RANDOMIZED TRIAL OF CHEMOTHERAPY AND RADIATION-THERAPY WITH OR WITHOUT WARFARIN FOR LIMITED-STAGE SMALL-CELL LUNG-CANCER - A CANCER AND LEUKEMIA GROUP-B STUDY

Purpose: Studies by the Veterans Administration Cooperative Studies pr ogram and Cancer and Leukemia Group B (CALGB) suggested that the addit ion of warfarin to chemotherapy knight enhance response and/or surviva l in small-cell lung cancer (SCLC). This randomized study evaluated th e effect of warfarin with chemotherapy and radiation therapy in limite d-stage SCLC. Patients and Methods: patients were randomized to receiv e warfarin or no warfarin. All patients received three cycles of doxor ubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplat in, cyclophosphamide, and etoposide [PCE]) were given concurrently wit h radiation therapy, Three cycles of ACE were given after chemoradiati on therapy, but were discontinued due to ct high rate of pulmonary tox icity. Results: There were no significant differences in response rate s, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated ansi control groups, in patie nts treated according to the initial design, an increase in failure-fr ee survival seen with warfarin treatment approached significance (P = .07), Preamendment results, while not significant, did not have superi mposable treatment survival curves. a landmark analysis at 8 months sh owed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with less than or equal to 13.75 months for complete or partial responders not treated with w arfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103), Conclusion: Warfarin does not appear to improve outcome significantly-in limited-s tage SCLC. However, the differences in some variables between populati ons before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies. (C) 1997 by American S ociety of Clinical Oncology.