Radiosensitization by oxaliplatin in a mouse adenocarcinoma: Influence of treatment schedule

Purpose: The aim of our study was to investigate if oxaliplatin (1-OHP) could be used as a radiosensitizer in vivo. Methods and Materials: Experiments were performed in mice (C3D2F1) bearing a transplanted mammary carcinoma in a foot. Drugs, 1-OHP and cis-diammine-dichloro-platinum (CDDP), were administered i.p. Results were analyzed in terms of tumor growth delay (TGD). Results: 1-OHP and CDDP were tested in single doses of 6 and 10 mg/kg body weight. Administration of either 1-OHP or CDDP produced a significant TGD but only with the dose of 10 mg/kg. Single dose combined X-ray (10 Gy) and 1-OHP (6 and 10 mg/kg) treatments were performed with different sequences and time intervals (I h, 4 h, and 24 h). All TGDs of these combined treatments were uniform among themselves (indicating that sequence and time interval did not influence the results), and did not depend on the drug dose. In X-ray (10 and 20 Gy) and 1-OHP (6 and 10 mg/kg) combined treatment, the TGDs increased only with X-ray dose. Different 1-OHP administration schedules were performed for fractionated experiments: two treatments every 4 days. The least toxic protocol (1-OHP total dose from 6 to 14 mg/kg) was selected for combined treatments with 10 daily X-ray treatments of 2 Gy. A clear drug dose-effect relationship was observed in those treatments with 1-OHP doses from 10 to 14 mg/kg. Conclusions: Although low-dose 1-OHP did not induce a TGD when administered alone, in combined protocols it increased X-ray efficacy. (C) 2002 Elsevier Science Inc.