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Previous Volume 340:351-357 February 4, 1999 Number 5 Next

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ABSTRACT

Background Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment.

Methods We conducted a case–control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups.

Results Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose–response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia.

Conclusions Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.

Source Information

From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md. (L.B.T., R.E.C.); Cancer Care Ontario, Toronto (E.J.H.); Karolinska University Hospital, Stockholm, Sweden (K.B., P.H.); the University of Iowa, Iowa City (C.F.L.); the Department of Health and Senior Services, Trenton, N.J. (B.A.K.); Helsinki University Central Hospital, Helsinki, Finland (T.W.); Danish Cancer Society, Copenhagen, Denmark (M.A.); Finnish Cancer Registry, Helsinki, Finland (E.P.); Princess Margaret Hospital, University of Toronto, Toronto (J.S.); and the University of Texas M.D. Anderson Cancer Center, Houston (M.S.). Other authors were Hans Storm, M.D., Danish Cancer Society, Copenhagen, Denmark; E. Aileen Clarke, M.D., Cancer Care Ontario, Toronto; John D. Boice, Jr., Sc.D., Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md.; and Mary Gospodarowicz, M.D., Princess Margaret Hospital, University of Toronto, Toronto.

Address reprint requests to Dr. Travis at the National Cancer Institute, Executive Plaza N., Suite 408, Bethesda, MD 20892.

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