Complications associated with erythropoietin-stimulating agents in patients with metastatic breast cancer: a Surveillance, Epidemiology, and End Results-Medicare study.

BACKGROUND: The authors evaluated the patterns of use and the risk of thromboembolic events (TEE) associated with erythropoietin-stimulating agents (ESAs) in older patients with metastatic breast cancer who were receiving chemotherapy. METHODS: The study was retrospective and used the SEER-Medicare linked database. Stage IV breast cancer patients diagnosed from 1995-2005, treated with chemotherapy, ≥66 years old, with full coverage of Medicare A and B were included. The World Health Organization's International Classification of Diseases (ICD-9) and the Healthcare Common Procedure Coding System (HCPCS) were used to identify the use of ESAs, chemotherapy, and complications of therapy. Analyses included descriptive statistics and logistic regression. RESULTS: Of 2266 women, 980 (43.3%) received ESAs, and 1286 (56.7%) did not. Patients diagnosed after 1999 or who received treatment with taxanes, anthracyclines, or vinorelbine were more likely to receive ESAs. Patients receiving ESAs had higher rates of stroke (18.5% vs 15.1%, P = .031); deep-vein thrombosis (DVT; 21.3% vs 14.4%, P<.001), other/unspecified thromboembolic event (TEE; 19.8% vs 14.7%, P = .001), and any clot (31.3% vs 23.4%, P<.0001). In multivariate analysis, patients receiving ESAs had increased risk for DVT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.75), and any clot (OR, 1.26; 95% CI, 1.02-1.57). A dose-dependent effect was evident for stroke, DVT, other TEE, and any clot. CONCLUSIONS: In this cohort of patients, the use of ESAs increased the risk of TEEs, with a dose-dependent effect for stroke, DVT, other TEE, and any clot. The data show that among patients treated with chemotherapy and ESAs for metastatic breast cancer, TEEs are a common event. Therefore, caution is recommended when using these agents.

Pixantrone dimaleate in combination with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: phase 1 study with a dose-expansion cohort.

BACKGROUND: Pixantrone dimaleate (pixantrone) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models. FND-R, a combination regimen of fludarabine, mitoxantrone, dexamethasone, and rituximab, has been shown to be an effective regimen for low-grade lymphomas. METHODS: This dose-escalation study, with an expansion cohort, was conducted to evaluate the safety and preliminary efficacy of FPD-R, in which pixantrone was substituted for mitoxantrone in the FND-R regimen, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (NHL). Escalated doses of pixantrone were administered to newly enrolled patients on day 2 of each 28-day cycle of FPD-R. RESULTS: Twenty-eight of 29 enrolled patients received at least 1 cycle of FPD-R (median, 5 cycles). Pixantrone 120 mg/m(2) was identified as the recommended dose in this regimen. Grade 3-4 adverse events were primarily hematologic; grade 3-4 lymphopenia occurred in 89% of patients and leukopenia in 79%. No patients developed congestive heart failure or grade 3-4 cardiac adverse events. Left ventricular ejection fraction decreases occurred in 8 (29%) patients, and most were grade 1 or 2, transient, and asymptomatic. The overall response rate was 89%. Estimated survival was 96% after 1 year and 92% after 3 years. CONCLUSIONS: The FPD-R regimen was well-tolerated and highly active in patients with relapsed or refractory indolent NHL.

Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer.

PURPOSE: To evaluate whether diabetes affects patterns of adjuvant chemotherapy use, toxic effects of chemotherapy, and breast cancer outcomes. PATIENTS AND METHODS: By using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged 66 years or older who had stages I through III breast cancer that was diagnosed between 1992 and 2002. Multivariable regression analyses were performed to determine the effect of diabetes on use of chemotherapy, toxicities, and outcomes. The risks of all-cause mortality and breast cancer-specific (BCS) mortality were estimated with the Kaplan-Meier method. RESULTS: Our cohort had 70,781 men and women, of whom 14,414 (20.36%) had diabetes. Among people who received chemotherapy (n = 11,826), 21.0% were diabetics. In this group, diabetics had lower odds of receiving anthracyclines (odds ratio [OR], 0.78; 95% CI, 0.71 to 0.87) and taxanes (OR, 0.86; 95% CI, 0.75 to 0.99). Diabetes was associated with increased odds of being hospitalized for any chemotherapy toxicity (OR, 1.38; 95% CI, 1.23 to 1.56), for infection or fever (OR, 1.43; 95% CI, 1.2 to 1.7), for neutropenia (OR, 1.22; 95% CI, 1.03 to 1.45), for anemia (OR, 1.24; 95% CI, 1.05 to 1.47), and for any cause (OR, 1.32; 95% CI, 1.19 to 1.46). Patients with diabetes had higher all-cause mortality (hazard ratio [HR], 1.35; 95% CI, 1.31 to 1.39). There was a significant interaction between diabetes and chemotherapy use for BCS mortality. Diabetic and nondiabetic patients who did not receive chemotherapy had similar BCS mortality, but diabetic patients who did receive chemotherapy had higher BCS mortality than nondiabetic patients (OR, 1.20; 95% CI, 1.07 to 1.35). CONCLUSION: In this observational, hypothesis-generating study, patients who have breast cancer and diabetes are at increased risk of chemotherapy-related toxicities compared with nondiabetic patients who are receiving chemotherapy and have higher all-cause mortality.

Completion of adjuvant radiation therapy among women with breast cancer.

BACKGROUND: Optimal treatment for breast cancer often involves lengthy multimodality care including 5 to 6 weeks of radiotherapy, but few studies have evaluated adherence to radiotherapy outside the context of a therapeutic clinical trial. METHODS: Using a SEER-Medicare database, the authors identified women age 66 years or older with Stage I to III breast cancer diagnosed between 1992 and 2002. They evaluated rates of completion of radiotherapy, defined as a minimum of 25 sessions. Multivariate logistic regression analyses were performed to determine factors associated with completion of radiotherapy, and Cox multivariate models were used to determine the impact of radiotherapy completion on local recurrence. RESULTS: Some 24,510 patients were included in the study. Eighty-seven percent of patients completed 25 or more radiotherapy sessions. In multivariate logistic regression models, mastectomy (HR 1.26, 95% CI 1.10-1.43), hospitalization during treatment (2.87, 2.49-3.31), earlier year of diagnosis, and black race (1.36, 1.14-1.63) were associated with increased risk of non-completion of radiotherapy. Among 21,269 patients treated with breast conservation, incomplete radiotherapy was associated with higher risk of local recurrence. A total of 96.6% [corrected] of patients who did not complete radiation therapy were free of recurrence at 5 years vs. 97.5% of patients who completed radiation therapy (HR 1.46, CI 1.09-1.95). CONCLUSION: This study demonstrates relatively high rates of completion of radiation therapy among a population of older woman with breast cancer. However, those who did not complete a full course of radiotherapy had small but statistically significant higher risk of breast cancer recurrence. Future efforts should focus on intervening with women at high risk of not receiving adjuvant radiotherapy and increasing rates of radiotherapy completion.