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.

Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats

“…Together, these results suggest that CEF treatment caused bone marrow suppression and adipocyte expansion without affecting adipocyte differentiation. The finding of reduced bone marrow cellularity is in agreement with clinical studies which indicate a dose-response relationship between administration of anthracycline-based regimens and risk of bone marrow suppression in breast cancer patients, and a direct association between the number of treatment cycles and bone marrow toxicity [8]. Fat cells occupying haematopoietic marrow following chemotherapy is a common diagnostic feature in patients receiving chemotherapy.…”

“…Apart from the indirect adverse effects on bone, bone marrow toxicity is also commonly reported in breast cancer survivors. A recent population-based observational study found a dose-response relationship between administrations of anthracycline-based regimens and a risk of bone marrow suppression in those with breast cancer, with possible irreversible loss of bone marrow function from non-cell-cycle dependent drugs such as alkylating agents and anthracyclines [8]. Clinically, patients receiving chemotherapy and irradiation treatment have also been reported to have an increased marrow fat content [9].…”

New Insights on Glucosylceramide Synthase in Cancer Drug Resistance and Myelosuppression

“…Decreased BMSCs, which include mesenchymal stem cells and hematopoietic stem cells, are cause of myelosuppression that not only limits the treatments but also is a risk factor for poor prognosis, as it substantially diminishes the immunity [14,15]. Consistent with previous reports that Dox causes myelosuppression [16,17], we found Dox significantly decreased the numbers of BMSCs of tumor-bearing mice either in 6-days or in 42-days treatments [1].…”

Structural modifications in the sugar moiety as a key to improving the anticancer effectiveness of doxorubicin

“…Unfortunately, despite the clinical benefits of DOX, its use is often limited by serious adverse effects, such as severe cardiotoxicity and myelosuppression [5,9,10]. Severe dose-dependent cardiotoxicity occurs in~50% of patients treated with DOX.…”