title: Phase II multicentre study of temozolomide in combination with interferon alpha-2b in metastatic malignant melanoma.
abstract: OBJECTIVE
  Temozolomide is a novel oral alkylating agent, active against metastatic melanoma. Combinations of chemotherapy and biological response modifiers have been associated with increased antitumour activity. A multicentre phase II study was performed to assess the activity and toxicity of temozolomide in combination with interferon alpha-2b.
  
  
  METHODS
  Eligible patients had histologically confirmed metastatic melanoma. Previously untreated patients received temozolomide administered orally at a dose of 150 mg/m/day for 5 days every 4 weeks, in combination with interferon given continuously subcutaneously twice a week at a dose of 10 MU/m. Treatment continued until disease progression or for a maximum of 12 months.
  
  
  RESULTS
  From June 1999 to August 2002, 27 eligible patients were included in the study at six centres. Median age was 59 (28-77) years; 17 male and 10 female patients were recruited; the median Karnofsky performance score was 90 (70-100); three patients had received prior adjuvant interferon; the majority of patients had fewer than three involved sites. A total of 96 cycles were administered; there were one complete response, four partial response and five stable disease (overall response rate: 18.5%, 95% confidence interval: 6.3-38.1). All responses were seen in patients with exclusively lymph node and pulmonary disease [M1a (one patient); M1b (four patients)]. The median response duration was 6.9 months. One patient remains in complete remission at 4 years. The median time to progression and the median survival were 1.87 and 9.5 months, respectively. Haematological toxicity was neutropenia G-IV: 1, G-III: 4, thrombocytopenia G-III: 2, and anaemia G-III: 2. Predominant non-haematological toxicity was hepatotoxicity G-III: 4. Other toxicities were mild or moderate. Dose reduction was required for nine cycles of interferon, one of temozolomide and two of both drugs.
  
  
  CONCLUSIONS
  Temozolomide in combination with interferon is a well-tolerated palliative regimen that has moderate activity against metastatic melanoma. Further evaluation of this regimen in comparative studies or in combination with other drugs is warranted.
authors.affiliation: Department of Clinical Research Unit, Hospital Durán i Reynals IDIBELL, Barcelona, Spain. mgarciamartin@iconcologia.net
authors.forename: Margarita
authors.initials: M
authors.lastname: García
authors.forename: Xavier García
authors.initials: XG
authors.lastname: del Muro
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tres
authors.forename: Carmen
authors.initials: C
authors.lastname: Crespo
authors.forename: Manuel
authors.initials: M
authors.lastname: Valladares
authors.forename: Juan José
authors.initials: JJ
authors.lastname: López
authors.forename: Julio
authors.initials: J
authors.lastname: Rifà
authors.forename: Xavier
authors.initials: X
authors.lastname: Pérez
authors.forename: Elena
authors.initials: E
authors.lastname: Filipovich
authors.forename: Josep Ramón
authors.initials: JR
authors.lastname: Germà-Lluch
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003606:Dacarbazine; D000077204:Temozolomide