Chemotherapy for inoperable, non-small cell bronchogenic carcinoma: EST 2575, generation II.

Between 1976 and 1978 the Eastern Cooperative Oncology Group tested ten regimens in 415 patients with histologically documented, inoperable non-small cell bronchogenic carcinoma. Most patients were ambulatory (69%) and had extensive disease (69%). Patients were stratified by cell type: squamous cell carcinoma (SQ), large cell anaplastic carcinoma (LC), or adenocarcinoma (AD). Ineffective single agents (including cell types tested and percent complete and partial responses) were dactinomycin (SQ, 6%), dianhydrogalactitol (SQ, 0), ftorafur (AD and LC, 3%), and piperazinedione (AD and LC, 7%), Ineffective combination regimens included the contemporary standard regimen cyclophosphamide (CYT) plus CCNU (SQ, AD, and LC, 9%), methotrexate plus doxorubicin (ADR) plus CYT plus CCNU (MAC) (SQ and AD, 12%), and mitolactol plus ADR (AD and LC, 8%). When compared to CYT plus CCNU the following regimens demonstrated significant activity: CYT plus bleomycin plus cisplatin (SQ, 23%; P = 0.02) and ADR plus 5-FU plus cisplatin (AD and LC, 24%; P = 0.006). Mitomycin demonstrated marginal activity in squamous cell cancer (19%, P = 0.06). Neither "active" regimen improved survival although responders to any regimen had a significant prolongation of median survival (31.6 vs 15.7 weeks, P = 0.002). The MACC regimen, piperazinedione, and mitomycin were substantially more toxic than the two effective regimens, which were adequately tolerated. Ambulatory performance status, limited disease, and prior surgery were significant positive prognostic variables whereas prior radiation and pretreatment weight loss adversely affected response or survival.