Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG 0506

Abstract

e15578 Background: Fluorouracil (5-FU) chemoradiotherapy has been accepted as standard care for locally advanced pancreatic cancer (LAPC); however, it has not been shown to be superior to chemotherapy alone in gemcitabine (Gem) era. The present multicenter phase II study was conducted to evaluate the efficacy and the safety for the screening of Gem monotherapy against LAPC. Methods: Eligibility criteria included the following: patients (pts) with histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma, pts with UICC clinical stage III (T4N0–1 and M0), all lesions are assumed to be included in the radiation field of 15 cm square, age 20 or older, no prior treatment for LAPC, ECOG performance status of 0, 1 or 2, and adequate organ function. Gem was given intravenously at a dose of 1,000 mg/m2 over 30 minutes on days 1, 8 and 15, repeated every 4 weeks until disease progression. The primary endpoint was %1-year overall survival. A sample size of 50 was required with one-sided alpha of 0.20, beta of 0.10, expected %1-year survival of 40% and threshold %1-year survival of 25%. Results: Between Jan. 06 and Feb. 07, 50 pts from 14 institutions were registered. Patient characteristics were: median age; 67.5 (45–80), male/female; 35/15, PS 0/1/2; 30/20/0, pancreatic head/body-tail; 26/24. The major grade 3–4 adverse events were neutropenia (62%), leucopenia (32%), thrombocytopenia (18%), fatigue (12%), infection-biliary tree (10%), anorexia (8%), and nausea (6%). Hematological toxicity was mostly transient and there was no episode of infection with grade 3–4 neutropenia. There were no treatment-related deaths during the study. Serum CA 19–9 level was reduced by >50% in 37.5% of 40 pts with baseline CA19–9 >100U/ml. Up to the final follow-up in Apr. 08, the median overall survival was 1.25 years (95% CI, 1.06–1.71 years) with a %1-year survival of 64.8% (95% CI, 49.6–76.4%), and the null hypothesis (%1-y survival=25%) was rejected (p<0.0001). Conclusions: Gem monotherapy demonstrated far better survival than historical data of 5-FU chemoradiotherapy in LAPC pts with mild toxicities. In future randomized trial, we will select Gem chemotherapy as a referential arm to compare with the chemoradiotherapy regimen which is under phase II evaluation for LAPC. No significant financial relationships to disclose.