Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation.

AIM: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). METHODS: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary end-points were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations. RESULTS: Of 481 patients randomised (242 placebo-paclitaxel; 239 bevacizumab-paclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51-0.91; log-rank p = 0.0007) in the intent-to-treat population (median 8.8 months with placebo-paclitaxel versus 11.0 months with bevacizumab-paclitaxel) and 0.64 (96% confidence interval, 0.47-0.88; log-rank p = 0.0038) in the pVEGF-Ahigh subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade ≥3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade ≥3: 11% versus 4%). CONCLUSION: The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01663727.

Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix.

PURPOSE: To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer. PATIENTS AND METHODS: Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A). RESULTS: Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A. CONCLUSION: Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a malignant neoplasia of the salivary glands that is treated primarily by surgery. Local control and survival are usually compromised despite surgery. Expression of KIT tyrosine kinase is involved in the pathogenesis of ACC. Imatinib mesylate is a potent inhibitor of KIT tyrosine kinase, so we explored the possibility that ACC could be a potential target for this drug. METHODS: We report two cases of unresectable ACC treated with imatinib mesylate in the context of recurrent disease (case 1) and locally advanced tumor at its initial presentation (case 2). RESULTS: Both patients responded well to treatment with imatinib mesylate. Significant regression of recurrent disease (case 1) resulted in a successful salvage surgical resection; the locally advanced tumor (case 2) had an excellent response to treatment, but, unfortunately, the patient refused salvage resection. CONCLUSION: This is the first time ACC is reported to respond to imatinib mesylate. Studies in which more patients are enrolled in controlled clinical trials are needed to confirm this observation.

Informe del primer caso de insuficiencia renal aguda por picaduras de abejas africanizadas con requerimientos de hemodialisis en el complejo Hospitalario Metripolitano de la Caja de Seguro Social / Firts case report of kidney failure acute for africanized bees with hemodialysis request in the Complejo Hospitalario Metropolitano de la Caja de Seguro Social

Se presenta el caso de un paciente del sexo masculino, de 46 años de edad, quién sufrió múltiples picaduras por abejas africanizadas en diversas partes del cuerpo que le produjeron vómitos, mialgias generalizadas, oliguria progresiva y trastornos en la coagulación por lo que desarrolló una insuficiencia renal aguda anúrica que requirió 21 sesiones de hemodiálisis antes de que pudiera superar la crisis. Presentó una creatinina máxima de 13.3 mg/dL que a su egreso ya había disminuido a 4.3 mg/dL (INV.)

Cisplatino y vinorelbina en cáncer avanzado de células no pequeñas de pulmón. Experiencia en el Instituto Nacional de Cancerología / Treatment with cisplatin and vinorelbine in advanced no-small cell lung carcinoma

Para determinar la eficacia y seguridad de un régimen de quimioterapia a base de cisplatino y vinorelbina con o sin radioterapia en cáncer de células no pequeñas de pulmón, revisamos retrospectivamente 16 expedientes clínicos (nueve hombres y siete mujeres; edad media de 53 años; dos en etapa clínica IIIA, 11 en IIIB y tres en IV). Distinguimos tres modalidades de tratamiento: quimioterapia sola (cinco casos), quimioterapia y radioterapia concomitantes (dos pacientes) y quimioterapia de induccción seguida de quimioterapia y radioterapia concomitantes (nueve enfermos). La respuesta global fue 68.7 por ciento (18.7 por ciento completas y 50 por ciento parciales). La mediana de supervivencia global fue 13 meses y la de supervivencia libre de progresión 12 meses. La tasa de supervivencia a un año fue 75 por ciento. Se observó una tendencia a mayor supervivencia global, supervivencia libre de progresión, respuestas globales y supervivencia a un año en quienes recibieron alguna modalidad de radioterapia agregada. La toxicicdad grado 3-4 se distribuyó así hematológica (neutropenia) en seis pacientes, ninguno de los cuales requirió hospitalización ni antibióticos; y no hematológica (náuses y vómitos) en siete enfermos. Hubo neuropatía periférica grado 1-2 en cinco sujetos. No observamos mayor toxicidad asociada a tratamiento combinados. Cisplatino y vinorelbina con o sin radioterapia es un régimen eficaz y bien tolerado