TS Gene Polymorphism Predicts Effect in Patients With Advanced Lung Cancer (TPEIAL)

A Multicenter, Open Clinical Trial of Using TS Gene Polymorphism to Predict Effect in Patients of Advanced Lung Adenocarcinoma to Pemetrexed Combining With Cisplatin Regiment as First-line Treatment

The investigators performed a multicenter, open trial of using TS gene polymorphism to predict advanced lung adenocarcinoma effect to pemetrexed combined with cisplatin regiment as first-line treatment.

Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer (NSCLC) primary treatment, normal organ function, and Eastern Cooperative Oncology Group performance status 0 to 2. All Patients were delivered to pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 for not less than 4 cycle, administered intravenously every 3 weeks. Response assessment was performed every 6 weeks; toxicity assessment was performed every 3 weeks. Primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), overall survival (OS), and toxicity. The study was designed to evaluate TS(thymidylate synthase) gene polymorphism as a predictor for advanced lung adenocarcinoma effect to pemetrexed combined with cisplatin regiment as first-line treatment. Polymorphisms of thymidylate synthase were investigated in peripheral WBC（white blood cell）of all patients.

TS high expression genotype delivered to pemetrexed 500 mg/m2 and cisplatin 75 mg/m2,for not less than 4 cycle, administered intravenously every 3 weeks.

TS low expression genotype delivered to pemetrexed 500 mg/m2 and cisplatin 75 mg/m2,for not less than 4 cycle, administered intravenously every 3 weeks.

'TS high expression genotype': pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of each 21 day,for not less than 4 cycle, administered intravenously every 3 weeks. 'TS low expression genotype': pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of each 21 day,for not less than 4 cycle, administered intravenously every 3 weeks.

Inclusion Criteria: histologic or cytologic proof of advanced lung adenocarcinoma primary treatment normal organ function Eastern Cooperative Oncology Group performance status 0 to 2 Exclusion Criteria: Symptomatic patients with brain metastases Major organ dysfunction and severe heart disease

Krawczyk P, Kucharczyk T, Kowalski DM, Powrozek T, Ramlau R, Kalinka-Warzocha E, Winiarczyk K, Knetki-Wroblewska M, Wojas-Krawczyk K, Kalakucka K, Dyszkiewicz W, Krzakowski M, Milanowski J. Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients. J Cancer Res Clin Oncol. 2014 Dec;140(12):2047-57. doi: 10.1007/s00432-014-1756-6. Epub 2014 Jul 16.

Wang X, Wang Y, Wang Y, Cheng J, Wang Y, Ha M. Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC. J Biomed Sci. 2013 Jan 25;20(1):5. doi: 10.1186/1423-0127-20-5.