Abstract 3744: Acetylated tubulin (AT) levels predicts response to TPF chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC)

Abstract

Abstract Docetaxel acts by binding to β-tubulin, stabilizing microtubules, and causing cell cycle arrest in the G2/M phase of mitosis. Previous reports by our group suggest the absence of acetylated tubulin in tumor samples is a predictor for disease control in patients treated on a phase I trial with Docetaxel and Lonafarnib[1]. In this study, we hypothesize that patients with HNSCC with low levels of microtubule acetylation (i.e. highly dynamic microtubules) as measured by immunohistochemistry (IHC) would respond better to induction therapy with TPF (Docetaxel, Cisplatin and 5FU), and hence the level of acetylated tubulin (AT) would be a predictor of response to TPF. Method: Between July 5th 2006 and September 29th2009, 14 patients with HNSCC were enrolled in a Phase II clinical trial of induction chemotherapy with 3 cycles of TPF followed by local therapy. Patients underwent a biopsy of their primary tumor site prior to initiation of induction TPF. The IHC staining for AT expression was performed on formalin fixed paraffin embedded tissue. The scoring was based on intensity only since tumor cells displayed a homogeneous staining pattern. An AT score of 4 was considered to be high, whereas a stain of 0, 1, 2 or 3 was considered low. Primary tumor sites included oral cavity (OC; n=6), oropharynx (OP; n=5), larynx (L; n=1), sinus (S; n=1), and unknown primary (UP; n=1). All patients had stage IVa or IVb at presentation and had a performance status of 0-2 (Eastern Cooperative Oncology Group ECOG scale). All had at least one uni- or bi-dimensional measurable lesion on imaging. The study closed prematurely due to slow accrual and increased observed complications. A total of 9 patients were evaluated: OC/4, OP/5. Results: After 3 cycles of TPF induction chemotherapy, complete remission (CR) was achieved in 4/9(44.5%), partial remission (PR) in 4/9(44.5%), and progressive disease (PD) in 1/9(11%) of patients. There was a significant correlation between AT staining intensity and response to TPF (p=0.0476). Patients with complete response (CR) or good partial response (GPR) (>60% reduction in tumor measurement) had a significantly lower staining intensity. No correlation was observed between staining intensity and progression free survival (PFS) or overall survival (OS) perhaps due to the small sample size. Conclusion: AT expression seems to correlate with response to TPF chemotherapy in HNSCC. Predicting response to TPF may prove to be useful in customizing care for patients with HNSCC. We are planning a larger scale retrospective analysis of the value of AT expression in predicting outcome for patients with HNSCC. 1. Kauh J, et al., Defining the Interaction of Docetaxel and Lonafarnib in Patients with Advanced Malignancies. AACR meeting, 2008, LB-67, 2008. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3744.