Chemotherapy use and risk of bone marrow suppression in a large population-based cohort of older women with breast and ovarian cancer

Abstract

We studied 65,521 women with breast cancer and 7,420 women with ovarian cancer aged ≥ 65 identified from the 16 areas of the Surveillance, Epidemiology and End Results program linked with Medicare data during 1991-2002. Bone marrow toxicity associated with chemotherapy was defined using diagnosis codes from Medicare inpatient, outpatient and physician claims. The time to event Cox regression was utilized to estimate the risk of bone marrow toxicity. Use of anthracyclines, taxanes or platinums was associated with increased risks of short- (≤3 months) and long-term (>3 months) anemia and neutropenia in patients with breast cancer. Alkylating agents or antimetabolites were additional significant predictors of anemia in women with ovarian cancer. Patients who received chemotherapy (irrespective of regimens) were twice (breast cancer) or three times (ovarian cancer) as likely to develop thrombocytopenia compared to those not receiving chemotherapy. Among women with breast cancer, patients receiving cyclophosphamide, methotrexate and fluorouracil regimens (hazard ratio=19.0, 95% CI=11.2-32.5), platinum/taxane therapy (21.9, 11.9-40.4) or the cyclophosphamide, adriamycin and fluorouracil regimen (32.5, 19.6-53.9) were strongly associated with risk of aplastic anemia. There was a dose-response relationship between the use of taxane or platinum and the risk of bone marrow suppression, whereas the increased risk of bone marrow toxicity was consistently higher in those with use of alkylating agents or anthracycline-based regimens irrespective of the increasing number of cycles received. In conclusion, there was an association between chemotherapy use and clinical manifestations of bone marrow toxicities in a population-based setting.