title: High-dose cisplatin plus WR-2721 in a split course in metastatic malignant melanoma. A phase II study.
abstract: Nine patients with metastatic malignant melanoma were entered onto a phase II trial consisting of WR-2721, 740 mg/m2 i.v. over 15 min, followed 15 min after completion by cisplatin, 100 mg/m2 i.v. over 30 min in 250 cc of 3% saline, on days 1 and 8 every 4 weeks. Six patients received two full courses of chemotherapy and were considered evaluable for response. No patients obtained a response. Toxicity, assessed according to the National Cancer Institute Common Toxicity Criteria, was acceptable and usually transient. However, fatigue, which manifested as a decrease in performance status, was significant in six of eight patients in whom this side effect could be evaluated. This subjective toxicity was most likely due to the high-dose cisplatin therapy. The lack of response in six fully evaluable patients allowed us to conclude with greater than 95% confidence that the combination of high-dose cisplatin and WR-2721 in a split-course day 1 and 8 schedule has a true response rate of less than 40%. In view of the relatively high subjective toxicity observed in our study and the more encouraging results observed by other groups using a different dose schedule of WR-2721 plus cisplatin, we do not recommend the use of high-dose cisplatin plus WR-2721 as employed in this trial.
authors.affiliation: Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: A C
authors.initials: AC
authors.lastname: Buzaid
authors.forename: J
authors.initials: J
authors.lastname: Murren
authors.forename: H J
authors.initials: HJ
authors.lastname: Durivage
mesh_terms: D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006311:Hearing Disorders / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy*; D014839:Vomiting / Q000139:chemically induced
chemical_list: D003404:Creatinine; D004999:Amifostine; D002945:Cisplatin