A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin 2, and interferon alpha-2B in patients with metastatic melanoma

Clin Cancer Res. 2000 Jun;6(6):2201-8.

Abstract

In an effort to develop a biochemotherapy regimen for metastatic melanoma suitable for testing in a cooperative group setting, we modified the concurrent biochemotherapy regimen of S. S. Legha et al. (J. Clin. Oncol., 16: 1752-1759, 1998) by providing enhanced supportive care and developing a strict, conservative approach to the management of treatment-related toxicities. Patients received cisplatin, vinblastine, and dacarbazine (CVD: cisplatin (20 mg/m2) and vinblastine (1.2 mg/m2) on days 1-4, dacarbazine (800 mg/m2) on day 1 only) concurrently with interleukin 2 (9 MIU/m2/day) by continuous i.v. infusion on days 1-4 and IFN-alpha (5 MU/m2/day) on days 1-5, 8, 10, and 12. Prophylactic antibiotics and a maximum of four cycles were administered. Routine granulocyte colony-stimulating factor and aggressive antiemetics were initiated after patients 7 and 14, respectively. Forty-four patients were enrolled in this study. No patients had received prior chemotherapy or interleukin 2; however, 23 (53%) had received prior IFN-alpha, mostly in the adjuvant setting. A total of 131 treatment cycles was administered. Significant toxicities requiring dose modification included: hypotension requiring pressors (15 episodes in 11 patients), grades 3/4 vomiting (12 episodes in 15 cycles; 5 episodes in 12 patients (6 episodes in 9 cycles after initiation of the modified antiemetic regimen), transient renal insufficiency (5 episodes in 5 patients), grade 4 thrombocytopenia (24 episodes, 1 associated with bleeding), neutropenia with or without fever (15 instances, only 11 in 112 cycles after routine use of granulocyte colony-stimulating factor), and catheter-related bacteremia (2 patients). Five (16%) of 30 patients who were treated after the last protocol modification experienced what we defined as unacceptable toxicity for a cooperative group setting. Responses were seen in 19 of 40 evaluable patients (relative risk, 48%) with 8 complete responses (20%). The median response duration was 7 months (range, 1-17+ months) with one currently ongoing. The central nervous system was the initial site of relapse in 11 responding patients. The median survival duration was 11 months (range, 2-31 months). This modified, concurrent biochemotherapy regimen is active and tolerable for use in a cooperative group setting. Central nervous system relapse, however, remains a concern for responders. This regimen is being compared with CVD in a Phase III Intergroup Trial (Eastern Cooperative Oncology Group/Southwest Oncology Group 3695).

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Central Nervous System Neoplasms / secondary
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Combined Modality Therapy
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Disease-Free Survival
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Pilot Projects
  • Recombinant Proteins
  • Recurrence
  • Time Factors
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Interleukin-2
  • Recombinant Proteins
  • Vinblastine
  • Dacarbazine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cisplatin