A Phase II Study of the Role of Selective Cyclo oxygen ase-2 (COX-2) Inhibitor and Concurrent Chemoradiation as Adjuvant Postoperative Treatment in Patients with Locally Advanced Cancer Larynx

Objectives: The primary study objective is to determine the tolerability, acute toxicity profile and loco-regional recurrence (LRR) rate, 2 year relapse free survival (RFS) and overall survival (OS) with the use of selective COX-2 inhibitor, Celecoxib, concurrently with chemoradiotherapy (CRT) as adjuvant treatment for locally advanced squamous cell carcinoma (LASCC) of the larynx. Secondary end point is to study COX-2 expression and assess its prognostic significance with the pathological features and treatment outcomes. Patients and Methods: This study included 36 patients with histologically confirmed diagnosis of LASCC of the larynx after curative surgery stage III-IVA. All patients received Cisplatin 100mg/m² days 1,22 and 43 concurrently with external beam radiotherapy and celecoxib in a dose of 300mg twice daily during the whole course of radiotherapy. EBRT was delivered with conventional fractionation in a dose of 1.8-2 Gy/f to 50-54 + boost to high risk areas to 60-66 Gy in 30-33 fractions over 6-7 weeks using (6MV) with isocentric techniques. Tissue samples or paraffin blocks were obtained from eligible patients for detection of COX-2 expression by immunohistochemical method. Results: More than 75% of the patient had T2 tumors, 78% had positive lymph nodes and 80% had GI II tumors. Concurrent CRT and celecoxib were tolerable thus, 32 (89%) patients could proceed to receive a full course of Celecoxib, chemotherapy and radiotherapy. Overall, G3,4 acute toxicities were observed in 18/36 patients (50%) mainly chemotherapy related, but were well tolerated. Most G3 4 neuropenia which reported in 22% were transient and not complicated with toxic death on the protocol therapy. The worst nonhematalogic toxicities were mucositis (44%), GIT (36) and dysphagia (30%). With a median follow-up period of 27.6 months locoregional recurrence was observed in 17% of the patients. Kaplan-Meier method revealed two-year RFS of 67% and the two-year overall survival of 72%. COX- 2 was expressed in 61% of the patients and was significantly associated with grade I II, supraglottic site and positive lymph nodes. Correlation between COX-2 expression in the tumors and treatment outcomes revealed that overall recurrence was significantly increased in Cox-2 positive patients (73% Vs 27%) which was statistically significant (p 0.05). Additionally COX-2 positivity was associated with decreased 2 years RFS and 2-year overall survival but was not statistically significant (p 0.05).