RESUMEN
BACKGROUND: Docetaxel and gemcitabine are active against breast cancer. The purpose of this phase II study was to evaluate the efficacy and safety of monthly docetaxel combined with weekly gemcitabine in patients with chemotherapy-pretreated metastatic breast cancer. PATIENTS AND METHODS: Thirty-nine patients were enrolled, of whom thirty had received prior chemotherapy in the adjuvant setting, seven for metastatic disease, and two for both, including prior anthracycline in 33 patients. Treatment was gemcitabine 800 mg/m2 days 1, 8, 15 and docetaxel 100 mg/M2 on day 1, with cycles repeated every four weeks. RESULTS: Response rate was 79% (95% confidence interval (CI): 63%-91%), with 2 complete and 29 partial responses. Twenty-five of the responders remained progression-free for more than six months. Median survival was 24.5 months. Delivered dose intensity of gemcitabine was lower than expected (63% of planned). The predominant hematologic toxicity was grade 4 neutropenia in 36 patients, complicated by fever in three patients. With the exception of asthenia, severe non-hematological toxicities were infrequent. CONCLUSIONS: Monthly docetaxel, combined with weekly gemcitabine, has significant but manageable hematologic toxicity. Despite frequent dose adjustments, this doublet is very active in metastatic breast cancer, producing a high proportion of durable responses associated with favorable survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Paclitaxel/análogos & derivados , Taxoides , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Docetaxel , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: Paraneoplastic pemphigus is a newly described autoimmune disease characterized by painful mucosal ulcerations and polymorphous skin lesions in association with an underlying neoplasm. All reported patients with an associated malignant neoplasm have had a poor prognosis. OBJECTIVE: We present three new cases of paraneoplastic pemphigus associated with a malignant neoplasm and further characterize this disease. METHODS: We used clinical criteria, histologic and immunopathologic examinations, and immunophenotyping to characterize this disease. In addition, we performed immunoprecipitation studies with extracts of radiolabeled human keratinocytes to characterize the antigens to which patient serum binds. RESULTS: All three patients had clinical, histologic, and immunopathologic findings that were strongly suggestive of paraneoplastic pemphigus. Their sera immunoprecipitated a complex of four polypeptides from human keratinocyte extracts with molecular weights of 250, 230, 210, and 190 kd, confirming the diagnosis of paraneoplastic pemphigus. The 250, 230, and 210 kd antigens comigrated with desmoplakin I, the 230 kd bullous pemphigoid antigen, and desmoplakin II, respectively. Lymphocyte immunophenotyping revealed large populations of monoclonal CD19+, CD5+ B cells in two cases. Although two of the patients died, one patient is alive and well 2 years after the diagnosis of paraneoplastic pemphigus. CONCLUSION: We report three cases of paraneoplastic pemphigus. One patient is alive and well 2 years after diagnosis, which suggests that a subgroup of patients may have a more benign course.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/patología , Linfoma no Hodgkin/patología , Enfermedades de la Boca/patología , Síndromes Paraneoplásicos/patología , Pénfigo/patología , Anciano , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Pruebas de Precipitina , Pronóstico , Estomatitis/patología , Enfermedades de la Lengua/patologíaRESUMEN
44 eligible patients with measurable or evaluable metastatic prostate cancer were treated with monthly cycles of cisplatin and mitoxantrone. Good-risk patients received cisplatin 60 mg/m2 intravenously and mitoxantrone 10 mg/m2 intravenously every 4 weeks. The dose in poor-risk patients (elderly or white blood cell count less than 4000/microliters, 4 x 10(9)/l, or extensive prior radiation) was reduced to 8 mg/m2. Toxicity was manageable and consisted primarily of myelosuppression. There were no complete responses and the partial response rate was only 12%. Median progression-free survival was 2.7 months for measurable and 4.1 months for evaluable disease patients. Median survivals were 4.9 and 8.7 months, respectively. This combination has minimal activity in hormone refractory metastatic prostate cancer.