title: Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma.
abstract: OBJECTIVE
  To evaluate the antitumor activity and toxicity of concurrent biochemotherapy that uses cisplatin, vinblastine, and docarbazine (DTIC) (CVD) in combination with interferon alfa-2a (IFN-alpha) and interleukin-2 (IL-2) in patients with metastatic melanoma.
  
  
  METHODS
  Between October 1992 and October 1993, 53 patients with a documented diagnosis of metastatic melanoma with measurable lesions and an Eastern Oncology Cooperative Group (ECOG) performance status of 2 or less were enrolled onto this study. Patients were required to have no clinically significant cardiac dysfunction and to be free from symptomatic brain metastases. The treatment consisted of cisplatin 20 mg/m2 daily for 4 days; vinblastine 1.6 mg/m2 daily for 4 days; and DTIC 800 mg/m2 intravenously (i.v.) day 1 with IL-2 9 x 10(6) IU/m2 i.v. by continuous infusion daily for 4 days and IFN-alpha 5 x 10(6) U/m2 subcutaneously daily for 5 days, repeated at 21-day intervals. Response was assessed after two cycles and patients who responded were continued on treatment for a total of six cycles.
  
  
  RESULTS
  Among 53 assessable patients, 11 patients (21%) achieved a complete response (CR) and 23 patients (43%) achieved a partial response (PR), for an overall objective response rate of 64%. The median time to disease progression for all patients was 5 months. The median survival of all patients entered onto the trial was 11.8 months. Among the 11 patients who achieved a CR, five patients (9%) have remained in continuous CR for 50+ to 61+ months. The toxicity of biochemotherapy consisted of severe myelosuppression, significant nausea and vomiting, and moderately severe hypotension that required inpatient hospital care for each 5-day cycle of treatment. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  Concurrent biochemotherapy for patients with advanced melanoma is capable of producing high CR and overall response rates and resulted in durable complete remissions in a small fraction of patients. Toxicity, although severe, was manageable in a routine inpatient hospital environment.
authors.affiliation: Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. slegha@notes.mdacc.tmc.edu
authors.forename: S S
authors.initials: SS
authors.lastname: Legha
authors.forename: S
authors.initials: S
authors.lastname: Ring
authors.forename: O
authors.initials: O
authors.lastname: Eton
authors.forename: A
authors.initials: A
authors.lastname: Bedikian
authors.forename: A C
authors.initials: AC
authors.lastname: Buzaid
authors.forename: C
authors.initials: C
authors.lastname: Plager
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin