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.