Treatment outcomes in poor metabolizers of cytochrome P450 2A6 with concurrent chemoradiotherapy in locally advanced head- and neck-squamous cell carcinoma.

Abstract

Human Cytochrome 2A6 (CYP2A6) is involved in the oxidative metabolism of the nicotine to the inactive cotinine. CYP2A6 is a primary enzyme in nicotine metabolism, the enzyme has been proposed as a novel target for smoking cessation. A total of 70 male patients of locally advanced head- and neck-squamous cell carcinoma confirmed by histopathological examination were enrolled in this study. All patients received concurrent chemoradiotherapy (total dose of 70 Gray in 35 fractions in 7 weeks with concurrent tablet capecitabine 1250 mg/m2/day). Response assessment was based on response evaluation criteria in solid tumor criteria. Total ribonucleic acid (RNA) was isolated from the whole blood of all patients by TRI REAGENT BD (SIGMA USA) followed by real-time polymerase chain reaction assay which was done in studying messenger RNA (mRNA) expression of Excision Repair Cross Complementation Group 1 in blood lymphocytes of patient. The most common stage prevalent was Stage IV A in 28 (56%) patients followed by Stage III in 16 (32%) patients. Out of 70, 20 (28.6%) patients defaulted for treatment, so the analysis was done in 56 patients. A total of 19 (34%) patients had a complete response (CR) and 17 (30%) patients had no response. In all the patients who had CR, posttreatment relative quantification (RQ) expression levels were high. Among nonresponders only three had higher RQ folds and the rest 14 had lower RQ folds. Posttreatment expression levels of CYP2A6 were found to be a better predictor for tumor response to the treatment than the pretreatment expression levels. Almost all the patients having higher RQ folds had CR and those having lower RQ folds had either no response or progressive disease on follow-up visits.