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O.V. Parshikov

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-053 - Thiol - Disulfide Ratio (TDR) in Blood as a Predictive in Vitro Test for Individualized Targeted Therapy Choice in Patients with Advanced NSCLC (ID 1380)

      09:30 - 17:00  |  Author(s): O.V. Parshikov

      • Abstract

      Despite the available positive results of targeted therapy (TT) in clinical oncology, more and more actual is a problem of preliminary screening of patients with solid tumors to whom TT will bring success. TDR is an integrated indicator of redox balance in biological cells which reflects dynamics of activity of a set of the thiol-containing cellular enzymes. It is known that the TDR level in a blood of cancer patients has a direct correlation with TDR in cancer cells. It assumes possibility of use change of TDR in a blood under the influence of drugs for indirect research of influence on biochemical processes in tumor cells. The possibility of prognosis of clinical efficacy and choice of effective targeting agents by means of TDR-test in blood in vitro in patients with advanced NSCLC was the purpose of the study.

      Between 09/11 and 10/14 we enrolled 52 treated patients (M/F - 44/8) with advanced NSCLC (stage IIIB/IV - 44/8); adenocarcinoma -21, squamous-cell carcinoma - 27, large-cell carcinoma - 4. The median number of prior chemotherapy regimens was 3 (range 1-6), median performance status - 1 (range 0 -3). Prior before TT course, patient’s blood was tested in vitro with targeting agents: erlotinib, gefitinib, cetuximab, trastuzumab, bevacizumab; the respons was evaluated on the dynamics of TDR during 24- our incubation. All the patients received two 4-week courses of treatment: the standard TT (control group, n=25) or such targeting agent susceptibility to which was confirmed by the TDR-test (study group, n=27). Clinical respons was evaluated by RECIST.

      After the end of treatment, the analysis of in vitro TDR reactions on the targeted agents tested showed direct correlation with the clinical results. According to the TDR-test, a portion of effective drugs was 50% - 100% in 92% of the patients, whose treatment resulted in regression or stabilization of disease. At the same time, in 94% of the patients, whose treatment resulted in progression of disease, a portion of effective agents was only 0 - 49%. Among the two groups of patients, objective clinical effects were observed in 7(26%) pts [(PR - 7(26%) pts, 95% CI: 11,6 - 55,2%), SD - 16(59%) pts, PD - 4(15%) pts)] in the study group versus 2(8)% pts [(PR - 2(8)% pts, 95% CI: 3,3 - 16,2%); SD - 8(32%) pts, PD - 15(60%) pts.)] in the control group; grade 3 and 4 toxicity was experienced by 1(4,0%) pt and 2(8%) pts, respectively, - in the control group, and by 1(3,7%) pt and 0, respectively, - in the study group. Sensitivity of the method used to choice efficacious targeting agent amounted to 91,8%, specificity (selectivity) was 94,5% in forecasting the cases resistant to targeting agent.

      The determination of individual sensitivity to targeted agents in patient’s blood in vitro by means of TDR- test is an effective method both for forecasting clinical efficacy of the treatment and for individual choice of TT in patients with advanced NSCLC. These findings need futher validation in additional clinical studies.