title: Chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha2b and interleukin-2 versus two cycles of dacarbazine followed by chemoimmunotherapy in patients with metastatic melanoma: a randomised phase II study of the European Organization for Research and Treatment of Cancer Melanoma Group.
abstract: BACKGROUND
  Chemoimmunotherapy for patients with metastatic melanoma is associated with high toxicity, and only a subset of patients will benefit. This randomised phase II study was performed with the primary objective of exploring whether two cycles of dacarbazine monotherapy could select the subset of patients that would benefit most from more intensive chemoimmunotherapy.
  
  
  METHODS
  Patients with metastatic melanoma were randomised to either receive chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha and interleukin-2 (arm A) or initial treatment with two cycles of dacarbazine monotherapy followed irrespective of response by the same 4-drug regimen of chemoimmunotherapy (arm B). Chemoimmunotherapy was continued in the absence of disease progression for a maximum of four cycles. Primary end-point was the disease stabilisation rate.
  
  
  RESULTS
  A total of 93 patients were randomised, and 89 patients were eligible. Disease stabilisation (complete/partial response or stable disease) was achieved in 19 patients (42.2%) in arm A and 9 patients (20.5%) in arm B. In arm B 32 of the 44 patients continued chemoimmunotherapy after two cycles of dacarbazine. Of 20 patients with progressive disease (PD) after two cycles of dacarbazine in arm B, only 2 patients achieved an objective response. Median overall survival (OS) in arms A and B was 10.5 months and 9.5 months, respectively.
  
  
  CONCLUSIONS
  Despite a lower initial stabilisation rate, the strategy of starting with 2 courses of DTIC prior to a 4-drug regimen led to comparable median overall survival. Only few transient responses were achieved with the 4-drug regimen in patients with disease progression on DTIC, suggesting frequent cross resistance. Two cycles of dacarbazine monotherapy cannot be recommended to select patients for more intensive chemoimmunotherapy.
authors.affiliation: Department of Medical Oncology, St. Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. c.punt@onco.umcn.nl <c.punt@onco.umcn.nl>
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: S
authors.initials: S
authors.lastname: Suciu
authors.forename: M A
authors.initials: MA
authors.lastname: Gore
authors.forename: J
authors.initials: J
authors.lastname: Koller
authors.forename: W H J
authors.initials: WH
authors.lastname: Kruit
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: P
authors.initials: P
authors.lastname: Patel
authors.forename: D
authors.initials: D
authors.lastname: Lienard
authors.forename: A M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D010349:Patient Compliance; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine; D002945:Cisplatin