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.
Duvillard
Christian
C
INSERM 517, Department of Pathology, Faculty of Medicine, Dijon, France. christian.duvillard@chu-dijon.fr
Ponelle
Tibor
T
Chapusot
Caroline
C
Piard
Françoise
F
Romanet
Philippe
P
Chauffert
Bruno
B
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004492:Edetic Acid / Q000008:administration & dosage*; D005260:Female; D015552:Injections, Intralesional; D009368:Neoplasm Transplantation; D051381:Rats; D012878:Skin Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D004492:Edetic Acid; D002945:Cisplatin