INCREASED THROMBOEMBOLIC COMPLICATIONS WITH CONCURRENT TAMOXIFEN AND CHEMOTHERAPY IN A RANDOMIZED TRIAL OF ADJUVANT THERAPY FOR WOMEN WITH BREAST-CANCER

Purpose and Methods: Associations between thromboembolism and malignan cy, usually widespread, and between thromboembolism and hormonal and/o r chemotherapy have been previously reported. We performed a randomize d trial of tamoxifen 30 mg/d for 2 years (T) versus T plus 6 months of intravenous chemotherapy with cyclophosphamide, methotrexate, and flu orouracil (CMF) for postmenopausal women with involved axillary nodes and positive estrogen receptor (ER) or progesterone receptor (PSR) sta tus following primary therapy for breast cancer. Results: We observed one or more thromboembolic events in 48 of 353 women (13.6%) allocated to receive T plus CMF in comparison to five of 352 women (2.6%) rando mized to receive T alone (P < .0001). Six women in the T plus CMF arm, but none randomized to receive T alone, suffered two thromboembolic e vents while on study therapy. There were also significantly more women who developed severe (grade 3 to 5) thromboembolic events in the T pl us CMF arm than in the T arm (34 v five; P < .0001). Most thromboembol ic events (39 of 54) occurred while women were actually receiving chem otherapy (P < .0001). Thromboembolic complications resulted in more da ys in hospital and more deaths than any other complication of therapy, including infection, in this trial. Conclusion: Thromboembolism relat ed to the addition of CMF chemotherapy to tamoxifen as adjuvant therap y in this group of women represents a relatively common and serious co mplication that may outweigh any benefits offered by this additional t herapy. (C) 1996 by American Society of Clinical Oncology.