A PHASE-I TRIAL OF INTRAVENOUS BROMODEOXYURIDINE AND RADIATION-THERAPY FOR PANCREATIC-CANCER

Purpose: Improved radiosensitization may lead to improved results of t reatment for pancreatic cancer. This Phase I trial was designed to det ermine the maximum tolerable dose of intravenous bromodeoxyuridine (Br dUrd) when given in an alternating weekly fashion with radiation thera py for patients with pancreatic cancer. Methods and Materials: Patient s with resected or locally unresectable pancreatic cancer were eligibl e if distant metastases were not present. A continuous intravenous inf usion of BrdUrd was given on weeks 1, 3, 5, and 7. Twice a day radiati on therapy (1.5 Gy per fraction) was given on weeks 2, 4, 6, and 8 to the pancreas/pancreatic bed (total dose 60 Gy) and draining regional l ymph nodes (total dose 45 Gy). The starting dose of BrdUrd was 800 mg/ m(2)/day with a planned escalation to 1000 mg/m(2)/day if at least six out of eight patients were without Grade greater than or equal to 3 t oxicity. Patients were assessed weekly for toxicity, and were followed every 3 months after treatment for complications and survival. Result s: Fifteen patients with resected (six) or unresectable (nine) pancrea tic cancer were enrolled. One patient failed to complete therapy due t o tumor progression. One of 11 patients treated with 800 mg/m(2)/day h ad a Grade 3 toxicity, while Grade 3 or 4 toxicity was found in all 3 patients receiving 1000 mg/m(2)/day. The dose-limiting toxicities were hematologic. The acute gastrointestinal toxicity was minimal. Two pat ients, including one with unresectable disease, were without evidence of disease during exploration for complications (ulcer, small bowel ob struction). Conclusions: The recommended dose of BrdUrd for Phase II s tudy is 800 mg/m(2)/day. The gastrointestinal mucosa did not appear to be sensitized by this method of BrdUrd administration. The presence o f a pathologic complete response is encouraging. Further improvements in radiosensitization are possible and may lead to improved local cont rol. (C) 1997 Elsevier Science Inc.