Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule.
OBJECTIVE
The aim of our study was to investigate if oxaliplatin (1-OHP) could be used as a radiosensitizer in vivo.


METHODS
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 (1 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.
Cividalli
Anna
A
Section of Toxicology and Biomedical Sciences, Agency for New Technology, Energy and Environment, Casaccia Research Center, Rome, Italy. cividalli@infos1.casaccia.enea.it
Ceciarelli
Francesca
F
Livdi
Esther
E
Altavista
Pierluigi
P
Cruciani
Giorgio
G
Marchetti
Paolo
P
Danesi
Donatella Tirindelli
DT
D000230:Adenocarcinoma / Q000532:radiotherapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy; D051379:Mice; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011838:Radiation-Sensitizing Agents; D000077150:Oxaliplatin; D002945:Cisplatin