Phase II Trial of Subcutaneous Interleukin-2,Subcutaneous Interferon-α,Intravenous Combination Chemotherapy,and Oral Tamoxifen in the Treatment of Metastatic Melanoma: Final Results of Cancer Biotherapy Research Group 94-11

Abstract

Background

The treatment of metastatic melanoma remains unsatisfactory despite encouraging results with biotherapy and combination chemotherapy. Combining these two modalities may improve outcomes for such patients.

Methods

Eligible patients had metastatic melanoma, were in good medical condition, and had not been treated previously for metastatic disease. A 42-day treatment cycle consisted of: tamoxifen 10 mg p.o. b.i.d. days 1-42, carmustine 150mg/m² i.v. on day three, dacarbazine 220 mg/m² and cisplatin 25 mg/m² i.v. q.d. days 3-5, and 24-26, interferon-α2b 6.0 MU/m² s.c. days 8-12 and 29-33, and interleukin-211 MU/m² s.c. days 8,10,12 and 29,31,33. In the absence of tumor progression, patients could receive up to six cycles of alternating treatment. Toxicity and tumor response was assessed following each treatment cycle; survival was determined from the first date of treatment.

Results

The 28 melanoma patients included 21 men and 7 women, with a median age of 55 years with a range of 26-77. Fifty-four percent were asymptomatic when treatment was initiated. Eighty percent had soft tissue metastases, 32% lung, 28% liver, and 8% bone. There were nine patients with significant tumor responses (three complete, six partial) for a response rate of 32% (18-57% 95% CI) based on intent-to-treat analysis, and 38% (18-57%, 95% CI) for the 24 patients who were evaluable for response. The months of duration of survival for responders were 38.9+, 27.2+, 22.8+, 16.3, 13.2, 9.4, 7.5, 6.5+, and 5.8. At a median follow-up of 31 months, the median duration of event-free survival was 4.6 months; median survival was 9.4 months. The survival rate one year from initiating treatment was 42%; 2-year survival was 14%. The most frequent toxicities were 96% nausea/vomiting, 80% fatigue, 73% thrombocytopenia, 60% neutropenia, and 44% fever. Two patients experienced early death that may have been treatment related; one died of cardiovascular complications and the other of a central nervous system event.

Conclusion

This outpatient regimen was associated with significant toxicity including a 7% rate of possible treatment-related death. Tumor regression rates and survival were similar to results reported for chemotherapy alone, or inpatient IL-2-based therapy, but did not suggest an improvement in outcome.