Phase I study of WR-2721 and carboplatin.
Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.
Department of Hematology/Medical Oncology, Cleveland Clinic, Ohio 44195.
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GT
Budd
R
R
Ganapathi
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L
Bauer
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S
Murthy
D
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Adelstein
J
J
Weick
V
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Gibson
D
D
McLain
J
J
Sergi
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Bukowski
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D010984:Platinum / Q000097:blood; D013921:Thrombocytopenia / Q000139:chemically induced
D010984:Platinum; D016190:Carboplatin; D004999:Amifostine