Cis-Dichlorodiammine platinum and adriamycin therapy for advanced gynecological and genitourinary neoplasms.
Cis-Dichlorodiammine platinum (DDP) 75 mg/m2 on days 1 and 8 and Adriamycin (ADR) 60 mg/m2 on day 1 were used in 31 patients with advanced gynecological and genitourinary neoplasms. The DDP was given by 6 hours intravenous infusion with 2 liters of 5% Dextrose and 0.5 normal saline using Mannitol and/or furosemide diuresis. Courses were repeated every 21 to 28 days. Responses were seen in 7 of 8 patients with germinal cell neoplasms (5 complete, 2 partial) with a median duration of eight months. A partial response was obtained in 3 of 7 patients with bladder carcinoma with a median duration of three months. There were four partial responses obtained in 9 patients with ovarian carcinoma with a median duration of five months. Toxicities included nausea and vomiting in all 31 patients, nephrotoxicity (serum creatinine > 2 g/100 ml) in patients, tinnitus and/or high frequency hearing loss in 10 patients, and neurotoxicity (peripheral neuropathy, normal pressure hydrocephalus, papilledema) in 8 patients. Severe leukopenia (WBC < 2000/cu mm) and thrombocytopenia (< 100,000/cu mm) occurred in 25% and 45% of evaluable courses, respectively and necessitated dosage reduction in all and delay of therapy in some patients. Peak plasma Pt levels were 2.61 +/- .18 microgram/cc on day 1 and 3.52 +/- .39 microgram/cc on day 8 with a longer terminal half-life on day 8 (252 hours) compared to day 1 (156 hours). Peak plasma ADR levels ranged from .53 to 1.67 N moles/cc with an average terminal half-life of 22.8 hours. This agrees with values of ADR when given alone. This dose and schedule of DDP-ADR is active against advanced gynecological and genitourinary neoplasms, but the amount of toxicity seen indicates that modifications will have to be made.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001791:Blood Platelet Disorders / Q000139:chemically induced; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D034381:Hearing Loss / Q000139:chemically induced; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D007700:Kinetics; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009422:Nervous System Diseases / Q000139:chemically induced; D014012:Tinnitus / Q000139:chemically induced; D014565:Urogenital Neoplasms / Q000188:drug therapy*
D005665:Furosemide; D004317:Doxorubicin; D002945:Cisplatin