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Meta-Analysis
. 2018 Sep 17:12:3013-3019.
doi: 10.2147/DDDT.S164553. eCollection 2018.

Risk of selected gastrointestinal toxicities associated with poly (ADP-ribose) polymerase (PARP) inhibitors in the treatment of ovarian cancer: a meta-analysis of published trials

Yongping Liu  1 , Jun Meng  1 , Guichan Wang  1
Affiliations
Meta-Analysis

Risk of selected gastrointestinal toxicities associated with poly (ADP-ribose) polymerase (PARP) inhibitors in the treatment of ovarian cancer: a meta-analysis of published trials

Yongping Liu et al. Drug Des Devel Ther. .

Abstract

Aims: We aimed to comprehensively assess the risk of gastrointestinal toxicities associated with poly (ADP-ribose) polymerase inhibitors (PARPis) in the treatment of ovarian cancer patients.

Materials and methods: We searched several databases for relevant trials. Eligible studies included prospective Phase II and III trials of ovarian cancer patients on the four PARPis (olaparib, veliparib, niraparib and rucaparib), describing events of nausea, vomiting, diarrhea, and constipation. Summary incidence, relative risk (RR), and 95% CIs were calculated employing fixed- or random-effects models.

Results: A total of 2,286 ovarian cancer patients from 12 trials were included for analysis. Our results showed that summary incidences of all-grade gastrointestinal events in ovarian cancer patients were nausea 68.8% (95% CI, 63.5%-73.6%), vomiting 36.2% (95% CI, 30.9%-41.8%), diarrhea 25.3% (95% CI, 21.2%-29.8%), and constipation 25.3% (95% CI, 17.9%-34.5%). The RRs of all-grade nausea, vomiting, diarrhea, and constipation were 2.00 (95% CI: 1.79-2.24; P<0.001), 2.12 (95% CI: 1.75-2.58; P<0.001), 1.20 (95% CI: 1.01-1.44; P=0.044), and 1.20 (95% CI: 0.88-1.80; P=0.21); respectively. While, the RRs of high-grade nausea, vomiting, diarrhea, and constipation were 3.74 (95% CI: 1.50-9.36; P=0.005), 2.81 (95% CI: 1.17-6.74; P=0.02), 0.56 (95% CI: 0.22-1.43; P=0.23), 0.92 (95% CI: 0.34-2.49, P=0.87); respectively.

Conclusion: Our study suggests that the risk of all-grade gastrointestinal toxicities associated with PARPis, excepting constipation, is significantly increased in ovarian cancer patients. And the use of PARPis significantly increased the risk of developing high-grade nausea and vomiting, but not for diarrhea and constipation. Close clinical monitoring is recommended when administering these drugs.

Keywords: clinical trials; gastrointestinal toxicities; gynaecological tumors; meta-analysis; poly (ADP-ribose) polymerase inhibitors; systematic review; targeted agents.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Studies eligible for inclusion in the meta-analysis.
Figure 2
Figure 2
Relative risk of all-grade GI toxicities in ovarian cancer treated with PARPis vs controls. Notes: (A) Nausea. (B) Vomiting. (C) Diarrhea. (D) Constipation. Abbreviations: Ev, events; Trt, treatment; Ctrl, controls; GI, gastrointestine.
Figure 3
Figure 3
Relative risk of high-grade GI toxicities in ovarian cancer treated with PARPis vs controls. Notes: (A) Nausea. (B) Vomiting. (C) Diarrhea. (D) Constipation. Abbreviations: Ev, events; Trt, treatment; Ctrl, controls; GI, gastrointestine.
See this image and copyright information in PMC

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90. - PubMed
    1. Siegel R, Ma J, Zou Z, Jemal A, Statistics C. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. - PubMed
    1. Bookman MA. Optimal primary therapy of ovarian cancer. Ann Oncol. 2016;27(Suppl. 1):i58–i62. - PubMed
    1. Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol. 2018;81(1):17–38. - PMC - PubMed
    1. Marth C, Reimer D, Zeimet AG. Front-line therapy of advanced epithelial ovarian cancer: standard treatment. Ann Oncol. 2017;28(Suppl. 8):viii36–viii39. - PubMed

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