Background Bisphosphonates are effective against the increasedbone resorption caused by certain diseases because they inhibitthe activity of osteoclasts. In patients who have breast cancerand metastatic bone disease, the bisphosphonate clodronate (clodronicacid) reduces the frequency of skeletal complications. Experimentsin animals and preliminary clinical observations indicate thatearly clodronate therapy reduces the incidence of new bony metastasesin breast cancer. We investigated the effects of clodronateon the incidence and extent of new metastases in patients withbreast cancer.
Methods Between 1990 and 1995, 302 patients with primary breastcancer and tumor cells in the bone marrow (the presence of whichis a risk factor for the development of distant metastases)were randomly assigned to receive clodronate at a dose of 1600mg per day orally for two years (157 patients) or standard follow-up(145 patients). The median length of observation was 36 months.All patients in both groups received standard surgical treatmentand customary hormonal therapy or chemotherapy.
Results Distant metastases were detected in 21 patients in theclodronate group and in 42 patients in the control group (P<0.001).The incidence of both osseous and visceral metastases was significantlylower in the clodronate group than in the control group (P=0.003for both osseous and visceral metastases). Six patients in theclodronate group died, as did 22 in the control group (P=0.001).The mean number of bony metastases per patient in the clodronategroup was roughly half that in the control group (3.1 vs. 6.3).
Conclusions Clodronate can reduce the incidence and number ofnew bony and visceral metastases in women with breast cancerwho are at high risk for distant metastases.
Source Information
From the Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg (I.J.D., E.-F.S., C.G., R.G., D.W., G.B.); and the Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt (S.D.C., M.K.) — both in Germany.
Address reprint requests to Dr. Diel at the Department of Obstetrics and Gynecology, University Hospital, Voss Strasse 9, 69115 Heidelberg, Germany.
Clodronate in Metastatic Breast Cancer
Meli M., Rausa L., Panasci L. C., Sandor V., Melnychuk D., Atkins C. D., Diel I. J., Costa S. D., Kaufmann M.
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N Engl J Med 1998;
339:1940-1941, Dec 24, 1998.
Correspondence
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