RESUMEN
PURPOSE: To evaluate the safest timing of pegfilgrastim administration in dose-dense anthracycline- and taxane-based chemotherapy, three different cohorts of patients enrolled in the Gruppo Italiano Mammella (GIM) 2 study and treated at the coordinating center received pegfilgrastim 24 h (cohort A) or 72 h (cohort B) or 96 h (cohort C) after chemotherapy. METHODS: A total of 41 patients were included. The safety of pegfilgrastim administration in terms of occurrence of early and late leukocytosis and the behavior of white blood cells (WBC) counts in the three cohorts across all chemotherapy cycles were evaluated. Anthracycline and taxane cycles were analyzed separately. RESULTS: The occurrence of early leukocytosis was a more common event in patients in cohort A in both anthracycline and taxane cycles (75 and 66.7%) as compared to cohort B (50 and 60%) and cohort C (66.7 and 33.3%). More patients in cohort C developed late leukocytosis in both anthracycline and taxane cycles (50 and 100%) as compared to cohort A (0 and 66.7%) and cohort B (35.7 and 86.7%). Patients in cohort A experienced the highest median value of WBC count 24 h after pegfilgrastim administration in both anthracycline and taxane cycles (61.2 × 10(3)/µl and 67.8 × 10(3)/µl). Patients in cohort C experienced the highest median value of WBC count at day 13 in both anthracycline and taxane cycles (19.4 × 10(3)/µl and 24.2 × 10(3)/µl). CONCLUSIONS: For the prevention of leukocytosis, the safest timing of pegfilgrastim administration based on WBC count in dose-dense anthracycline- and taxane-based regimens seems to be 72 h after chemotherapy. TRIAL REGISTRATION: This study is registered with https://clinicaltrials.gov/ct2/show/NCT00433420.
Asunto(s)
Antraciclinas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Taxoides/uso terapéutico , Adulto , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Estudios de Cohortes , Esquema de Medicación , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Italia , Persona de Mediana Edad , Polietilenglicoles , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Factores de TiempoAsunto(s)
Linfoma no Hodgkin/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/efectos adversos , Compuestos de Mostaza Nitrogenada/uso terapéutico , Síndrome de Stevens-Johnson/inducido químicamente , Anciano , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/uso terapéutico , Clorhidrato de Bendamustina , Femenino , Hepatitis C/complicaciones , Humanos , Linfoma no Hodgkin/complicaciones , Síndrome de Stevens-Johnson/complicaciones , Síndrome de Stevens-Johnson/diagnósticoRESUMEN
PURPOSE: The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics. METHODS: We evaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing. RESULTS: We demonstrated the direct statistical correlation between the level of methylation of all HOXA genes examined and WHO grading. Moreover, in glioblastoma patients, higher level of HOXA9 and HOXA10 methylation significantly correlated with increased survival probability (HOXA9-HR: 0.36, P = 0.007; HOXA10-HR: 0.46, P = 0.045; combined HOXA9 and 10-HR 0.28, P = 0.004). CONCLUSIONS: This study identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma patients. Our data indicate that these epigenetic changes may be biomarkers of clinically different subgroups of glioma patients that could eventually benefit from personalized therapeutic strategies.
Asunto(s)
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Metilación de ADN , Glioma/genética , Glioma/patología , Proteínas de Homeodominio/genética , Neoplasias Encefálicas/metabolismo , Cromosomas Humanos Par 7 , Análisis por Conglomerados , Amplificación de Genes , Glioma/metabolismo , Proteínas Homeobox A10 , Proteínas de Homeodominio/biosíntesis , Humanos , Clasificación del Tumor , Tasa de SupervivenciaRESUMEN
BACKGROUND: The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen. METHODS: Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P = .86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P = .76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P = .36). CONCLUSIONS: No statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo- and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo- and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these results must be considered with caution.
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Antineoplásicos Hormonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Axila , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Factores de Confusión Epidemiológicos , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Epirrubicina/administración & dosificación , Epirrubicina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Glucuronatos/administración & dosificación , Humanos , Italia , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Mastectomía Segmentaria , Metotrexato/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Pronóstico , Modelos de Riesgos Proporcionales , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Factores de Riesgo , Tamoxifeno/administración & dosificación , Resultado del TratamientoRESUMEN
Angiosarcoma of the breast is a malignant tumour of vascular endothelial cells. It is a rare and difficult tumour to treat. The authors report a case of cutaneous radiation-associated angiosarcoma treated with paclitaxel chemotherapy. A few days after drug administration, bleeding of skin lesions was observed and the patient died.
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Neoplasias de la Mama/inducido químicamente , Hemangiosarcoma/inducido químicamente , Neoplasias Primarias Secundarias/inducido químicamente , Paclitaxel/efectos adversos , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/patología , Femenino , Hemangiosarcoma/patología , Humanos , Neoplasias Primarias Secundarias/patología , Paclitaxel/uso terapéuticoRESUMEN
Sixty-eight patients with inflammatory breast carcinoma (IBC) received treatment in 2 prospective randomized trials of multimodality therapy for locally advanced breast cancer. The treatment plan consisted of 3 courses of neoadjuvant chemotherapy with CAF (cyclophosphamide/doxorubicin/5-fluorouracil [5-FU]) or CEF (cyclophosphamide/epirubicin/5-FU) followed by surgery and 6 adjuvant courses of CAF or CEF alternated with CMF (cyclophosphamide/methotrexate/5-FU). Radiation therapy was administered at the end of adjuvant treatment. All patients with estrogen receptor-positive tumors received tamoxifen 20 mg daily for 5 years. The response rate to induction chemotherapy was 73.6% (95% CI, 61.4%-83.5%): 4 of 68 patients (6%) exhibited a pathologic remission of primary breast tumor (persistent disease in the axilla), and 2 patients (3%) exhibited a pathologic complete response. Median follow-up was 10 years (range, 5 months to 14.7 years). Disease-free survival (DFS) rates at 5 and 10 years were 29% and 20%, respectively, and median DFS was 2.2 years (range, 3.8 months to 11.5 years). Overall survival (OS) rates at 5 and 10 years were 44% and 32%, respectively, and median OS was 4 years (range, 5 months to 14.7 years). Significant prognostic factors for DFS and OS were the number of axillary nodes and residual disease in the breast at surgery. This analysis confirmed that patients with IBC obtained significant long-term survival benefit from combined-modality therapy.