Phase I study of hyperfractionated radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer.
OBJECTIVE
This study investigated the maximum-tolerated dose of hyperfractionated radiation therapy with protracted 5-fluorouracil (5-FU) infusion in patients with locally advanced, unresectable pancreatic cancer.


METHODS
Five cohorts of patients were scheduled to receive escalating doses of hyperfractionated radiation therapy (range, 45.6-64.8 Gy). All patients received two fractions of 1.2 Gy each (separated by 6 h) per day for 5 days a week, and received protracted 5-FU infusion (200 mg/m2/day) during the radiation course. The maximum-tolerated dose was defined as one dose level below the dose at which more than one third of 3-6 patients experienced dose-limiting toxicity.


RESULTS
Twenty-nine patients were enrolled in this study. The most common toxicities were nausea/vomiting and anorexia. Although 1 patient developed bleeding from a gastric ulcer 3 months after the completion of chemoradiotherapy, the maximum-tolerated dose was not reached even at the highest dose level (level 5, 64.8 Gy). The median survival time was 12.2 months and the 1-year survival rate was 55.0%.


CONCLUSIONS
The toxicity associated with our regimen was tolerable up to dose level 5 (64.8 Gy). We are currently conducting a phase II study of this hyperfractionated radiation therapy with protracted 5-FU infusion at a dose of 64.8 Gy.
Ueno
Hideki
H
Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. hiueno@ncc.go.jp
Okusaka
Takuji
T
Ikeda
Masafumi
M
Tokuuye
Koich
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil