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Effect of coadministered beta blocker and COX-2 inhibitor to patients with pancreatic cancer prior to receiving albumin-bound (Nab) paclitaxel.
Background: Paclitaxel protein-bound particles nab-paclitaxel plus gemcitabine is rapidly becoming the standard of care for patients with metastatic adenocarcinoma of the pancreas (mPCa). Preclinical and clinical studies of beta-blockers and NSAIDs show a benefit of these drugs in pancreatic cancer. The aim of this study was to evaluate the impact of the co-administration of the beta blocker propranolol (P) and the selective COX-2 inhibitor etodolac (E) on survival of patients with mPCa receiving GemNab as standard of care. PE is presumed to target the adrenergic and prostaglandin stress systems activated in cancer that induce changes in tumor microenvironment, immune system, and HPA axis leading to tumor promotion and immune tolerance. Data on the use of nab-paclitaxel plus gemcitabine (GemNab) with a beta blocker and NSAID in the clinical setting is lacking. Methods: Patients with mPCa were eligible for this randomized investigator initiated trial. Patients received PE daily for one week prior to starting GemNab. PE was administered in a chronodosed regimen to maximize the therapeutic benefit and minimize side effects. The primary endpoint was survival. Twenty-three patients were randomized to either GemNab or GemNab after one week of propranolol and etodolac (PEGemNab). The median age was 62.8 years; 68.2% male. Pain at time of diagnosis as reported in 80% of the patients in the GemNab arm and in 76.9% of the PEGemNab arm and jaundice was observed in 40% and 23% of the GemNab and PEGemNab arms, respectively. Results: Progression free survival was 7.2 and 11.8 months in the GemNab and PEGemNab arms, respectively. Overall survival was 10.5 months for the GemNab arm and 15.9 months for the PEGemNab arm. The treatment was well-tolerated with no unexpected adverse events. Conclusions: Administration of PE one week prior to Paclitaxel protein-bound particles with gemcitabine significantly increased progression free and overall survival. No unexpected adverse reactions were seen. Additional data on cytokine and cancer markers will be presented.
Abstracts by Gouri Shankar Bhattacharyya:
Effect of coadministration of propranolol and etodolac (VT-122) plus sorafenib for patients with advanced hepatocellular carcinoma (HCC).Meeting: 2015 Gastrointestinal Cancers Symposium | Abstract No: 390
- Meeting: 2015 ASCO Annual Meeting | Abstract No: e13010