Multi-Institutional Phase II Study of Selumetinib in Patients With Metastatic Biliary Cancers
| العنوان: | Multi-Institutional Phase II Study of Selumetinib in Patients With Metastatic Biliary Cancers |
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| المؤلفون: | William L. Marsh, Stephanie M. Balsom, Laura W. Goff, Mark Bloomston, Ryan Liersemann, Catherine Balint, L. Austin Doyle, Bert H. O'Neil, Vasily Vasko, Motoyasu Saji, John S. Kauh, Mitch A. Phelps, Miguel A. Villalona-Calero, Tanios Bekaii-Saab, Michael R. Grever, Matthew D. Ringel, Xiaobai Li, Gilian Ellison |
| المصدر: | Journal of Clinical Oncology. 29:2357-2363 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Proto-Oncogene Proteins B-raf, Oncology, MAPK/ERK pathway, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, MAP Kinase Kinase 2, MAP Kinase Kinase 1, Phases of clinical research, Proto-Oncogene Proteins p21(ras), Proto-Oncogene Proteins, Internal medicine, Original Reports, Clinical endpoint, Humans, Medicine, Neoplasm Metastasis, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Protein kinase B, Aged, Mitogen-Activated Protein Kinase Kinases, business.industry, Liver Neoplasms, Middle Aged, Clinical trial, Biliary Tract Neoplasms, Mutation, ras Proteins, Cancer research, Selumetinib, Immunohistochemistry, Benzimidazoles, Female, business, Proto-Oncogene Proteins c-akt |
| الوصف: | Purpose Biliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is of significance. Selumetinib is an inhibitor of MEK1/2, so this trial was designed to determine the safety and efficacy of selumetinib in BC. Patients and Methods This was a multi-institutional phase II study of selumetinib at 100 mg given orally twice per day to patients with advanced BC. The primary end point was response rate. All patients were required to provide tissue before enrolling. The levels of phosphorylated ERK (pERK) and AKT (pAKT) were assessed by immunohistochemistry. Tumors were genotyped for the presence of BRAF- and/or RAS-activating mutations. Results Twenty-eight eligible patients with a median age of 55.6 years were enrolled. Thirty-nine percent of patients had received one prior systemic therapy. Three patients (12%) had a confirmed objective response. Another 17 patients (68%) experienced stable disease (SD), 14 of whom (56%) experienced prolonged SD (> 16 weeks). Patients gained an average nonfluid weight of 8.6 pounds. Median progression-free survival was 3.7 months (95% CI, 3.5 to 4.9) and median overall survival was 9.8 months (95% CI, 5.97 to not available). Toxicities were mild, with rash (90%) and xerostomia (54%) being most frequent. Only one patient experienced grade 4 toxicity (fatigue). All patients had tissue available for analysis. No BRAF V600E mutations were found. Two patients with short-lived SD had KRAS mutations. Absence of pERK staining was associated with lack of response. Conclusion Selumetinib displays interesting activity and acceptable tolerability in patients with metastatic BC. Our results warrant further evaluation of selumetinib in patients with metastatic BC. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ebdf3196064b4bfcb470a440a73c8466Test https://doi.org/10.1200/jco.2010.33.9473Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ebdf3196064b4bfcb470a440a73c8466 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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