Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer.

Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m2 onalespib when given with paclitaxel at 80 mg/m2. PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173.

Phase 1b study of HSP90 inhibitor called onalespib in combination with paclitaxel in patients with advanced triple-negative breast cancer This Phase 1b study demonstrated that treatment with a combination of onalespib and paclitaxel was reasonably well tolerated by most patients. Onalespib at 260 mg/m² given intravenously on days 1, 8 and 15 on 28-day cycles in combination with standard dose and schedule of paclitaxel was established as the recommended phase 2 dose for further clinical development. Despite minor drug-drug interactions between these 2 agents, onalespib did not alter paclitaxel exposure and paclitaxel did not affect exposure to onalespib. While onalespib with paclitaxel combination therapy did not yield durable objective responses or prolonged progression-free survival, there were several patients with long-lasting benefit from this combination including patients who previously experienced progression on taxane therapy.

Respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.

BACKGROUND: Morbidity and mortality related to respiratory syncytial virus (RSV) in pediatric acute myeloid leukemia (AML) is not known. PROCEDURE: We combined data from three Children's Oncology Group AML studies and determined the prevalence of RSV infection and RSV-related mortality in children treated for de novo AML. RESULTS: We found that the prevalence of RSV infection ranged from 0% to 1% in induction and between 0.3 and 2.2% in consolidation. Four children died from RSV resulting in RSV-specific mortality of 0.2% among all children. However, the risk of RSV-related mortality among RSV infection episodes was high (4/40, 10%). CONCLUSIONS: RSV infections and deaths are rare in pediatric AML.

Higiene bucal: su repercusión en pacientes con tratamientos ortodóncicos / Oral higiene: its impacto on patients with orthodontic treatment

El éxito de los tratamientos ortodóncicos aplicados en la adolescencia radica en mantener una higiene bucal buena, la cual favorece un buen funcionamiento y evita la aparición de complicaciones en los pacientes, asociado con un correcto cepillado de los dientes y de los aparatos ortodóncicos, lo que es un elemento esencial e importante para un tratamiento exitoso, unido al mantenimiento saludable de las encías, prevención de las caries y peridontitis. Se realizó un estudio descriptivo en 50 pacientes de uno u otro sexo y raza, con edades comprendidas entre 12-16 años, procedentes de la Consulta de Ortodoncia de la Clínica Estomatológica H y 21, en el período de marzo-agosto del 2006, los cuales reciben tratamiento ortodóncico, con el objetivo de determinar la higiene bucal durante el tratamiento. Predominó el sexo masculino y el grupo de 12-14 años. Se observó que el 92 por ciento de los pacientes estudiados se categorizó con índice de higiene bucal simplificado bueno y solo el 8 por ciento con un índice de higiene bucal simplificado regular. Finalmente el índice de higiene bucal simplificado del colectivo fue bueno. Se recomienda incrementar y fomentar aún más el mantenimiento de la higiene bucal, para obtener un buen éxito durante el tratamiento ortodóncico y por lo tanto, que el paciente pueda disfrutar de una bonita sonrisa sin afectaciones psicológica(AU)

The success of orthodontic treatment applied in adolescence lies in keeping a good oral hygiene, which favors good functioning of teeth and avoids the occurence of complications, associated to good brushing of teeth and of orthodontic appliances that is an eseential and important element for healthy conditon of gingivae, prevention of dental caries and peridontitis. A descriptive study of 50 patients of either sex and any race aged 12-16 years from Orthodontic Service of Dental Clinc H y 21 was conducted from March to August, 2006. They received orthodontic treatment to determine their oral hygiene in the course of treatment. It was observed that males and 12-14 y age group prevailed; 92 per cent and 8 per cent of patients were classified as having good and regular simplified oral hygiene index respectively. Finally, the index of the group was regarded as good. The study recommended to increase and foster oral hygiene to succeed in orthodontic treatment and thus the patient can enjoy a beatiful smile without psychological disorders(AU)