RESUMEN
BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%). PATIENTS AND METHODS: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. IMPLICATIONS FOR PRACTICE: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis.
Asunto(s)
Androstadienos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Everolimus/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Androstadienos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Everolimus/efectos adversos , Femenino , Humanos , Italia , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
PURPOSE Comprehensive geriatric assessment (CGA) is a multidimensional method used by geriatricians and oncologists to detect and evaluate multiple age-related problems and to plan and coordinate interventions. Because its main drawback is the time required, efforts have been made to evaluate screening instruments suitable for preliminarily assessing elderly patients. The main aim of this study was to establish the accuracy of the Vulnerable Elders Survey-13 (VES-13) in predicting the presence of abnormalities revealed by CGA. PATIENTS AND METHODS Patients age > or = 70 years with a histologically or cytologically confirmed diagnosis of a solid or hematologic tumor underwent both CGA and a VES-13 assessment, and the reliability and validity of VES-13 were analyzed. Results Fifty-three percent of the 419 elderly patients with cancer (mean age, 76.8 years) were vulnerable on VES-13; the rates of disabilities on CGA and activities of daily living (ADLs)/instrumental activities of daily living (IADLs) scales were 30% and 25%, respectively. The sensitivity and specificity of VES-13 were 87% and 62%, respectively, versus CGA and 90% and 70%, respectively, versus ADL/IADL scales. CONCLUSIONS On the basis of our data, VES-13 is highly predictive of impaired functional status and can thus be considered a useful preliminary means of assessing older patients with cancer before undertaking a full CGA.
Asunto(s)
Actividades Cotidianas , Evaluación de la Discapacidad , Evaluación Geriátrica , Servicios de Salud para Ancianos , Neoplasias/diagnóstico , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Encuestas de Atención de la Salud , Humanos , Italia/epidemiología , Masculino , Neoplasias/fisiopatología , Neoplasias/psicología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Fulvestrant ('Faslodex') is an oestrogen receptor (ER) antagonist with no agonist effects. The drug was administered to heavily pre-treated patients with advanced breast cancer (ABC). Patients received Fulvestrant after disease progression (PD) on a previous endocrine treatment or as maintenance treatment after chemotherapy. MATERIAL AND METHODS: Fifty-seven postmenopausal women with ER and/or progesterone receptor-positive ABC resistant to previous endocrine treatments prospectively received fulvestrant 250 mg via intramuscular injection q 28. RESULTS: Twenty-seven patients received fulvestrant after PD and 30 received it as maintenance therapy after chemotherapy. All patients received fulvestrant as second-up to eight-line endocrine treatment for ABC. One patient (2%) had a partial response (PR) and 24 patients (42%) had stable disease > or =12 weeks (SD), including 11 patients who had SD > or =24 weeks. Thirty-two patients (56%) had de novo PD. Clinical benefit (CB; PR + SD > or =24 weeks) occurred in 12 patients (21%). Patients treated as maintenance and treated upon PD had 0 and 4% PR, 43 and 41% SD (including 20 and 19% SD > or =24 weeks), 57 and 55% PD, respectively. Overall, median time to progression (TTP) was 3 months. No differences in CB rate (20% vs. 23%), TTP (3 months vs. 3 months) and time to treatment failure (3 months vs. 3 months) were observed between patients receiving fulvestrant as maintenance therapy and those treated at PD on prior endocrine treatment. No grade 2-4 NCI-CTC toxicity was recorded. CONCLUSIONS: Fulvestrant treatment was associated with prolonged CB and was well tolerated in this group of heavily pre-treated patients with ABC. The outcomes appeared to be similar for patients treated upon PD and those receiving fulvestrant as maintenance therapy.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Empatía , Estradiol/análogos & derivados , Antagonistas de Estrógenos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Estradiol/administración & dosificación , Estradiol/efectos adversos , Estradiol/uso terapéutico , Antagonistas de Estrógenos/administración & dosificación , Antagonistas de Estrógenos/efectos adversos , Femenino , Fulvestrant , Humanos , Inyecciones Intramusculares , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Receptores de Estrógenos/análisis , Receptores de Estrógenos/antagonistas & inhibidores , Receptores de Progesterona/análisis , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The combination of capecitabine and vinorelbine is a potentially valuable treatment regimen for patients with advanced-stage breast cancer. The drugs are easy to administer and do not cause significant alopecia. In order to identify the spectrum of toxicity of a regimen containing 2 drugs, we conducted an extended phase I study aimed at defining maximum tolerated doses, recommended doses, safety, and efficacy in patients with pretreated advanced-stage breast cancer. PATIENTS AND METHODS: Forty-nine patients with advanced-stage breast cancer were treated with escalating doses of oral capecitabine from 500 mg/m2 to 1375 mg/m2 twice daily on days 1-14 and escalating doses of vinorelbine from 12.5 mg/m2 to 25 mg/m2 intravenously (I.V.) on days 1 and 3 every 3 weeks. Almost all patients (90%) had received >or= 3 previous treatments for metastatic disease (anthracyclines, 76%; 5-flourouracil, 76%; taxanes, 29%). RESULTS: Dose level 9 (capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3) was identified as the maximum tolerated dose. The most frequent clinical adverse events were nausea (78%), asthenia (59%), constipation (51%), mucositis (47%), and hand-foot syndrome (41%). The majority of events were mild to moderate; the only grade 4 clinical adverse events were diarrhea, fever, and thromboembolism, each of which occurred in 1 patient (2%) at dose level 8. Objective confirmed responses were observed in 18 patients (37%), including 1 complete response (2%) and 17 partial responses (35%). Disease was stable in an additional 10 patients (20%), with a median duration of 6.3 months (range, 4-24 months). CONCLUSION: The combination of the 2 drugs is very well tolerated and effective, especially considering the previous exposure to chemotherapy. The recommended dose for further phase II studies should be capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3.