Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer

Purpose: The primary objective of this phase I trial was to determine the m aximum-tolerated dose of radiation that could be delivered to the primary t umor concurrent with full-dose gemcitabine in patients with advanced pancre atic cancer. Patients and Methods: Thirty seven patients with unresectable (n = 34) or i ncompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine wa s administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m( 2) an days 1, 8, and 15 of a 28-day cycle. Radiation therapy was initiated on day 1 and directed at the primary tumor alone, without prophylactic noda l coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Esca lation was achieved by increasing the fraction size in increments of 0.2 Gy , keeping the duration of radiation constant at 3 weeks. A second cycle of gemcitabine alone was intended after a 1-week rest. Results: Two of six assessable patients experienced dose-limiting toxicity at the final planned dose level of the trial (42 Gy in 2.8-Gy fractions), o ne with grade 4 vomiting and one with gastric/duodenal ulceration. Two addi tional patients at this dose level experienced late gastrointestinal toxici ty that required surgical management. Conclusion: The final dose investigated (42 Gy) is not recommended for furt her study considering the occurrence of both acute and late toxicity. Howev er, a phase II trial of this novel gemcitabine-based chemoradiatherapy appr oach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on t he basis of tolerance, patterns of failure, and survival data. (C) 2001 by American Society of Clinical Oncology.