title: Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.
abstract: BACKGROUND
  In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen.
  
  
  METHODS
  From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression.
  
  
  RESULTS
  A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy.
  
  
  CONCLUSIONS
  The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.
authors.affiliation: Division of Medical Oncology A, National Tumor Institute, Naples, Italy. pasciert@tin.it
authors.forename: A
authors.initials: A
authors.lastname: Daponte
authors.forename: P A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: A
authors.initials: A
authors.lastname: Gravina
authors.forename: M T
authors.initials: MT
authors.lastname: Melucci
authors.forename: G
authors.initials: G
authors.lastname: Palmieri
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: R
authors.initials: R
authors.lastname: Cellerino
authors.forename: M
authors.initials: M
authors.lastname: DeLena
authors.forename: G
authors.initials: G
authors.lastname: Marini
authors.forename: G
authors.initials: G
authors.lastname: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D051929:CD146 Antigen; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics; D009325:Nausea / Q000139:chemically induced; D009363:Neoplasm Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D009503:Neutropenia / Q000139:chemically induced; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D051929:CD146 Antigen; D016898:Interferon-alpha; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019006:Neural Cell Adhesion Molecules; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D003606:Dacarbazine; D014442:Monophenol Monooxygenase; C054368:fotemustine; D002945:Cisplatin