title: Phase II trial of dacarbazine and thalidomide for the treatment of metastatic melanoma.
abstract: OBJECTIVE
  This phase II study evaluated the efficacy and tolerability of dacarbazine in combination with thalidomide in metastatic melanoma patients.
  
  
  METHODS
  Chemotherapy-naïve patients with histologically confirmed, measurable metastatic melanoma with no evidence of brain metastases and adequate hematologic and organ function received dacarbazine (1,000 mg/m(2) i.v. every 3 weeks) and thalidomide (starting dose of 200 mg/day orally at night, escalated every 3 weeks) as tolerated. The primary endpoint was objective tumor response, evaluated after every 3 cycles of treatment. Fifteen patients, age range 29-77 years, were accrued for this study. All had stage IV disease (1 M1a, 5 M1b, 9 M1c). Nine patients had had no prior adjuvant therapy, 6 had received prior immunotherapy. The median number of cycles was 5 (range 1-18), with 8 patients receiving >or=3 cycles. The median thalidomide dose administered was 200 mg/day with a maximum tolerated dose of 400 mg/day.
  
  
  RESULTS
  Of the 13 patients evaluable for response, 1 patient had a partial response, 3 patients had stable disease and 9 patients had progressive disease. No complete responses were seen. Two patients were not evaluable for response: 1 withdrew due to toxicity and 1 died of unrelated causes. Grade III neutropenia, thrombocytopenia and nausea were attributed to dacarbazine. Grade III/IV constipation, peripheral neuropathy, fatigue, edema and rash were attributed to thalidomide.
  
  
  CONCLUSIONS
  The addition of thalidomide to dacarbazine in metastatic melanoma yielded activity insufficient to proceed with additional trials of this combination. Thalidomide dose escalation beyond 200 mg/day was limited by unacceptable toxicity. Therefore, this combination does not warrant further investigation.
authors.affiliation: Division of Medical Oncology, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. patrick.ott@nyumc.org
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.forename: Jason L
authors.initials: JL
authors.lastname: Chang
authors.forename: Ruth
authors.initials: R
authors.lastname: Oratz
authors.forename: Amanda
authors.initials: A
authors.lastname: Jones
authors.forename: Kathleen
authors.initials: K
authors.lastname: Farrell
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D013792:Thalidomide; D003606:Dacarbazine