3 - 29.7), with 9 pts still alive. The confirmed response rate is 6% (3 PR, 0 CR). Median TTP 7.1 mos (95% CI: 4.9–9.0), 12-month survival 34% (95% CI: 20–63%) and median survival 9.3 mos (95% CI: 5.9–11.4) were observed. Fifty (94%) and 10 (19%) pts experienced at least one grade 3+ or grade 4+ AE, respectively, with 1 pt (2%) death due to a cardiovascular event possibly related to protocol therapy. Frequently occurring maximum grade 3/4 AEs (regardless of attribution) are shown in the Table below: Conclusions: These results do not suggest an efficacy benefit for this combined modality therapy regimen. Toxicity results are similar to those seen with other regimens. Future studies will focus on the addition of novel agents in addition to RT in this setting. Type Grade 3 % Grade 4 % Type Grade 3% Grade 4% Leukopenia 26% 2% Hypokalemia 9% 2% Neutropenia 25% 2% Nausea 28% 0% Upper GI Hemorrhage 0% 4% Vasc Access Complications 0% 4% Vomiting 17% 0% Fatigue 36% 2% Hyperglycemia 9% 2% Anorexia 28% 0% Bilirubin 11% 2% Hypotension 4% 2% Dehydration 9% 2% Diarrhea 21% 0% Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis