ADJUVANT CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE, DOXORUBICIN, AND CISPLATIN IN PATIENTS WITH COMPLETELY RESECTED STAGE-I NONSMALL CELL LUNG-CANCER - AN LCSG TRIAL

Objective: Two recent studies in resectable non-small cell lung cancer by the Lung Cancer Study Group (LCSG) suggested an advantage to adjuv ant therapy with cyclophosphamide, doxorubicin (Adriamycin), and cispl atin (CAP). Neither study had a no-treatment control arm. The purpose of this study was to compare the CAP regimen with no treatment in pati ents with resectable early-stage non-small cell lung cancer. Methods: After complete resection, eligible patients with T1N1 or T2N0 non-smal l cell lung cancer were randomly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after sur gery after stratification for histology, preoperative white blood cell count, and Karnofsky performance status before surgery. The CAP regim en consisted of 400 mg/m(2) of cyclophosphamide, 40 mg/m(2) of doxorub icin, and 60 mg/m(2) of cisplatin. Of the 269 eligible patients entere d in the study, 101 had recurrence and 127 had died at the time of ana lysis. The mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overa ll survival between the two groups even when analyses were adjusted fo r prognostic variables. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles an time. Among the patients who had recurrences, 74% had their initial recurrence at a distant site. Conclusion: No survival benefit for CAP vs no-treatment control was found in this study. Therefore, ad juvant therapy with CAP should not be recommended for patients with re sected early-stage non-small cell lung cancer. Further trials to test adjuvant therapy are indicated, but investigators should use better an tiemetics to improve patient compliance as well as more active cisplat in-based chemotherapy regimens.