Estimating optimal dose of twice-weekly gemcitabine for concurrent chemoradiotherapy in unresectable pancreatic carcinoma: mature results of GEMRT-01 Phase I trial.

Abstract

To accurately determine the maximal tolerated dose, feasibility, and antitumor activity of concurrent chemoradiotherapy including twice-weekly gemcitabine in patients with unresectable pancreatic adenocarcinoma. Eligible patients with histologically proven adenocarcinoma of the pancreas were included in this Phase I trial. Radiotherapy was delivered to a total dose of 50 Gy. Concurrent chemotherapy with twice-weekly gemcitabine was administered during the 5 weeks of radiotherapy, from an initial dose of 30 mg/m(2). The gemcitabine doses were escalated in 10-mg/m(2) increments in a three-plus-three design, until dose-limiting toxicities were observed. A total of 35 patients were included in the trial. The feasibility of chemoradiotherapy was high, because all the patients received the planned total radiation dose, and 26 patients (74%) received > or = 70% of the planned chemotherapy dose. The mean total delivered dose of gemcitabine was 417 mg/m(2) (i.e., 77% of the prescribed dose). The maximal tolerated dose of twice-weekly gemcitabine was 70 mg/m(2). Of the 35 patients, 13 had a partial response (37%) and 21 had stable disease (60%). Overall, the median survival and the 6-, 12-, and 18-month survival rates were 10.6 months and 82%, 31%, and 11%, respectively. Survival was significantly longer in patients with an initial performance status of 0 or 1 (p = .004). Our mature data have indicated that gemcitabine doses can be increased < or = 70 mg/m(2), when delivered twice-weekly with concurrent radiotherapy. This combination shows promises to achieve better recurrence-free and overall survival. These results will serve as a basis for further implementation of the multimodal treatment of locally advanced pancreatic carcinoma.