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Phase I Trial of Radiation Dose Escalation With Concurrent Weekly Full-Dose Gemcitabine in Patients With Advanced Pancreatic Cancer

From the Department of Radiation Oncology, University of Michigan, Ann Arbor; and William Beaumont Hospital, Royal Oak, MI.

Address reprint requests to Cornelius J. McGinn, MD, Department of Radiation Oncology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0010; email: mcginn{at}umich.edu

PURPOSE: The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer.

PATIENTS AND METHODS: Thirty seven patients with unresectable (n = 34) or incompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine was administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m² on 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 nodal coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation 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), one with grade 4 vomiting and one with gastric/duodenal ulceration. Two additional patients at this dose level experienced late gastrointestinal toxicity that required surgical management.

CONCLUSION: The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiotherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data.

Presented in part at the Forty-Second Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Boston, MA, October 21-25, 2000, and the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999.

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