A phase I study of hypofractionated radiotherapy followed by systemic chemotherapy of full-dose gemcitabine in patients with unresectable locally advanced pancreatic carcinoma

Abstract

4221 Background: Full-dose gemcitabine cannot be used for concurrent chemoradiotherapy with gemcitabine in patients with locally advanced pancreatic carcinoma (LAPC) because of the toxicity. Hypofractionated radiotherapy (HFRT) can shorten the irradiation period and allow systemic chemotherapy of full-dose gemcitabine to be started earlier. The purpose of this study was to determine the feasible dose of HFRT that could be followed by full-dose gemcitabine in such patients. Methods: Nine patients with LAPC histologically confirmed as adenocarcinoma were enrolled in this phase I study. Three patients received HFRT at 45 Gy in 15 fractions (level 1) and six at 40 Gy in 8 fractions (level 2) in a week. Gemcitabine chemotherapy was started 3 months after the start of irradiation and was administered as a 30-minute intravenous infusion of a dose of 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Planning target volume encompasses primary tumor plus margin, and no elective nodal area was irradiated. Results: No patients experienced dose-limiting toxicity or grade 4 toxicity at either level of HFRT. All three patients treated at 45 Gy in 15 fractions received gemcitabine chemotherapy on schedule, and only one of the three had grade 3 nausea, vomiting, anorexia, and anemia during chemotherapy. However, at 40 Gy in 8 fractions grade 3 nausea and anorexia was observed in all 6 patients and grade 2 duodenal ulcer in 2 patients, and gemcitabine chemotherapy could not start on schedule in 4 of the 6 patients because of anorexia. Three of the 4 patients treated with 40 Gy in 8 fractions who received chemotherapy developed grade 3 toxicities: leukocytopenia in 4, anemia in 3, anorexia in 2, thrombocytopenia in 1, and nausea in 1. There was no CR or PR in the 7 evaluable patients; 2 of them had MR, 5 had SD. The median progression-free survival time was 4.9 months, and the median overall survival time was 7.5 months. Conclusions: HFRT with 40 Gy in 8 fractions was tolerable, but it is not recommended as radiotherapy for chemoradiotherapy with sequential full-dose gemcitabine. No significant financial relationships to disclose.