Phase II study of 5-fluorouracil and folinic acid in the treatment of patients with advanced gastric cancer. A Southwest Oncology Group study.
BACKGROUND
The biochemical modulation of 5-fluorouracil (5-FU) by the reduced folate folinic acid (FA) in the treatment of patients with advanced gastric cancer was examined.


METHODS
The Southwest Oncology Group performed parallel randomized Phase II trials of two schedules of 5-FU and FA in 80 patients with advanced gastric cancer. Of 76 analyzable patients, 36 were randomized to receive bolus FA (200 mg/m2, days 1-4) along with continuous infusion 5-FU (1000 mg/m2, days 1-4) and 40 were randomized to receive bolus FA (200 mg/m2, days 1-5) before the bolus 5-FU (375 mg/m2, days 1-5).


RESULTS
There were three (8%) partial responses (95% confidence interval [CI] 2%-22%) on the continuous infusion arm. The bolus arm had two (5%) complete responses and six (15%) partial responses for an overall response rate of 20% (95% CI 9%-36%). The median duration of response was 4.6 months for the infusion patients and 16.6 months for the bolus patients. Survival was poor, with median survival of 5 months on both regimens. Gastrointestinal toxicity was substantial, with Grade 3 mucositis observed in 36% of patients on the continuous infusion regimen versus only 10% of patients on the bolus regimen. Grade 3 or higher hematologic toxicity occurred more often in the bolus arm than in the continuous infusion arm (28% vs. 14%, respectively). Two toxic deaths occurred, one related to sepsis the other secondary to coronary insufficiency.


CONCLUSIONS
Biochemical modulation of 5-FU by FA using the dose and schedules tested has only modest activity in the treatment of advanced gastric cancer.
Berenberg
J L
JL
Cancer Research Center of Hawaii, Honolulu, USA.
Tangen
C
C
Macdonald
J S
JS
Hutchins
L F
LF
Natale
R B
RB
Oishi
N
N
Guy
J T
JT
Fleming
T R
TR
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000931:Antidotes / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil