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.

<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies. </jats:p></jats:sec>