A Phase II Study of the Role of Selective Cyclooxygenase-2
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- Category: Vol. 77, December 2009
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A Phase II Study of the Role of Selective Cyclooxygenase-2 (COX-2) Inhibitor and Concurrent Chemoradiation as Adjuvant Postoperative Treatment in Patients with Locally Advanced Cancer Larynx,NIVINE M.A. GADO, NASHWA NAZMY ABD ELAZIZ ABD ELKERIM, MANAL M. EL-MAHDY, KHALED NAGIB, WALEED BAYOMI, MOHAMAD SABRY and IMAN ELSHARAWY
Abstract
Objectives: The primary study objective is to determine the tolerability, acute toxicity profile and loco-regional recur-rence (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 carci-noma (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 nonhe-matalogic 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 asso-ciated 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).
Conclusion: Cox-2 may have prognostic value in predict-ing disease recurrence. Addition of Cox-2 inhibitors concur-rently with (CRT) was safe and tolerable, however its advantage over the standard CRT regimen couldn't be proved. Confir-matory randomized phase III trial on larger number of patients and longer follow-up is encouraged.