Bazedoxifene as a novel strategy for treatment of pancreatic and gastric adenocarcinoma

Abstract

// Claudia Burkhardt 1 , Leo Bühler 1 , Matthieu Tihy 2 , Philippe Morel 1 and Michel Forni 3 1 Service de chirurgie viscérale, Département de chirurgie, Hôpitaux Universitaires de Genève, 1211 Genève, Switzerland 2 Département diagnostique Service de pathologie clinique, Hôpitaux Universitaires de Genève, 1211 Genève, Switzerland 3 Clinique de Carouge, Réseau la Tour, Avenue Cardinal Mermillod 1, 1227 Carouge, Switzerland Correspondence to: Leo Bühler, email: leo.buhler@hcuge.ch Keywords: cytokine receptor GP130; gastric adenocarcinoma; pancreatic adenocarcinoma; selective estrogene receptor modulator; STAT transcription factors Received: August 26, 2018     Accepted: February 19, 2019     Published: May 07, 2019 ABSTRACT Experimental studies have shown that the IL6/GP130/STAT3 pathway is involved in pancreatic cancer tumorigenesis and progression as well as in the development of other tumors. Bazedoxifene, a selective estrogene receptor modulator clinically available for the treatment of osteoporosis, has been shown to be an effective GP130/STAT3 signaling inhibitor through in vitro and small animal studies. Our aim was to investigate the effect of bazedoxifene on tumor progression in patients with advanced pancreatic and gastric tumors. We analyzed the data of 7 patients (5 suffering from pancreatic and 2 from gastric adenocarcinoma), with locally advanced and/or metastatic disease, median age 73 years old (range 48 – 86 years). Bazedoxifene was given orally at a dose of 20 mg per day for a median duration of 9 months (range 5 – 14 months). Two patients received bazedoxifene as monotherapy, 5 patients were under concomitant chemotherapy. Results showed tumor marker reduction in 5 patients, stable disease on CT in 5 patients and metabolic regression on PET-CT in 3 patients. Weight was gained in 4 patients. Two patients developed deep vein thrombosis and one pulmonary embolism, the treatment was otherwise well tolerated. An immunhistochemical study of pSTAT3 was performed in 6 patients, out of which 3 were positive. Our preliminary data indicate that bazedoxifene is a potential new therapeutic option for pancreatic and gastric cancer therapy, safe to use and at low cost. It might be administrated at an early stage with current strategies. Based on these preliminary results, we will initiate a prospective clinical study.