Repurposing drugs and immunogenic chemotherapy for cancer is an emerging field, especially the combination of drugs with validated data. Several studies have shown that enoxaparin, omeprazole, gemcitabine and bortezomib have immunomodulatory properties that synergize with several chemotherapeutic protocols and decrease chemoresistance in several tumors. We treated refractory patients with ECOG=0 with this combination. We demonstrated significant clinical response that correlated with the immune response after 2 months of weekly treatment.
CICS IRB approved this protocol and inform of consent was signed. We included 10 patients, median age 45 years old of each tumor with at least 2-4 relapses. The patients receive intravenous 0.5 gr/m2 of gemcitabine, 3.5 mg of bortezomib, 80 mg of omeprazole and enoxaparin was administrated subcutaneously in the area with more tumor activity according with the CT SCAN, Granzyme B ELISPOT and cytokine ELISA that were performed before, during and after the treatment. We analyzed the data with prism graph pad and by multivariate analysis using SAS/STAT.
We had a significant correlation between increased levels of CD8 cells (p = 0.0003) and PFS in the 100% of the patients. The cytokines measured were downregulated after the treatment with significant correlation with IL-6 (p = 0.001), IL-8 (p = 0.001), IL-18, (p = 0.01) and TNF alpha (p = 0.005) and CR after the third CT scans. The laboratory tests before, during and after the treatment did not demonstrate clinical significant toxicity.
The results obtained in this pilot study gave relevant data to prepare a phase I trial. We conclude that this combination is feasible to overcome chemoresistance and improve the anti-tumor immune response by CD8 cells and decreasing cytokines associated with tumor progression.
Clinical trial identification
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Legal entity responsible for the study
Centro de Investigacion de cancer en Sonora (CICS) campus Ciudad Obregon, Sonora, Mexico.
Fundacion del Centro de Investigacion de cancer en Sonora campus Ciudad Obregon
The author has declared no conflicts of interest.