Metastatic non-small cell bronchogenic carcinoma: a randomized trial of sequential vs combination chemotherapy

In order to determine whether combination chemotherapy offered any advantage over single-agent therapy in cases of metastatic non-small cell bronchogenic carcinoma, we performed a randomized study in 56 patients comparing combination chemotherapy (cyclophosphamide, doxorubicin, methotrexate, procarbazine, leucovorin-CAMP-L) with a regimen in which the same drugs were given sequentially (methotrexate/leucovorin followed by cyclo-phosphamide/doxorubicin at progression). Of the patients receiving the combination, 52% (14 of 27) had either a partial response or stable disease, compared to 17% (5 of 29) in the sequential group. Of the patients with adenocarcinoma, those in the combination group had a significantly longer survival than those treated in the sequential group (medians, 10.0 vs 2.8 months; P < 0.01); such a difference could not be demonstrated for patients with squamous carcinoma. Patients who achieved a partial response had a median survival of 15.3 months; those with stable disease survived a median of 10.0 months; and those with no response survived a median of 2.5 months (P < 0.0001). Four patients died from chemotherapy-related complications: three from methotrexate toxicity and resultant infection and one from pneumonia associated with neutropenia. We conclude that the short survival of non-responding patients and the survival benefit accompanying response or stabilization make early aggressive combination therapy useful for patients with metastatic non-small cell lung cancer.