Common envelope binary interaction simulations between a thermally pulsating AGB star and a low mass companion.

At least one in five of all planetary nebulae are the product of a common envelope (CE) interaction, where the companion in-spirals into the envelope of an asymptotic giant branch (AGB) star ejecting the nebula and leaving behind a compact binary. In this work we carry out 3D smoothed particle hydrodynamics simulations of the CE interaction between a 1.7 M AGB star and a 0.

Comparative Bioavailability of a Single Dose of Trametinib (TMT212) Containing 9% vs 11% Dimethyl Sulfoxide in Randomized Healthy Volunteers to Assess Long-Term Storage at Room Temperature.

Storage of trametinib tablets outside of 2-8°C protected from moisture may lead to loss of dimethyl sulfoxide (DMSO) and adversely impact trametinib bioavailability. In this open-label, phase 1, single-dose, randomized, 2-treatment, 2-period crossover study in healthy volunteers, bioavailability of a single 2-mg tablet of trametinib containing 9% DMSO (test formulation), corresponding to the lowest DMSO content in the tablet after storage at 25°C for 36 months, was evaluated vs bioavailability of a 2-mg tablet containing 11% DMSO (reference formulation). Sixty-five percent of subjects (n = 39/65) were men, and mean (standard deviation) age was 45.

Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy.

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy ( NCT02231775 , n = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P = 0.001; RFS, 64% versus 32% at 2 years, P = 0.

Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event management algorithm in patients treated with adjuvant dabrafenib plus trametinib: Primary results of COMBI-APlus.

Background: COMBI-AD demonstrated long-term benefit of adjuvant dabrafenib plus trametinib in patients with resected stage III BRAF V600E/K-mutant melanoma; however, 9% of patients permanently discontinued therapy due to pyrexia. COMBI-APlus evaluated whether an adapted pyrexia management algorithm reduces high-grade pyrexia and pyrexia-related adverse outcomes.

Methods: COMBI-APlus is an open-label, phase IIIb trial evaluating an adapted pyrexia management algorithm in patients with high-risk resected stage III BRAF V600E/K-mutant melanoma treated with up to 12 months of adjuvant dabrafenib plus trametinib.

Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers.

Background: Dabrafenib plus trametinib has demonstrated clinical benefit across multiple BRAF-mutant tumours, leading to approval for resected stage III and metastatic melanoma, non-small-cell lung cancer (NSCLC) and anaplastic thyroid cancer. Pyrexia is a common adverse event in patients treated with dabrafenib plus trametinib. Here, we characterise the incidence, patterns and management of pyrexia in patients receiving dabrafenib plus trametinib in clinical trials.

Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II).

In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted.

Effectiveness of dabrafenib in the treatment of patients with BRAF V600-mutated metastatic melanoma in a Named Patient Program.

Given the approval of dabrafenib in patients with BRAF-mutant metastatic melanoma, a better understanding of treatment patterns and clinical outcomes with dabrafenib in a clinical setting is warranted. We performed a retrospective chart review of patients who received dabrafenib in a compassionate use setting through the Named Patient Program (DESCRIBE I study) during December 2010-August 2013 in Europe, New Zealand and Australia. Of the 331 Named Patient Program patients included, the majority (95.

Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer.

Background: Brain metastases are common in human epidermal growth factor receptor (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain is key to management of cranial disease. In this study, positron emission tomography (PET) scanning after administration of radiolabelled lapatinib was used to obtain direct evidence of cranial drug access.

Phase I Study of Lapatinib and Pemetrexed in the Second-Line Treatment of Advanced or Metastatic Non-Small-Cell Lung Cancer With Assessment of Circulating Cell Free Thymidylate Synthase RNA as a Potential Biomarker.

Introduction: Lapatinib is a dual tyrosine kinase inhibitor that targets epidermal growth factor receptor and HER2. We report on a dose-escalation study of lapatinib combined with pemetrexed in second-line treatment to evaluate the safety and efficacy in advanced or metastatic non-small-cell lung cancer (NSCLC) and an exploratory study in which circulating cell-free thymidylate synthase ribonucleic acid (cfTSmRNA) was measured in all patients and compared with clinical benefit.

Patients And Methods: Eligible patients had stage IIIB or IV NSCLC after 1 previous line of chemotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2.

Amplification of epidermal growth factor receptor gene in renal cell carcinoma.

Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2 patients (0.