Biochemotherapy with carmustine, cisplatin, dacarbazine, tamoxifen and low-dose interleukin-2 for patients with metastatic malignant melanoma.

Background: The toxicity and efficacy of biochemotherapy with low-dose interleukin-2 for patients with metastatic malignant melanoma (MM) were studied.

Method: Metastatic chemo-naive MM patients were given biochemotherapy (BCDT regimen) with carmustine (BCNU), cisplatin (CDDP), dacarbazine (DTIC), and tamoxifen and interleukin-2 (IL-2) 18 Million International Units in divided doses by subcutaneous injection three times a week for four weeks. BCDT consisted of BCNU (150 mg/m2, day l every 8 weeks), CDDP (25 mg/m2, days l-3 every 4 weeks), DTIC (220 mg/m2, days 1-3 every 4 weeks) and tamoxifen 10 mg twice a day. Treatment was repeated for a total of 6 cycles, or until disease progression or unbearable toxicity.

Results: From Nov 2001 to July 2005, 40 patients (20 men; 20 women) were enrolled. Their median age was 54 years (range 22-79 years). Subtypes of melanoma included 23 (57.5%) acral lentiginous, 11 (27.5%) nodular, 1 (2.5%) mucosal, and 5 (12.5%) others. Grade 3-4 toxicities included neutropenia (27.5%), anemia (45%), and thrombocytopenia (40%). Constitutional IL-2 toxicities included indurate injection site (57.5%), fever (60%), chills (55%), itchy skin (42.5%), bone pain (32.5%) and myalgia (45%). Grade 1-2 hypotension was noted in 12.5% of patients. Eosinophilia (range 5% to 71%) was evident in 72.5% of patients. The response rate was 32.5% including 5% with a complete response, 27.5% with a partial response, and 17.5% with stable disease. The median progression-free survival was 6.2 months (95% CI: 2.9~9.6 months). The median overall survival was 11.3 months (95% CI: 7.0~15.6 months). Five patients (12.5%) who presented with oligo-metastasis achieved five-year survivals.

Conclusions: Our data demonstrated that low-dose IL-2 plus BCDT is tolerable. A durable response and long-term survival can be achieved in a small subgroup of patients.