title: Phase II trial of tirapazamine combined with cisplatin in chemotherapy of advanced malignant melanoma.
abstract: OBJECTIVE
  A phase II study was undertaken to determine the efficacy of tirapazamine (TPZ) combined with cisplatin (cDDP) in patients with metastatic melanoma.
  
  
  METHODS
  Between June 1994 and November 1995, 48 patients with metastatic melanoma were treated with TPZ (260 mg/m2, administered intravenously over two hours) followed in one-hour by cDDP (75 mg/m2 over one hour) every 21 days. Sixteen patients had received prior chemotherapy, and 13 of these had failed to respond to prior cDDP. None of the patients had symptomatic brain metastasis.
  
  
  RESULTS
  Nine patients had partial responses, with an overall response rate of 19% (95% confidence interval (95% CI) of 9%-33%). The median duration of response was six months. None of the responders had received prior chemotherapy. Responses were seen in 8 (33%, confidence interval of 16%-55%) of 24 patients with primary cutaneous melanoma who had received no prior chemotherapy and in the only patient with previously untreated conjunctival melanoma. There were no responders among the seven patients with choroidal melanoma and 16 patients with previously treated cutaneous melanoma. Two patients with partial responses were rendered free of gross disease surgically three months after completing eight courses of TPZ-cDDP; they remain free of tumor recurrence. Responses were seen in lymph nodes (27%), lung (26%), skin (20%), adrenal gland (20%), soft tissues (17%) and liver (17%). Common toxicities included muscle cramps, fatigue, gastrointestinal effects and peripheral neuropathy. Fatigue, nausea, vomiting, anorexia, and muscle cramps were grade 3 or 4 in less than 10% of the courses. Neutropenia and thrombocytopenia were rare.
  
  
  CONCLUSIONS
  The TPZ-cDDP combination has definite activity against chemotherapy-naïve patients with cutaneous melanoma and warrant further studies in combination with other cytotoxic agents.
authors.affiliation: Department of Melanoma/Sarcoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, USA.
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: S
authors.initials: S
authors.lastname: Coates
authors.forename: T
authors.initials: T
authors.lastname: Simmons
authors.forename: J
authors.initials: J
authors.lastname: Neefe
authors.forename: R
authors.initials: R
authors.lastname: von Roemeling
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage
chemical_list: D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin