Alternating combination chemotherapy regimens in small-cell lung cancer

Although many combination chemotherapy regimens are capable of inducing rapid tumor regression and improved survival in patients with small-cell lung cancer (SCLC), death from recurrent chemotherapy-resistant disease remains the inevitable outcome in over 90% of cases. There have been several attempts to overcome this problem of drug resistance by the administration of two or more combination regimens in various types of alternating schedules. However, this treatment strategy has not achieved the kind of success observed in other tumor types. Several factors may account for this failure. The regimens employed may have lacked sufficient non-cross resistance and relative efficacy. Furthermore, consideration of the biologic processes involved in the regulation of tumor cell growth, heterogeneity, and drug resistance suggests that the time interval between alternating combinations should be as short as possible. Data indicate that combination cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV), and combination cisplatin and VP-16 (PVP) are highly active and not totally cross resistant in patients with SCLC. An induction regimen consisting of CAV rapidly alternating with PVP has been studied in 44 patients. Treatment was well tolerated and the regimens could be alternated at intervals of less than 3 weeks. A 95% objective response rate and 67% complete response rate was achieved. These results appear to be better than previous results with CAV or PVP used alone as induction therapy. A randomized trial is required to confirm this impression.