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A phase II trial of alpha‐interferon and 5‐fluorouracil in patients with advanced carcinoid and islet cell tumors
Author(s) -
Saltz Leonard,
Kemeny Nancy,
Schwartz Gary,
Kelsen David
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940801)74:3<958::aid-cncr2820740326>3.0.co;2-x
Subject(s) - medicine , alpha interferon , fluorouracil , interferon alfa , gastroenterology , bolus (digestion) , carcinoid tumors , islet , chemotherapy , carcinoid syndrome , carcinoid tumour , neuroendocrine tumors , interferon , immunology , insulin
Abstract Background . 5‐Fluorouracil (5‐FU) has shown modest single‐agent activity in patients with carcinoid or islet cell tumors. Alpha interferon (α‐IFN) has also shown modest single agent activity in these diseases, although biologic responses have been far more prevalent than have objective tumor regressions. The combination of a‐IFN and 5‐FU has demonstrated enhanced activity in several gastrointestinal malignancies. Methods . Twenty‐one patients with advanced neuroendocrine tumors (14 with carcinoid tumors, 7 with islet cell carcinomas) were treated with a‐IFN and 5‐FU in a Phase II study. 5‐Fluorouracil was administered by intravenous bolus injection at an initial dose of 400 mg/m 2 / day for 5 consecutive days. After a 1‐week break, 5‐FU then was administered weekly by intravenous bolus at a dose of 750 mg/m 2 . Alpha interferon administration was begun on Day 1 of 5‐FU at a daily dose of 3 × 10 6 U subcutaneously and continued for the duration of the trial. Results . Of the 14 carcinoid patients with carcinoid tumors, 1 experienced a partial response (7%; 95% confidence interval [CI] 0‐20%) that lasted for 6 months. Eight of the patients with carcinoid tumors achieved stable disease for a median of 6 months (range, 2‐10 months). One of the patients with islet cell tumors (14%; 95% CI 0‐39%) achieved a patrtial response that persisted after 8 months; 4 patients with islet cell tumors had stable disease for a median of 13 months (range, 4‐27+ months). Even at this relatively low dose of a‐IFN, 14 of 21 patients required a dose reduction in the a‐IFN (13 for fatigue, 1 for ataxia). Three patients experienced myelosuppression of greater than Grade 3, and three patients had diarrhea of greater than Grade 3. One patient experienced dose‐limiting hand‐foot syndrome. Conclusions . These results suggest that the combination of 5‐FU and a‐IFN does not have any clear superiority over the individual agents alone; 5‐FU appears to reduce patient tolerance of a‐IFN when given on a daily schedule. Further investigations are needed to identify active agents in the treatment of neuroendocrine malignancies.