A phase II study of combined administration of dacarbazine and carboplatin with home therapy of recombinant interleukin-2 and interferon-?2a in patients with advanced malignant melanoma

Abstract

Chemotherapy and interleukin-2 (IL-2) and/or interferon alpha (IFN alpha) produce objective responses in a proportion of patients with advanced malignant melanoma. The duration of response to chemotherapy is usually less than 4 months, and immunotherapy has resulted in long-lasting remissions in a small number of patients with metastatic melanoma. The current study was conducted to improve the antitumor efficacy and the interactions between recombinant (r) IL-2, rIFN alpha 2a and chemotherapy. A total of 16 evaluable patients with metastatic malignant melanoma were entered into a phase-II study designed to assess the response rate and therapeutic efficacy of dacarbazine and carboplatin followed by rIL-2 and rIFN alpha 2a. Patients received 750 mg/m2 dacarbazine with 400 mg/m2 carboplatin each by intravenous bolus on days 1 and 22. Recombinant IL-2 and IFN alpha 2a were administered on an outpatient basis (home therapy) subcutaneously for 6 consecutive weeks: 4.8 x 10(6) IU/m2 rIL-2 daily, 5 days a week; 6.0 x 10(6) IU/m2 rIFN alpha 2a thrice weekly. There were responses in 6 of the 16 enrolled patients with an overall response rate of 37.5% (95% confidence interval: 14%-61%). All responding patients had partial responses. The median survival time of the responding patients was significantly better than that of patients with progressive and stable disease (P = 0.03). The median duration of response was 11 months (range 2-24 months). Responses in lung, liver, soft tissue and lymph-node sites were noted.

Strategies for Combining Chemotherapy and Biotherapy in Melanoma

“…Following initial encouraging reports, 6 several groups examined the use of cytotoxic agents, especially cisplatin-based regimens in combination with IL-2 plus IFN-a to treat patients with advanced melanoma. [7][8][9][10][11][12][13][14] These results seemed superior to any previously published biochemotherapy regimens ( Table 1). The treatment schema of select biochemotherapy regimens is shown in Fig 1. In most biochemotherapy studies, IL-2 has been administered by the intravenous route (Table 1).…”

“…Experience with biochemotherapy using IL-2 by the subcutaneous route is more limited ( Table 1). [12][13][14] Overall, the preliminary results are promising but appear slightly inferior to the intravenous IL-2-based studies. Further study of outpatient biochemotherapy is needed, as reductions in toxicity and cost are also important considerations.…”