title: Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon alpha.
abstract: OBJECTIVE
  A therapeutic lyophilized melanoma vaccine consisting of two mechanically disrupted allogeneic melanoma cell lines and the immunological adjuvant Detox-PC (Melacine) has demonstrated encouraging activity in metastatic malignant melanoma, often in regimens containing pretreatment with low-dose cyclophosphamide. In addition, IFN-alpha2b (INTRON A; Schering-Plough Corporation, Kenilworth, NJ) has shown efficacy in melanoma refractory to Melacine. In this Phase II trial, the combination of cyclophosphamide, Melacine, and IFNalpha was tested in metastatic malignant melanoma.
  
  
  METHODS
  Eligibility criteria included measurable disease, no prior systemic therapy for a minimum of 4 weeks, and adequate marrow, renal, and hepatic function. Cyclophosphamide was administered once at a dose of 300 mg/m(2) i.v. on day -3 before the first dose of Melacine. Melacine was administered at a dose of 2 x 10(7) tumor cell equivalents per dose admixed with 0.25 ml of Detox-PC s.c. once a week on weeks 1-4 and week 6. Melacine maintenance was then given monthly from the 8th week, until progression or intolerable toxicity. IFN was started in the evening after the fourth dose of Melacine at a dose of 5,000,000 units/m(2) 3 times a week, and continued until progression.
  
  
  RESULTS
  Forty-seven patients were enrolled, of whom 39 completed the full course and were considered evaluable. The toxicity of the regimen was minimal and consisted mainly of pain at injection sites and granulomas caused by Detox-PC, and constitutional symptoms attributable to IFN. In 39 evaluable patients, the overall objective response rate was 10.2%, but 64% of patients had stabilization of their disease for at least 16 weeks. The median time to disease progression in evaluable patients was 8 months [95% confidence interval (CI), 6-13 months]. Median survival time for all of the 47 patients enrolled was 12.5 months (95% CI, 8-15 months) with a median time to disease progression of 4 months (95% CI, 3-7 months).
  
  
  CONCLUSIONS
  Despite a low objective response rate, this combination holds great promise because of its tolerability and the high proportion of prolonged durations of remission or disease stabilization that it elicited.
authors.affiliation: Karmanos Cancer Institute, Department of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: Judith
authors.initials: J
authors.lastname: Abrams
authors.forename: Denise
authors.initials: D
authors.lastname: Darrah
authors.forename: Vicky
authors.initials: V
authors.lastname: Jones
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008207:Lymphatic Metastasis; D008222:Lymphokines; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008222:Lymphokines; C116434:Melacine; D011994:Recombinant Proteins; C022780:allogenic effect factor; D003520:Cyclophosphamide