PHARMACODYNAMIC EVALUATION OF TEMSIROLIMUS IN PATIENTS WITH NEWLY DIAGNOSED ADVANCED-STAGE HEAD AND NECK SQUAMOUS CELL CARCINOMA

被引：25
作者：
Ekshyyan, Oleksandr [1 ,2 ]
Mills, Glenn M. [2 ]
Lian, Timothy [1 ,2 ]
Amirghahari, Nazanin [1 ,2 ]
Rong, Xiaohua [1 ,2 ]
Lowery-Nordberg, Mary [2 ]
Abreo, Fleurette [3 ]
Veillon, Diana M. [3 ]
Caldito, Gloria [4 ]
Speicher, Lisa [5 ]
Glass, Jonathan [2 ]
Nathan, Cherie-Ann O. [1 ,2 ]
机构：
[1] Louisiana State Univ, Hlth Sci Ctr, Dept Otolaryngol Head & Neck Surg, Shreveport, LA 71105 USA
[2] Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Shreveport, LA 71105 USA
[3] Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, Shreveport, LA 71105 USA
[4] Louisiana State Univ, Hlth Sci Ctr, Dept Biometry, Shreveport, LA 71105 USA
[5] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
来源：
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK | 2010年 / 32卷 / 12期
关键词：
temsirolimus; mTOR; squamous cell carcinoma; adjuvant therapy; head and neck cancer; MAMMALIAN TARGET; INTERFERON-ALPHA; RAPAMYCIN INHIBITORS; SURGICAL MARGINS; PTEN EXPRESSION; CANCER-PATIENTS; PHASE-II; CCI-779; PATHWAY; MTOR;
D O I：
10.1002/hed.21374
中图分类号：
R76 [耳鼻咽喉科学];
学科分类号：
100213 ;
摘要：
Background. Activation of the mammalian target of rapamycin (mTOR) pathway in surgical margins of head and neck squamous cell carcinoma (HNSCC) is a predictor of recurrence and patients with minimal residual disease may benefit from adjuvant therapy with temsirolimus, an mTOR inhibitor. Methods. The effects of 3 weekly doses of 25 mg of temsirolimus on Akt/mTOR pathway biomarkers were evaluated in tumor and peripheral blood mononuclear cells (PBMCs) of patients with HNSCC. Adverse events were assessed. Results. Temsirolimus significantly decreased pS6 and p4E-BP1 in tumors, and pS6 and pAkt in PBMCs (p < .05). There was no significant upregulation of pAkt(Ser(473)) in tumor tissue. Side effects were minimal and reversible. Conclusion. Significant inhibition of the mTOR pathway was noted in both tumors and PBMCs of HNSCC with minimal side effects. The mTOR inhibitors can potentially be used as adjuvant therapy for patients with minimal residual disease and PBMCs are potential surrogate markers in this setting. (C) 2010 Wiley Periodicals, Inc. Head Neck 32: 1619-1628, 2010
引用
收藏
页码：1619 / 1628
页数：10
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