Purpose: Systemic therapy for metastatic melanoma includes chemotherapy, either with dacarbazine alone or a multiagent combination regimen, and biologic therapy with recombinant interferon-alpha and/or recombinant interleukin-2. However, neither of these treatment options has produced long-term control of disease except on rare occasions. We have therefore developed a combined biochemotherapy program in an effort to improve long-term control of metastatic melanoma.
Patients and methods: Between October 1990 and October 1993, we treated 115 patients with a triple-drug chemotherapy regimen--CVD (cisplatin, vinblastine, dacarbazine)--in combination with biotherapy using recombinant interleukin-2 and recombinant interferon-alpha. This program of biochemotherapy has evolved from an initial protocol of sequential use of CVD followed by biotherapy, called sequential biochemotherapy, to a more recent protocol of concurrent administration of all five drugs, called concurrent biochemotherapy. Sixty-two patients have been treated with the sequential regimen and 53 patients with the concurrent regimen.
Results: Among the 114 evaluable patients, we have observed 24 complete responses (21%) and 45 partial responses (39%) for an overall response rate of 60%. From the group of 24 complete responders, 12 patients (10% of the total) have achieved long-term remissions and have remained disease free for periods of time ranging from 4+ to 6+ years.
Conclusion: Although the overall results of sequential versus concurrent biochemotherapy are similar, the toxicity appears to be less severe in patients treated with the concurrent regimen. The overall median survival of patients treated with biochemotherapy appears to be longer compared with our previous experience with CVD chemotherapy used alone (12 vs 9 months). Based on the encouraging results obtained with biochemotherapy, phase III studies have been initiated to compare prospectively biochemotherapy with chemotherapy (CVD regimen) alone.