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.