Cisplatin and vinorelbine followed by ifosfamide plus epirubicin vs the opposite sequence in advanced unresectable stage III and metastatic stage IV non-small-cell lung cancer: a prospective randomized study of the Southern Italy Oncology Group (GOIM)

A multicentric, prospective phase III study was carried out with the aim of testing the so-called 'worst drug rule' hypothesis, which suggests the use of an effective but 'less active' regimen that first eradicates tumoral cells resistant to a second effective and 'more active' regimen. With respect to this hypothesis, we considered the cisplatin plus vinorelbine regimen (CCDP/VNR) as the more active regimen compared with the non-cisplatin-containing regimen of ifosfamide plus high-dose epirubicin (IFO/EPI). Thus, a randomized study was carried out to compare the sequencial strategy of three cycles of CDDP/VNR followed by three cycles of IFO/EPI with the opposite sequence in advanced non-sm…