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Published on: May 12, 2023
A pilot study of chronomodulated infusional 5-fluorouracil chemoradiation for pancreatic cancer
D R Penberthy1, T A Rich, C H Shelton
1Department of Radiation Oncology, University of Virginia Health Sciences Center, Charlottesville 22901, USA.
Background:
Dose limiting acute toxicity from chemoradiation for pancreatic cancer occurs in 15% -20% of patients treated with post-operative adjuvant therapy. Reported here is a pilot study using chronomodulated infusional 5-fluorouracil (5-FU) chemoradiation (CIC) for pancreatic cancer, a treatment designed to reduce normal tissue toxicity and maintain efficacy, with specific evaluation of acute and late morbidity, patterns of disease progression, and survival.
Patients And Methods:
Twenty-three patients with adenocarcinoma of the pancreas were treated with 5-FU CIC between January 1997 and September 1999. The median age was 64, and there were 9 males and 14 females. Six patients were considered unresectable and seventeen others were treated post-operatively. The median external beam irradiation dose was 50.4 Gy. 5-FU infusion was given five days per week (300 mg/m2/d) and the median total dose was 8.4 g/m2. The chronomodulated 5-FU infusion consists of a low basal infusion rate for 16 hours followed by an eight-hour escalating-deescalating infusion peaking at 10 p.m. All patients were followed from the time of initial diagnosis until last follow-up or death; the median follow-up was 16 months.
Results:
No RTOG grade 3 or 4 hematologic toxicity occurred. Twelve of seventeen patients treated postoperatively have been controlled locally, and seven patients have no evidence of disease. The median survival is 28 months and one-year actuarial survival is 88% in the group of resected patients. The 6 patients treated for unresectable disease have a median survival of 13 months.
Conclusions:
Acute toxicity of 5-FU CIC appears to be less frequent and less severe than that reported with flat infusional or bolus 5-FU based chemoradiation used for adjuvant post-operative therapy for pancreatic cancer. This method may warrant further examination, as it may be attractive for the elderly or those who cannot tolerate the toxicity associated with standard post-operative treatment protocols.