EDTA enhances the antitumor efficacy of intratumoral cisplatin in s.c. grafted rat colon tumors

We have investigated whether EDTA, a calcium chelator, could improve the accumulation of platinum in tumors and enhance the antitumor efficacy by increasing drug diffusion through the extracellular tumor matrix. Intratumoral injection of 0.3 mg/kg cisplatin combined with 10 mg/ml EDTA in 2 ml saline serum led to tumor cure in four of eight rats and produced major tumor regression in the other animals. In contrast, intratumoral injection of cisplatin alone or EDTA alone had no antitumoral effect. EDTA increased platinum accumulation both in vivo and ex vivo in the PROb tumors. EDTA alone was cytotoxic at a concentration of 10 mg/ml, but neither increased platinum accumulation nor cisplatin toxicity on cultured PROb colonic cancer cells. We conclude that EDTA could be a useful and well-tolerated adjuvant for enhancing intratumoral cisplatin chemotherapy.