RESUMEN
BACKGROUND: Enzalutamide is a second-generation androgen receptor (AR) inhibitor that binds to and blocks the AR with higher affinity than previously available AR inhibitors. High activity has been proven in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and in chemotherapy-naive patients with mCRPC. However, its activity in patients previously treated with other novel agents (for example, abiraterone and/or cabazitaxel), remains controversial. PATIENTS AND METHODS: The aim of this retrospective analysis of the Swiss Enzalutamide Named Patient Program was to evaluate clinical efficacy and safety of enzalutamide treatment in patients with mCRPC progressing after docetaxel and other lines of therapy considering different treatment sequences. We report on 44 patients treated with enzalutamide. RESULTS: The median survival time from diagnosis of CPRC was 41.1 months (95% confidence interval [CI], 32.3-49.8 months). Enzalutamide was used as a second, third, fourth, fifth, sixth, or seventh-line therapy in 13%, 20%, 31%, 20%, 11%, and 2% of patients. The median duration of enzalutamide treatment was 3.0 months (range, 1-21 months). Median progression-free survival was 3.0 months (95% CI, 2.4-3.7 months). The estimated median overall survival was 6.3 months (95% CI, 4.6-8.1 months). Sixteen patients (36.4%) had a prostate-specific antigen decrease of ≥ 30%, and 11 patients (25.0%) of ≥ 50%, respectively. In multivariate analysis, the absence of previous therapy with abiraterone and a prostate-specific antigen response of ≥ 50% on enzalutamide therapy were significantly associated with overall survival on enzalutamide treatment. CONCLUSIONS: Our results show that enzalutamide has modest activity in extensively pretreated patients. However, there is a subgroup of patients achieving benefit from enzalutamide therapy even after pretreatment with abiraterone.
Asunto(s)
Antineoplásicos/administración & dosificación , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Antineoplásicos/uso terapéutico , Benzamidas , Docetaxel , Humanos , Masculino , Nitrilos , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/uso terapéutico , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Taxoides/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin. PATIENTS AND METHODS: An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar's matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%. RESULTS: Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events. CONCLUSION: Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer.
Asunto(s)
Hidróxido de Aluminio , Neoplasias de la Mama , Cloruros , Doxorrubicina/análogos & derivados , Síndrome Mano-Pie/prevención & control , Administración Tópica , Anciano , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/uso terapéutico , Antitranspirantes/farmacología , Antitranspirantes/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Cloruros/farmacología , Cloruros/uso terapéutico , Método Doble Ciego , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Monitoreo de Drogas/métodos , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Índice de Severidad de la Enfermedad , Crema para la Piel , Resultado del TratamientoRESUMEN
BACKGROUND: Trastuzumab is an established treatment for HER2-positive breast cancer (BC). We analyzed Swiss patterns of care in patients with HER2-positive BC after disease progression on trastuzumab-containing therapy for metastatic BC (MBC). PATIENTS AND METHODS: A retrospective analysis was performed in six Swiss BC centers. Patients with HER2-positive MBC treated with at least one infusion of trastuzumab for advanced disease between January 2006 and December 2007 were identified. Treatment patterns in first and further lines were analyzed. RESULTS: All of the 72 identified patients received trastuzumab as their first palliative anti-HER2 therapy, either as monotherapy (n = 23) or in combination with chemotherapy (typically taxane or vinorelbine; n = 49). Median time to progression was 8.1, 8.0 and 7.9 months in the monotherapy, trastuzumab-taxane and trastuzumab-vinorelbine cohorts, respectively. After progression on first-line anti-HER2 therapy, trastuzumab was continued in 67 of 68 patients who received further therapy. One patient received second-line lapatinib plus capecitabine. The median duration of anti-HER2 therapy was 20 months. Patients received a median of 4 lines of anti-HER2 therapy. CONCLUSIONS: Durable responses were achieved with repeated exposure to anti-HER2 therapy. In a selected patient population, trastuzumab monotherapy appears to be a reasonable first-line treatment option.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/enzimología , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Suiza , Taxoides/administración & dosificación , Trastuzumab , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
BACKGROUND: Bleomycin is an antineoplastic agent that is mainly used in combination regimens. Dose-limiting toxicity is the bleomycin-induced pneumonitis (BIP) that can be diagnosed by clinical and radiological findings. The early diagnosis of BIP is often challenging. CASE REPORT: We report the occurrence of a diffuse pulmonary increase of FDG uptake in the FDG-PET scan in association with suspected BIP in a patient treated for relapsed seminoma. A retroperitoneal relapse was treated with a combination chemotherapy containing cisplatin, etoposide, and bleomycin. After 3 cycles of this regimen the patient developed mild clinical signs of early BIP. A following FDG-PET in order to evaluate treatment response showed a diffuse increased FDG uptake of the right lung. The subsequent HRCT revealed pathological findings consistent with BIP. After cessation of bleomycin and a systemic steroid trial a prompt normalization of the abnormal radiological and clinical findings occurred together with a disappearance of the increased pulmonary FDG uptake. CONCLUSION: FDG-PET can be used for evaluation of residual disease in patients treated for advanced seminoma. In cases of otherwise unexplained increased pulmonary FDG uptake in patients under treatment with bleomycin an evaluation for early BIP as a possible cause of this finding is warranted.