Random prospective study cyclophosphamide, doxorubicin, and methotrexate (CAM) combination chemotherapy versus...

A group of 104 patients with unresectable non-small cell lung cancer were randomized to receive combination chemotherapy with cyclophosphamide, doxorubicin, and methotrexate (CAM) or single-agent sequential chemotherapy with the same three agents. CAM combination chemotherapy produced a 22% objective response rate, including two complete remissions, compared to a 9% response rate, including one complete remission, produced by single-agent therapy (P = 0.16). The median survival time was 32 weeks (range, 3-116) for CAM, compared to 25 weeks (range, 4-179 +) for sequential single agents (P = 0.24). Overall survival was 31% (1-year), (16%) (1 1/2-year), and 5% (2-year), with no difference between the study arms. Although there was no statistically significant survival advantage for the CAM arm, both arms had survival superior to that in historical controls, presumably because of better patient selection. This study indicates that cyclophosphamide, doxorubicin, and methotrexate are, at best, marginally active as single agents, and new drugs with more efficacy are needed before combination chemotherapy can be expected to result in any meaningful prolongation of survival in non-small cell lung cancer.