Poly (ADP-Ribose) Polymerase Inhibition for Chemotherapy-Induced Peripheral Neuropathy: A Meta-Analysis of Placebo-Controlled Trials.

Abstract

<b><i>Background:</i></b> Chemotherapy-induced peripheral neuropathy is characterized by pain, numbness, and tingling in the hands and feet and by diminished quality of life. Multiple previous studies, mostly preclinical, suggest that poly (ADP-ribose) polymerase (PARP) inhibitors may help with these symptoms. <b><i>Objective:</i></b> To assess the relationship between PARP inhibition and prevention/palliation of peripheral neuropathy in a clinical setting. <b><i>Design:</i></b> Meta-analysis of placebo-controlled clinical trials with PARP inhibitors. <b><i>Setting/Subjects:</i></b> We conducted 9 literature searches that included PubMed and other sources to compile fully published placebo-controlled clinical trials that tested PARP inhibitors and that reported on peripheral neuropathy. <b><i>Measurements:</i></b> The relative risks for neuropathy of all grades based on PARP inhibition were calculated for each trial. Each trial was weighted by its respective sample size. A forest plot was constructed. <b><i>Results:</i></b> Five trials, inclusive of 843 patients, met this study's eligibility criteria. Four included a concomitant PARP inhibitor (either olaparib or veliparib) and paclitaxel, a neuropathy-causing chemotherapy agent; the remaining trial evaluated long-term monotherapy with olaparib. The pooled overall relative risk for the development of neuropathy with PARP inhibition was 1.06 (95% confidence interval: 1-1.4). <b><i>Conclusions:</i></b> PARP inhibition does not appear to reduce the risk of chemotherapy-induced peripheral neuropathy. Whether PARP inhibitors may palliate (rather than prevent) neuropathy remains an area in need of further investigation.