مورد إلكتروني
Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer.
| العنوان: | Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer. |
|---|---|
| المؤلفون: | Gross, Neil D |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research; vol 20, iss 12, 3289-3298; 1078-0432 |
| بيانات النشر: | eScholarship, University of California 2014-06-01 |
| تفاصيل مُضافة: | Gross, Neil D Bauman, Julie E Gooding, William E Denq, William Thomas, Sufi M Wang, Lin Chiosea, Simion Hood, Brian L Flint, Melanie S Sun, Mai Conrads, Thomas P Ferris, Robert L Johnson, Jonas T Kim, Seungwon Argiris, Athanassios Wirth, Lori Nikiforova, Marina N Siegfried, Jill M Grandis, Jennifer R |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | PurposeThe EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo.Experimental designPatients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib-sulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. The primary endpoint was change in Ki67 proliferation index. We hypothesized an ordering effect in Ki67 reduction: erlotinib-sulindac > erlotinib > placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling intermediates.ResultsFrom 2005-2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or erlotinib-sulindac (omnibus comparison, two-sided Kruskal-Wallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinib-sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib-sulindac > erlotinib > placebo (two-sided exact Jonckheere-Terpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R(2) = 0.312, P = 0.024).ConclusionsBrief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target. |
| مصطلحات الفهرس: | Humans, Carcinoma, Squamous Cell, Head and Neck Neoplasms, Quinazolines, Sulindac, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Staging, Immunoenzyme Techniques, Prognosis, Tissue Array Analysis, Cohort Studies, Follow-Up Studies, Double-Blind Method, Adult, Aged, 80 and over, Middle Aged, Female, Male, ErbB Receptors, Biomarkers, Tumor, Erlotinib Hydrochloride, Clinical Research, Rare Diseases, Cancer, Dental/Oral and Craniofacial Disease, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Oncology and Carcinogenesis, Oncology & Carcinogenesis, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf Clinical cancer research : an official journal of the American Association for Cancer Research vol 20, iss 12, 3289-3298 1078-0432 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt8sd3958z qt8sd3958z https://escholarship.org/uc/item/8sd3958zTest https://escholarship.orgTest/ 1377974030 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1377974030 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |