Abstract 341P
Background
Small cell lung cancer (SCLC) is highly aggressive and treated with etoposide plus a platinum-based agent, together with immunotherapy and concurrent chest radiotherapy. The current study examines in preclinical models the efficacy of TTFields together with the standard-of-care chemotherapies for the treatment of SCLC.
Methods
Human SCLC cells were treated with 150 kHz TTFields, DMS-53 cells with 1 V/cm RMS for 72 h, and H196 cells with 1.62 V/cm RMS for 120 h, alone or with cisplatin or etoposide at various concentration. Cell count, colony formation, and apoptosis were measured, and the overall effect calculated by multiplying cell count with colony formation. In vivo, C57BL/6 mice were orthotopically inoculated with murine KP3 SCLC cells and tumors were allowed to grow for 7 days. Then, TTFields or sham-heat were continuously applied for 9 days, and tumor volume examined at treatment end by magnetic resonance imaging (MRI).
Results
In both cell lines, TTFields application reduced cell count, induced apoptosis, and increased the overall effect relative to control. When TTFields were applied together with etoposide or cisplatin in H196 cells, a synergistic interaction was seen, which was higher with etoposide. In DMS-53 cells, TTFields concomitant with either of the chemotherapies showed an additive interaction in regards to cell count and a synergistic interaction per the overall effect, which matched the relatively high levels of apoptosis in this cell line. In mice, tumor growth was significantly reduced by TTFields treatment relative to control.
Conclusions
TTFields demonstrate efficacy for the treatment of SCLC in preclinical models, as stand-alone treatment and together with standard-of-care chemotherapies. Future in vitro and in vivo studies will test the efficacy of TTFields together with both chemotherapy agents, with immunotherapy, and with radiotherapy.
Legal entity responsible for the study
The authors.
Funding
Novocure.
Disclosure
U. Weinberg, R. Engelman, L. Somri-Gannam, T. Borkum, R. Blatt, D. Gerasimova, S. Cahal, C. Tempel Brami, M. Shai, E. Dor-On, I. Tzchori, A. Haber, M. Giladi: Financial Interests, Personal, Full or part-time Employment: Novocure; Financial Interests, Personal, Stocks/Shares: Novocure. Y. Palti: Financial Interests, Personal, Stocks/Shares: Novocure.