title: Phase II trial of escalated dose of tirapazamine combined with cisplatin in advanced malignant melanoma.
abstract: A phase II study was undertaken to determine the efficacy of tirapazamine combined with cisplatin in patients with metastatic melanoma between April 1996 and April 1997. Tirapazamine 390 mg/m2, administered i.v. over 2 h, followed in 1 h by cisplatin 75 mg/m2 over 1 h, were used every 21 days to treat chemotherapy-naive patients with metastatic melanoma. Objective tumor measurements were used to assess efficacy of the regimen. NCI common toxicity criteria were used to grade toxicities. Forty-eight patients with metastatic melanoma of cutaneous or mucosal origin, none with symptomatic brain metastasis, were treated. Nine patients had a partial response, with an overall response rate of 20% (95% confidence interval: 9-33%). The median duration of response was 6 months. Grade 3 nausea, vomiting, anorexia, muscle cramps and fatigue occurred in fewer than 10% of patients. Neutropenia and thrombocytopenia were rare. This outpatient single-day administered tirapazamine-cisplatin regimen has definite activity in chemotherapy-naive patients with metastatic melanoma. Further studies in combination with other agents active against this disease are warranted.
authors.affiliation: Department of Melanoma/Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, USA. abedikia@notes.mdacc.tmc.edu
authors.forename: A Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: S S
authors.initials: SS
authors.lastname: Legha
authors.forename: O
authors.initials: O
authors.lastname: Eton
authors.forename: A C
authors.initials: AC
authors.lastname: Buzaid
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: C
authors.initials: C
authors.lastname: Plager
authors.forename: S
authors.initials: S
authors.lastname: McIntyre
authors.forename: J
authors.initials: J
authors.lastname: Viallet
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D013997:Time Factors; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin