THE ROLE OF THYMIDYLATE SYNTHETASE IN THE EFFICACY OF TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA WITH PEMETREXED/CISPLATIN REGIMENS VERSUS GEMCITABINE/CISPLATIN

DOI: https://doi.org/10.29296/25877313-2018-03-08
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Issue: 
3
Year: 
2018

T.D. Karpenko Thephysician of the Surgical Department №13 Thoraco-Abdominal Department, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow); Senior Laboratory Assistant, Department of Oncology, Faculty of Post-Graduate Further Education, MSMSU after. A.I. Evdokimov (Moscow) E-mail: katan4ik@list.ru N.A. Kozlov Ph.D. (Med.), Head of Pathology Department, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) E-mail: newbox13@mail.ru L.E. Rotobelskaya Research Scientist, Department of Radiology and Diagnosis, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) E-mail: lidar@mail.ru S.G. Bagrova Research Scientist, Department of Chemotherapy, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) B.E. Polotskiy Dr.Sc. (Med.), Professor, Senior Research Scientist, Thoracic Department of Thoraco-Abdominal Oncology Department, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) E-mail: polotskiy.boris@yandex.ru K.K. Laktionov Dr.Sc. (Med.), Head of the Department №13 Thoraco-Abdominal Department, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) E-mail: lkoskos@mail.ru M.B. Bychkov Dr.Sc. (Med.), Professor, Senior Research Scientist, Department of Chemotherapy, Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) E-mail: mbychkov77@yandex.ru

Standard 1-line treatment for disseminated MPM is systemic chemotherapy based on Platinum drugs in combination with pemetrexed or raltitrexed. This combination showed an increase of objective responses, time to progression, overall survival and quality of life compared with cisplatin alone. Another scheme of combination chemotherapy that was used with effective enough until the advent of pemetrexed in clinical practice is a combination of gemcitabine plus Platinum drugs. The objective effect can be obtained in 45% of patients dute to combined chemotherapy. We investigated whether thymidylate synthase (TS) expression is a predictive marker for the clinical outcome of pemetrexed/cisplatin in patients with malignant pleural mesothelioma. From January 2006 to November 2016 in the department of chemotherapy Federal State Budgetary Institution «SMRC Oncology. N.N. Blokhin» of the Russian Ministry of Health (Moscow) selected 53 patients who underwent the first line of treatment with pemetrexed or gemcitabine in combination with platinum. The average age was 52.5 years (from 29 to 76 years). There were 28 men (52.8%), women - 25 (47.2%). With stage II 3.4% (1), stage III - 30% (9) and with stage IV - 66.6% (20). Epithelioid MPM was detected - 73.3%. ECOG 0 - 36.7% (11), ECOG 1 53.3% (16) and ECOG 2 - 10% (3). All patients were divided into two groups depending on the expression of TS in tumor cells: TSnegative group 53.3% (16) and TS-positive group 46.6% (14). Additionally, patients were divided into two groups, depending on the chemotherapy regimen used. The rate of objective responses (ROO) in the TS-negative group was 55% in the pemetrexed / cisplatin group and 57% in the gemcitabine / cisplatin group. For TS-positive group accounted for 22% and 40%, respectively. The data allow us to consider the expression of TS as a potential prognostic marker. Additional prospective studies involving larger cohorts may confirm the predictive role of TS expression in tumor cells in the treatment of MPM.

Keywords: 
pleural mesothelioma
predictors of the effectiveness of chemotherapy
thymidylate synthetase

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