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A phase I trial of 5‐fluorouracil, folinic acid, and alpha‐2a‐interferon in patients with metastatic colorectal carcinoma
Author(s) -
Bukowski Ronald M.,
Inoshita Go,
Yalavarthi Prasad,
Murthy Siva,
Gibson Vicki,
Budd G. Thomas,
Sergi James S.,
Bauer Laurie,
Prestifilippo Judith
Publication year - 1992
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(19920215)69:4<889::aid-cncr2820690409>3.0.co;2-r
Subject(s) - medicine , folinic acid , mucositis , fluorouracil , alpha interferon , neutropenia , gastroenterology , interferon alfa , colorectal cancer , chemotherapy , dosing , cancer , interferon , immunotherapy , immunology
The mechanisms of biochemical modulation of 5‐fluorouracil (5‐FU) cytotoxicity by folinic acid (FA) have been elucidated, and the clinical use of this combination has improved response rates and survival in patients with metastatic colorectal cancer. Recently, Phase II trials also showed potential synergism between alpha‐2a‐inter‐feron (rHuIFN‐α2a) and 5‐FU. Therefore, a Phase I trial of these three agents 5‐FU, FA, and rHuIFN‐α2a was conducted in patients with metastatic colorectal cancer. The drugs were given over 5 days, with dose escalation of either rHuIFN‐α2a or 5‐FU. Fifty‐five eligible patients were treated at eight dosing levels. The maximal tolerated dose (MTD) was as follows: 5‐FU 430 mg/m 2 /d intravenously (IV) on days 1 to 5, FA 200 mg/m 2 IV on days 1 to 5, and rHuIFN‐α2a 4.0 × 10 6 U/m 2 /d subcutaneously on days 1 to 5. The dose‐limiting toxicities were mucositis and neutropenia. Objective responses were seen at most dosing levels, and overall 15 of 55 patients (27%; 95% confidence interval, 16% to 41%) responded (median duration, 6.5 months). A Phase II trial using the MTD is ongoing. Cancer 1992; 69:889–892.