Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004093 (asthenia)
 2,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective observational study was conducted on patients diagnosed with serine/threonine-protein kinase B-Raf (BRAF)-mutated metastatic melanoma, who underwent first-line therapy with BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors (vemurafenib, dabrafenib or a combination of dabrafenib and trametinib) at the Miguel Servet University Hospital (Zaragoza, Spain) between November, 2011 and August, 2015. The aim of this study was to analyse the toxicity produced by BRAF and MEK inhibitors. The most common toxicities were similar to those published in clinical trials, particularly arthralgia, alopecia and photosensitivity in the vemurafenib group; asthenia, hyperkeratosis and dry skin in the dabrafenib group; and diarrhoea and dry skin in the dabrafenib plus trametinib group. Toxicities that had not been described in clinical trials were also identified. Thus, the present study confirmed that the results obtained in clinical trials are similar to those obtained in clinical practice.
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PMID:Comparative safety of BRAF and MEK inhibitors (vemurafenib, dabrafenib and trametinib) in first-line therapy for BRAF-mutated metastatic melanoma. 2769 43

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.
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PMID:Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study. 2938 60