ONCOmmunity

Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma

By: Ekshyyan O, Mills GM, Lian T, Amirghahari N, Rong X, Lowery−Nordberg M, Abreo F, Veillon DM, Caldito G, Speicher L, Glass J, Nathan CA.

Department of Otolaryngology − Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA.
Head Neck. 2010 Mar 10.

Abstract

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. © 2010 Wiley Periodicals, Inc. Head Neck, 2010.

PMID: 20222045 [PubMed − as supplied by publisher] Source: National Library of Medicine.

* Albert Einstein College of Medicine has been
awarded Acceditation with Commendation by
the ACCME