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A phase I trial of cisplatin in hypertonic saline and escalating doses of 5‐fluorouracil by continuous intravenous infusion in patients with advanced malignancies
Author(s) -
Saltz Leonard,
Kelsen David
Publication year - 1990
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(19901015)66:8<1688::aid-cncr2820660806>3.0.co;2-k
Subject(s) - medicine , mucositis , leukopenia , hypertonic saline , dose , fluorouracil , cisplatin , chemotherapy , gastroenterology , nephrotoxicity , carboplatin , toxicity , anesthesia
Thirty‐four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high‐dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5‐fluorouracil (5‐FU). Five treatment levels of 5‐FU, ranging from 500 to 900 mg/m 2 /day for 5 days, were studied. Leukopenia, thrombocytopenia, and oral mucositis were the dose‐limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles. Diarrhea was not dose‐limiting. Two complete responses (one non‐small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m 2 /day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5‐day 5‐FU infusion was found to be 900 mg/m 2 /day. The recommended dosages for Phase II trials are 35 mg/m 2 /day CDDP and 800 mg/m 2 /day 5‐FU for 5 consecutive days. Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies.