Clinical trials of WR-2721 and cis-platinum.
WR-2721 is an aminothiol compound; in the animal model it protects against the nephrotoxicity, neurotoxicity, and hematologic toxicity of cis-platinum. We initiated Phase I trials of WR-2721 and cis-platinum to determine toxicity when WR-2721 was given prior to escalating doses of cis-platinum. With mannitol diuresis and WR-2721, transient nephrotoxicity occurred in 9 of 30 (27%) patients treated with cis-platinum 150 mg/m2 and 7% of patients given with cis-platinum 120 mg/m2. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies occurred in 26% of patients courses following a mean cumulative cis-platinum dose of 725 mg/m2. Objective partial responses were observed in 53 of 118 (45%) patients with measurable disease. Antitumor responses were observed in 25 of 53 patients with metastatic melanoma, 12 of 22 patients with locally recurrent or metastatic head and neck cancer, and 7 of 13 patients with metastatic breast cancer refractory to conventional chemotherapy. Controlled studies of WR-2721 and cis-platinum will be performed in the Eastern Cooperative Oncology Group in these disease sites to better define the activity of this regimen and its toxicity.
Glover
D
D
Department of Radiation Therapy, University of Pennsylvania, Philadelphia 19104.
Grabelsky
S
S
Fox
K
K
Weiler
C
C
Cannon
L
L
Glick
J
J
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004231:Diuresis / Q000187:drug effects; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*
D009946:Organothiophosphorus Compounds; D008353:Mannitol; D004999:Amifostine; D002945:Cisplatin