Local injection of anti-cancer drugs in an experimental model of colorectal cancer

Abstract

Purpose: Endoscopic resection of colorectal lesions significantly decreases the risk of colorectal cancer (CRC) incidence and death. Patients with invasive neoplasia or metastatic CRC have an evident poorer prognosis. Next step could be a more personalized treatment strategy, as a targeted therapy by direct injection of active substances in a selected lesion. The aim was to evaluate the efficacy of intratumoral injection of a drug-eluting platform (CoverGel) with different anti-cancer drugs in a rat model of azoxymethane (AOM)-induced CRC. Methods: Experimental CRC was induced in 20 rats. Animals were randomized in five groups (four each): CoverGel + Aflibercept (AFL), CoverGel + Bevacizumab (BVZ), CoverGel + Cetuximab (CTX), CoverGel + Panitumumab (PNT) and CoverGel + Irinotecan (IRT). Endoscopic, histological and necrosis score (0-3 scale) test were performed during follow-up to evaluate clinical success. Results: All animals developed invasive neoplasia (NICE 3, JNET 3), 7.2 mm as mean size (range 6 - 8). Intratumoral injection was feasible in all animals with no adverse events. AFL, an angiogenesis inhibitor agent, in comparison with the other medications (BVZ, CTX, PNT and IRT) obtained the best results: significantly reduction in tumor size (-30% vs. -10%, -3%, +2% and + 2%; p < 0.05, respectively) and significantly higher necrosis score (3 vs. 1, 0.3, 0 and 0; p < 0.05, respectively). Conclusion: Angiogenesis inhibitors medications produced the higher cell necrosis and reduction in tumor size in an experimental model of CRC. Intratumoral injection of a drug-eluting platform could open a new way to manage invasive CRC.