Cardioprotective effect of dexrazoxane in patients with breast cancer treated with anthracyclines in adjuvant setting: a 10-year single institution experience.

BACKGROUND AND OBJECTIVE: Anthracyclines are highly effective and widely used cytotoxic agents, but their application is often limited by cumulative dose-dependent cardiotoxicity. Dexrazoxane has been shown in several clinical trials to prevent the development of this serious toxicity. The aim of our study was to analyze the incidence of cardiac dysfunction over a 10-year period in patients with breast cancer who were treated with anthracycline-based regimens with addition of dexrazoxane, mainly in an adjuvant setting. METHODS: We conducted a retrospective analysis on a population of women with breast cancer treated at our institution between January 1993 and October 2003. We reviewed patients' medical records and data on patient characteristics, treatment history, and adverse events that were collected, starting from the time of first visit before starting therapy, with the use of software created and designed for clinical records management in our institution (1999 OK-DH). Patients underwent an ECG assessment prior to starting chemotherapy, and were clinically monitored for cardiac failure. Those who developed signs and symptoms suggestive of cardiac dysfunction underwent further ECG. If clinical findings indicated, echocardiography and further cardiologic investigations were performed. The main outcome measure was the development of signs and symptoms indicative of congestive heart failure (CHF). RESULTS: A total of 318 female patients were treated with an anthracycline (doxorubicin or epirubicin)-based combination chemotherapy regimen during this time, in most cases in the adjuvant setting (n = 285). Most patients (n = 302) had early-stage disease and only 16 women presented with metastatic disease with good life expectancy (at least 1 year). All patients received dexrazoxane 1000 mg/m(2) intravenously prior to anthracycline administration during each chemotherapy cycle. The median follow-up duration was 35 months. During this time, five patients (1.57%) developed signs and symptoms of CHF. No patient at our institution died of heart failure during the period analyzed. Dexrazoxane was well tolerated, with no reports of adverse events associated with this drug. CONCLUSIONS: The reported incidence of cardiotoxicity in this study represents a marked reduction compared with historical data for patients receiving anthracycline-based chemotherapy without dexrazoxane. Dexrazoxane appears to have a cardioprotective effect in women with early-stage or advanced breast cancer treated with anthracycline-based combination chemotherapy, mainly as an adjuvant treatment. Prospective, randomized, controlled clinical trials in adjuvant setting should be performed to confirm these results.

Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.

PURPOSE: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. PATIENTS AND METHODS: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. RESULTS: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. CONCLUSIONS: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.