title: Interferon-alpha and chemohormonal therapy for patients with advanced melanoma: final results of a phase I-II study of the Cancer Biotherapy Research Group and the Mid-Atlantic Oncology Program.
abstract: BACKGROUND
  The treatment of metastatic melanoma remains unsatisfactory despite encouraging results with biotherapy and combination chemotherapy. Combining these two modalities may improve outcomes for such patients.
  
  
  METHODS
  Patients who were eligible for this study had metastatic melanoma and were in good medical condition. The following regimen was used: dacarbazine 220 mg/m2 and cisplatin 25 mg/m2 administered intravenously (i.v.) daily x 3 days every 3 weeks, carmustine 150 mg/m2 i.v. every 6 weeks, tamoxifen 10 mg administered orally twice a day, and interferon-alpha2b 3.0 thousandths of an International Unit (mIU)/m2 administered subcutaneously on Days 1, 3, and 5 of each week a patient was on study. Patients were analyzed for toxicity, tumor response, and survival. Because of severe toxicity, partway through the trial the regimen was modified as follows: dacarbazine and cisplatin were given at the same dose every 4 weeks, and carmustine was reduced to 100 mg/m2 every 8 weeks.
  
  
  RESULTS
  Forty-two patients with a median age of 61 years were enrolled. Twenty had liver metastases and 18 had lung metastases. Forty patients were evaluable for toxicity, 17 at the original dose and 23 at the new dose; of these, 35 were evaluable for response. Hematologic toxicity was severe at the original dose: 10 patients had a nadir < 500/microL, 10 had platelets < 25,000/microL, and 2 discontinued treatment because of toxicity. At the reduced dose, 5 had a nadir absolute neutrophil count < 500, and 10 had platelets < 25,000. Of the 35 patients evaluable for response, there were 10 partial responses (29%) and 2 minimal responses. Median duration of disease control was 4 months. Median survival was 8.9 months. One partial and one minimal responder were removed from the study because they experienced toxicity while still responding.
  
  
  CONCLUSIONS
  The addition of interferon-alpha to this chemohormonal therapy regimen greatly increased toxicity without improving the response rate or survival for patients with metastatic melanoma.
authors.affiliation: Maryview Medical Center, Portsmouth Virginia, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Stark
authors.forename: R O
authors.initials: RO
authors.lastname: Dillman
authors.forename: R
authors.initials: R
authors.lastname: Schulof
authors.forename: M C
authors.initials: MC
authors.lastname: Wiemann
authors.forename: N M
authors.initials: NM
authors.lastname: Barth
authors.forename: P J
authors.initials: PJ
authors.lastname: Honeycutt
authors.forename: G
authors.initials: G
authors.lastname: Soori
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013629:Tamoxifen; D003606:Dacarbazine; D002945:Cisplatin; D002330:Carmustine