Pharmacodynamic biomarkers in metronomic chemotherapy: multiplex cytokine measurements in gastrointestinal cancer patien
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ORIGINAL ARTICLE
Pharmacodynamic biomarkers in metronomic chemotherapy: multiplex cytokine measurements in gastrointestinal cancer patients Paloma Valenzuela1 · Derrick Oaxaca1 · Teresa Di Desidero2 · Karla Parra1 · Georgialina Rodriguez1 · Marian Manciu3 · Giacomo Allegrini4 · Alfredo Falcone5 · Guido Bocci2 · Robert A. Kirken1 · Giulio Francia1 Received: 12 May 2020 / Accepted: 16 September 2020 © Springer Nature Switzerland AG 2020
Abstract Metronomic chemotherapy has shown promising antitumor activity in a number of malignancies. We previously reported a phase II clinical trial of metronomic UFT (a 5-fluorouracil prodrug; 100 mg/twice per day p.o.) and cyclophosphamide (CTX; 500 mg/m2 i.v. bolus on day 1 and then 50 mg/day p.o.) plus celecoxib (200 mg/twice a day p.o.) in 38 patients with advanced refractory gastrointestinal tumors. The mechanisms of action of metronomic chemotherapy include inhibition of angiogenesis, direct cytotoxic effects on cancer cells, and, at least for drugs such as CTX, activation of the immune system. To further evaluate the latter, we carried out an immune system multiplex 14-cytokine profiling of plasma samples that were available (for day 0, day 28, and day 56) from 31 of the 38 patients in the above-noted clinical trial. Our results show that pre-treatment plasma-level cutoffs of interferon gamma (> 12.84 pg/ml), sCD40L ( 55.11 pg/ml), and IL-17a (
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