title: Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in metastatic malignant melanoma.
abstract: The results of cytostatic therapy in metastatic melanoma are very disappointing. In phase II studies with high-dose cisplatin regimens, a remarkably high response rate was observed. In a phase I study with a short course of weekly cisplatin, combined with oral etoposide, we were able to reach, in most patients, a cisplatin dose intensity of 60 mg/m2/week. We performed a phase II study with this schedule in metastatic malignant melanoma. 15 consecutive patients were entered in the study. Treatment consisted of cisplatin 70 mg/m2 on days 1, 8, 15 and days 29, 36, 43 combined with oral etoposide 50 mg daily, days 1-15 and days 29-43. Patients with a response or stable disease continued treatment with oral etoposide 50 mg/m2 daily, days 1-21 every 4 weeks. All patients were evaluable for response and toxicity. The majority of the patients received six cycles of cisplatin with the planned cisplatin dose intensity of 60 mg/m2/week. A partial response was observed in 2 patients (13%; 95% confidence interval (CI) 2-44%) of, respectively, 22 and 12 weeks; stable disease was observed in 6 patients. Toxicity consisted mainly of alopecia and bone marrow suppression. 4 patients had tinnitus, one patient had neurotoxicity grade 1. The regimen studied has only limited activity in metastatic melanoma in spite of the high-dose intensity of cisplatin reached with this schedule.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute/Daniel den Hoed Kliniek, The Netherlands.
authors.forename: A S
authors.initials: AS
authors.lastname: Planting
authors.forename: M E
authors.initials: ME
authors.lastname: van der Burg
authors.forename: S H
authors.initials: SH
authors.lastname: Goey
authors.forename: J H
authors.initials: JH
authors.lastname: Schellens
authors.forename: C
authors.initials: C
authors.lastname: Vecht
authors.forename: M
authors.initials: M
authors.lastname: de Boer-Dennert
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000473:pathology*
chemical_list: D005047:Etoposide; D002945:Cisplatin