التفاصيل البيبلوغرافية
| العنوان: |
Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial |
| المؤلفون: |
Tianxiang Lin, Randal C. Paniello, Tanya M. Wildes, Farrokh Dehdashti, James S. Lewis, Jonathan H. Law, Gavin P. Dunn, Barry A. Siegel, Jason T. Rich, L. Michel, Ashley E. Winkler, Paul Zolkind, Bruce H. Haughey, Rebecca D. Chernock, Jay F. Piccirillo, Ravindra Uppaluri, Dorina Kallogjeri, Brian Nussenbaum, Jason Diaz, Douglas Adkins |
| المصدر: |
Clinical cancer research : an official journal of the American Association for Cancer Research. 23(9) |
| سنة النشر: |
2016 |
| مصطلحات موضوعية: |
0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, MAP Kinase Signaling System, Pyridones, medicine.medical_treatment, Pyrimidinones, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Carcinoma, Biomarkers, Tumor, Humans, Oral Cavity Squamous Cell Carcinoma, Protein Kinase Inhibitors, Neoadjuvant therapy, Aged, Neoplasm Staging, Trametinib, Mouth, business.industry, Cancer, Middle Aged, medicine.disease, Primary tumor, Neoadjuvant Therapy, Surgery, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Hyaluronan Receptors, Oncology, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Carcinoma, Squamous Cell, Biomarker (medicine), Female, Mouth Neoplasms, business |
| الوصف: |
Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib. Experimental Design: Patients with stage II–IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUVmax) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated. Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related (n = 2: nausea, duodenal perforation) or unrelated (n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%–74%). Partial metabolic response (≥25% reduction in SUVmax) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%–52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients. Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186–94. ©2016 AACR. |
| تدمد: |
1557-3265 |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a56d023f053a709c68a0f2efb7f7b04Test
https://pubmed.ncbi.nlm.nih.gov/28151720Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....6a56d023f053a709c68a0f2efb7f7b04 |
| قاعدة البيانات: |
OpenAIRE |
