A phase II trial of alpha-interferon and 5-fluorouracil in patients with advanced carcinoid and islet cell tumors.

5-Fluorouracil (5-FU) has shown modest single-agent activity in patients with carcinoid or islet cell tumors. Alpha interferon (alpha-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 alpha-IFN and 5-FU has demonstrated enhanced activity in several gastrointestinal malignancies.
Twenty-one patients with advanced neuro-endocrine tumors (14 with carcinoid tumors, 7 with islet cell carcinomas) were treated with alpha-IFN and 5-FU in a Phase II study. 5-Fluorouracil was administered by intravenous bolus injection at an initial dose of 400 mg/m2/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/m2. Alpha interferon administration was begun on Day 1 of 5-FU at a daily dose of 3 x 10(6) U subcutaneously and continued for the duration of the trial.
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 partial 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 alpha-IFN, 14 of 21 patients required a dose reduction in the alpha-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.
These results suggest that the combination of 5-FU and alpha-IFN does not have any clear superiority over the individual agents alone; 5-FU appears to reduce patient tolerance of alpha-IFN when given on a daily schedule. Further investigations are needed to identify active agents in the treatment of neuroendocrine malignancies.
AuthorsL Saltz, N Kemeny, G Schwartz, D Kelsen
JournalCancer (Cancer) Vol. 74 Issue 3 Pg. 958-61 (Aug 1 1994) ISSN: 0008-543X [Print] UNITED STATES
PMID8039124 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Interferon-alpha
  • Fluorouracil
  • Adenoma, Islet Cell (therapy)
  • Adult
  • Aged
  • Carcinoid Tumor (therapy)
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluorouracil (administration & dosage, adverse effects)
  • Humans
  • Interferon-alpha (administration & dosage, adverse effects)
  • Male
  • Middle Aged
  • Pancreatic Neoplasms (therapy)
  • Treatment Outcome

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