Such interventions would have the potential to reduce the prevalence of chronic pain in the population .
Although certain risk factors can identify individuals who are most likely to develop chronic pain , few interventions to prevent chronic pain have been identified .
To facilitate the identification of preventive interventions , an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain .
We present general design considerations for prevention trials in population s that are at relatively high risk for developing chronic pain .
Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity
Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin ( FOLFOX ) regimen has become the st and ard adjuvant treatment for colorectal cancer . However , the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy . Many strategies have been proposed in order to manage the neurotoxicity , but their effect on antitumoral efficacy is still unclear . In this study , we investigated the effect of reduced glutathione administration on neurotoxicity , oxaliplatin pharmacokinetics , and platinum-DNA ( Pt-DNA ) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen . Twenty-seven patients were r and omized to receive GSH 1500 mg/m2 or saline solution before oxaliplatin infusion . Evaluation of neurotoxicity , pharmacokinetics of plasmatic total and ultrafiltered Pt , and determination of Pt-DNA adduct formation on white blood cells was performed during the 5th , 9th , and 12th cycles . At the end of all cycles of therapy , the patients in the GSH arm showed a statistically significant reduction of neurotoxicity ( P=0.0037 ) compared with the placebo arm . There were no significant differences in the main pharmacokinetic parameters between the two arms except a lower area under the plasma concentration – time curve and a smaller apparent steady-state volume of distribution ( Vss ) when GSH was coadministered . This difference can be explained by the natural function of GSH in the detoxification of oxaliplatin and by its ability to remove the Pt bound to plasma proteins . The determination of Pt-DNA adduct formation shows no statistically significant differences between the two arms . In conclusion , this study indicates that coadministration of GSH is an effective strategy to reduce the oxaliplatin-induced neurotoxicity without impairing neither the pharmacokinetics of oxaliplatin , nor the Pt-DNA adduct formation
Such interventions would have the potential to reduce the prevalence of chronic pain in the population .
Although certain risk factors can identify individuals who are most likely to develop chronic pain , few interventions to prevent chronic pain have been identified .
To facilitate the identification of preventive interventions , an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain .
We present general design considerations for prevention trials in population s that are at relatively high risk for developing chronic pain .