title: Etoposide admixed with cisplatin. Phase I clinical investigation of 72-hour infusion.
abstract: The compatibility of etoposide (VP-16-213) and cisplatin (CDDP) in an admixture solution was established by High Pressure Liquid Chromatography (HPLC) studies in vitro at room temperature. A Phase I dual-dose escalation study of the admixture was subsequently carried out utilizing a 24-hour continuous infusion schedule administered for 3 consecutive days and repeated at 3 to 4 week intervals. Twenty-seven patients received a total of 42 treatment courses. The daily dose rates for VP-16-213 were 50, 75, and 100 mg/m2/day. Cisplatin was delivered at 20, 30, and 40 mg/m2/day for each dose level of VP-16-213. Dose-rate limiting toxicity was observed first at the VP-16 dose of 50 mg/m2/day and CDDP at 30 mg/m2/day. At 100 mg/m2/day for VP-16-213, six of 17 courses were associated with life-threatening leukopenia and four of six patients died with sepsis. All but one of the patients developing severe or life-threatening leukopenia had associated acute renal failure with serum creatinine levels greater than 2 mg/dl. The optimal dose rate of delivery for VP-16 and CDDP administered as a 72-hour infusion admixture is 75 mg/m2/day and 30 mg/m2/day, respectively.
authors.affiliation: Cancer Center, Boston, MA 02120.
authors.forename: J
authors.initials: J
authors.lastname: Lokich
authors.forename: N
authors.initials: N
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Bern
authors.forename: S
authors.initials: S
authors.lastname: Wallach
authors.forename: C
authors.initials: C
authors.lastname: Moore
authors.forename: D
authors.initials: D
authors.lastname: Williams
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D004338:Drug Combinations; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D012074:Remission Induction
chemical_list: D004338:Drug Combinations; D005047:Etoposide; D003404:Creatinine; D002945:Cisplatin