Oxaliplatin induces a rise of topoisomerases in PBMC of 53 cancer patients

leading to DNA adduct formation subsequently causing irreversible DNA replication error and apoptosis. Topoisomerase I and II (TPs) are critical enzymes for DNA function and cell survival. They control maintaining and modifying DNA topology during both replication and translation of genetic material, and restore DNA toxicity exerted by Platins. TPs-inhibitors drugs are largely used in chemotherapy, however, most often blindly of both the cancer tissue and the PBMC TPs status. Aim of the study: To evaluate the PBMC-TPs behaviour after OXP, and OXP followed by CPT11 administration. Patients and methods: Patients were 53 (23 F, 30 M; 37 to 80 years old, median age 65 years) with colon-rectal (29), lung (7), ovary and gastric (4 each), miscellaneous (9). TPI, IIa and IIb measurement was made by quantitative real-times RT-PCR. Test was made basally and after 1, 2, 3, 4, 5 hours after OXP (1 hr iv infusion) and also when OXP was followed by the administration of TPs inhibitor drug Irinotecan (CPT11; 1 hr-iv infusion). Results: After the OXP administration of a fast rise of TP I, IIa and IIb mRNA expression occurs (increment median percentage: 502%, 59,1% and 361%, respectively; p> 0.0001). 14 day after in the same patient, the CPT11 (sequentially given after OXP) markedly reduced the previously observed TPs rising (p> 0.0001). Conclusions: The timing of the TPs increase caused by OXP is rapid and it is cancelled by CPT11. Present results may help in constructing a combination chemotherapy regimen. The study is ongoing to enrol further patients. Present work is a part of the study program, and partly supports by AOI (Associazione Oncologica Italiana), and by Regione Veneto (N. 204/2004).