A pilot study of chronomodulated infusional 5-fluorouracil chemoradiation for pancreatic cancer

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 spec ific evaluation of acute and late morbidity, patterns of disease progressio n, and survival. Patients and methods: Twenty-three patients with adenocarcinoma of the panc reas were treated with 5-FU CIC between January 1997 and September 1999. Th e median age was 64, and there were 9 males and 14 females. Six patients we re considered unresectable and seventeen others were treated post-operative ly. The median external beam irradiation dose was 50.4 Gy. 5-FU infusion wa s given five days per week (300 mg/m(2)/d) and the median total dose was 8. 4 g/m(2). The chronomodulated 5-FU infusion consists of a low basal infusio n rate for 16 hours followed by an eight-hour escalating-deescalating infus ion 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 seve nteen patients treated postoperatively have been controlled locally, and se ven 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. T he 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 les s severe than that reported with flat infusional or bolus 5-FU based chemor adiation used for adjuvant post-operative therapy for pancreatic cancer. Th is 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.