A phase I study of combined radiation therapy with 5-fluorouracil and low dose folinic acid in patients with locally advanced pancreatic or biliary carcinoma.
OBJECTIVE
To evaluate the toxicities of a Phase I study of radiation therapy with concurrent 5-fluorouracil (5FU) and low dose folinic acid in patients with locally advanced pancreatic or biliary carcinoma.


METHODS
Twenty-seven patients with locally advanced carcinoma of the pancreas (n = 19), bile duct (n = 7), and gall bladder (n = 1) were entered into a Phase I study of combined radiation therapy, 5FU, and folinic acid. Radiation was given as a split course of 40 Gy in 20 daily fractions with a gap of 2 weeks after 20 Gy. 5-Fluorouracil, 300 to 375 mg/m2/day and folinic acid, 20 mg/m2/day were given as an i.v. bolus daily for 5 days beginning on day 1 and again on day 29.


RESULTS
Eight patients developed Grade 3 or 4 toxicities (National Cancer Institute common toxicity criteria) including nausea and vomiting (n = 4), oral mucositis (n = 4), myelosuppression (n = 2), infection (n = 2), and diarrhea (n = 1). Four patients did not complete the planned protocol due to treatment toxicities. There were two treatment deaths secondary to septic neutropenia. Treatment toxicity appeared to be related to age (> 70), performance status (ECOG = 2), and 5FU dose (> 350 mg/m2/day).


CONCLUSIONS
This protocol is poorly tolerated by elderly patients or those with poor performance status, and 350 mg/m2/day is our recommended dose for 5FU as given in this protocol.
Hsue
V
V
Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
Wong
C S
CS
Moore
M
M
Erlichman
C
C
Cummings
B J
BJ
MacLeod
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000931:Antidotes / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D016019:Survival Analysis
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil