Effect of COX-2 Selective or Non-Selective Inhibitors in Concurrent Chemoradiotherapy Againts Clinical Response and Immunohistochemistry Expressiion in Nasophartngeal Carcinoma
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Introduction. Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma derived from nasopharyngeal epithelial cells. It is estimated that there are approximately 10.000 new cases of NPC per year in Indonesia. NPC occupies the first rank of all head and neck cancers and the fifth rank of the whole body malignant tumors in Indonesia. The chief obstacle encountered in the treatment ofNPC is that most patients tend to come at advanced stages (stage III and IV), and even some come with unfavorable general condition. Radiotherapy is the treatment of choice for NPC management. Cellular expression of COX-2 increases above the normal level within the early stages of carcinogenes is, tumor progression, invasive tumor growth, carcinogenesis, inflammation, immune response suppression, apoptosis inh iilition, angiogenesis, tumor cell invasion and metastasis. Induction of COX-2 or its overexpression is associated with increased production of prostaglandins, including prostaglandin E2 (POE2). POE2 can influcncc p38 MAPK, EOFR, MMP-9, NF-id3, TNF-Cl and PPAR y. Several studies have shown the administration of COX-2 inhibitors towards cancer patients obtai ned positive results through chemopreventive and radiosensitization effect. The administration of COX-2 inhibitor is expected to increase the effect of standard therapy through chemopreventive and radiosensitization mechanism in order to decrease NPC progi·ess ion. Methods. A randomized double-blind clinical trial design. This study was conducted to reveal the effect of selective COX-2 inhibitor Etoricoxib and non-selective Piroxicam in concurrent chemoradiotherapy towards the clinical response and immunohistochemical expression in nasopharyngeal carcinoma. The subjects were divided into 3 treatment groups: 60 mg etoricoxib gro up, 20 mg piroxicam group and 60 mg Amylum-contained placebo group. Each group was orally administered once a day for 7 weeks. Results. A total of 25 subjects were examined in order to observe the effect of selective and nonselecti ve COX-2 inhibitor in concurrent chemoradiotherapy towards clinical response and immunohistochemical expression' in nasopharyngeal carcinoma. NPC patients most commonly occured in men (76 .0%), 4 1-60 year age group (56.0%) and histopathological type of squamous cell carcinoma (60.0%). Non-parametric test found a significant corre lation between the size of primary tumor, the size of lymph nodes and cli nical stage before and after chemoradiotherapy with COX-2 inhibitor group (p <0.05). As for the immunohistochemical findings revealed significant correlation between the expression of p38 MAPK and MMP-9 (p=0.046) from intervention group of etoricoxib before and after concurrent chemoradiotherapy. Conclusion. Significant correlation was found between the administration of selective COX-2 inhibitor Etoricoxib and the size of primalY tumor, lymph nodes and clinical stage, whereas nonselective COX-2 inhibitor Piroxicam and Amylum-contained placebo just showed significant correlation for the size of lymph nodes and cl inical stage (p <0.05) and significant correlation remained unfound for the size of prim ary tumor (p> 0.05). For the adm inistration of concurrent chemoradiotherapy with the addition of etoricoxib found significant decrease in both immunohistochemical expressions, p38MAPK and MMP-9 (p <0. 05).