Effectiveness and safety of poly (ADP-ribose) polymerase inhibitors in cancer therapy: A systematic review and meta-analysis
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Zhengqiang Bao1,2,*, Chao Cao1,*, Xinwei Geng2, Baoping Tian1, Yanping Wu1, Chao Zhang1, Zhihua Chen1, Wen Li1, Huahao Shen1,3, Songmin Ying1,2
1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, China
2Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China
3State Key Laboratory for Respiratory Diseases, Guangzhou, China
*These authors have contributed equally to this work
Songmin Ying, e-mail: firstname.lastname@example.org
Huahao Shen, e-mail: email@example.com
Keywords: clinical trials, PARP, BRCA, cancer, synthetic lethality, Olaparib
Received: June 22, 2015 Accepted: August 28, 2015 Published: September 22, 2015
Poly (ADP-ribose) polymerase (PARP) inhibitors are a class of small-molecule drugs suppressing PARP enzymes activity, inducing the death of cells deficient in homologous recombination repair (HRR). HRR deficiency is common in tumor cells with BRCA gene mutation. Since their first clinical trial in 2003, PARP inhibitors have shown benefit in the treatment of HRR-deficient tumors. Recently, several randomized clinical trials (RCTs) have been conducted to investigate the potential benefit of administration of PARP inhibitors in cancer patients. However, the results remain controversial. To evaluate the efficiency and safety of PARP inhibitors in patients with cancer, we performed a comprehensive meta-analysis of RCTs. According to our study, PARP inhibitors could clearly improve progression-free survival (PFS), especially in patients with BRCA mutation. However, our study showed no significant difference in overall survival (OS) between the PARP inhibitors and controls, even in the BRCA mutation group. Little toxicity was reported in the rate of treatment correlated adverse events (AEs) in PARP inhibitor group compared with controls. In conclusion, PARP inhibitors do well in improving PFS with little toxicity, especially in patients with BRCA deficiency.
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