Combination of chemotherapy with interleukin-2 and interferon-alfa for the treatment of advanced melanoma.

The antitumor activity of available chemotherapy regimens against advanced melanoma is modest. Likewise, the results with biologic response modifiers such as interleukin-2 (IL-2) and interferon-alfa (IFN-alpha), used alone or in combination, also have been disappointing, although some patients experience very durable remissions. However, the combination of cisplatin-based chemotherapy with IL-2 plus IFN-alpha, referred to as biochemotherapy, has shown encouraging preliminary results. Investigators at M.D. Anderson Cancer Center have conducted a series of phase II studies exploring different schedules of chemotherapy administration using a regimen of cisplatin, vinblastine, and dacarbazine (CVD) and IL-2 plus IFN-alpha (biotherapy). Alternating CVD with biotherapy every 6 weeks produced a response rate similar to that obtained by using CVD alone. The administration of biotherapy immediately after CVD followed by a sandwich of biotherapy/CVD/biotherapy appears to be superior to CVD alone. Finally, the administration of biotherapy concurrently with CVD also appears to be superior to CVD alone. Similar results were observed by other investigators using a cisplatin-based regimen in combination with IL-2 plus IFN-alpha. The mechanism of antitumor effect of biochemotherapy remains unclear. Preliminary results of laboratory studies performed at M.D. Anderson Cancer Center suggest that the biotherapy may act by enhancing the cytotoxic effect of CVD, possibly by activation of tumor-infiltrating macrophages, which release pro-oxidants that affect the DNA repair process of the tumor cells. Collectively, these clinical and laboratory findings indicate that biotherapy may be synergistic with cisplatin-based regimens and that the sequence of administration appears to be important.