Testing the possible non-cross resistance of two equipotent combination chemotherapy regimens against small-cell lung cancer: a phase II study of the EORTC Lung Cancer Cooperative Group.

The Goldie-Coldman hypothesis of alternating non-cross resistant combination chemotherapy regimens for small-cell lung cancer has never been adequately evaluated. In previously reported studies non-cross resistance and/or equipotency of the combinations used had not been tested before the phase III study was started. We describe two combination chemotherapy regimens with comparable efficacy against small-cell lung cancer and present a phase II test of their possible non-cross resistance. Patients clinically resistant to cyclophosphamide, doxorubicin and etoposide (CDE), were treated with the second-line regimen consisting of vincristine, ifosfamide, mesna and carboplatin (VIMP) (n = 25). This resulted in 1 complete and 14 partial responses, response rate 60% [95% confidence interval (CI): 38.7-78.9%]. Patients clinically resistant to vincristine, carboplatin (n = 22) or ifosfamide, mesna, carboplatin (n = 21) were treated with CDE, resulting in 6 complete responses and 16 partial responses, response rate 51% (95% CI: 35.5-66.7%). The clinical value of such a degree of non-cross resistance has to be evaluated in a phase III study.