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, Jun Meng, Guichan Wang Department of Gynecology, Obstetrics, Yuhuangding Hospital, Yantai, Shandong Province, People’s Republic of China Aims: We aimed to comprehensively assess the risk of gastrointestinal toxicities associated with poly (ADP-ribose) polymerase inhibitors...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2018-09-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/risk-of-selected-gastrointestinal-toxicities-associated-with-poly-adp--peer-reviewed-article-DDDT |
| _version_ | 1818360966502416384 |
|---|---|
| author | Liu Y Meng J Wang G |
| author_facet | Liu Y Meng J Wang G |
| author_sort | Liu Y |
| collection | DOAJ |
| description | Yongping Liu, Jun Meng, Guichan Wang Department of Gynecology, Obstetrics, Yuhuangding Hospital, Yantai, Shandong Province, People’s Republic of China 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: poly (ADP-ribose) polymerase inhibitors, gastrointestinal toxicities, clinical trials, meta-analysis, targeted agents, gynaecological tumors, systematic review |
| first_indexed | 2024-12-13T21:09:11Z |
| format | Article |
| id | doaj.art-a005a54fe7c64d748dbc6b53d10cae95 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-13T21:09:11Z |
| publishDate | 2018-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-a005a54fe7c64d748dbc6b53d10cae952022-12-21T23:31:24ZengDove Medical PressDrug Design, Development and Therapy1177-88812018-09-01Volume 123013301940646Risk of selected gastrointestinal toxicities associated with poly (ADP-ribose) polymerase (PARP) inhibitors in the treatment of ovarian cancer: a meta-analysis of published trialsLiu YMeng JWang GYongping Liu, Jun Meng, Guichan Wang Department of Gynecology, Obstetrics, Yuhuangding Hospital, Yantai, Shandong Province, People’s Republic of China 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: poly (ADP-ribose) polymerase inhibitors, gastrointestinal toxicities, clinical trials, meta-analysis, targeted agents, gynaecological tumors, systematic reviewhttps://www.dovepress.com/risk-of-selected-gastrointestinal-toxicities-associated-with-poly-adp--peer-reviewed-article-DDDTPARA inhibitorsgastrointestinal toxicitiesclinical trialsmeta-analysis |
| spellingShingle | Liu Y Meng J Wang G 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 Drug Design, Development and Therapy PARA inhibitors gastrointestinal toxicities clinical trials meta-analysis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | PARA inhibitors gastrointestinal toxicities clinical trials meta-analysis |
| url | https://www.dovepress.com/risk-of-selected-gastrointestinal-toxicities-associated-with-poly-adp--peer-reviewed-article-DDDT |
| work_keys_str_mv | AT liuy riskofselectedgastrointestinaltoxicitiesassociatedwithpolyadpribosepolymeraseparpinhibitorsinthetreatmentofovariancancerametaanalysisofpublishedtrials AT mengj riskofselectedgastrointestinaltoxicitiesassociatedwithpolyadpribosepolymeraseparpinhibitorsinthetreatmentofovariancancerametaanalysisofpublishedtrials AT wangg riskofselectedgastrointestinaltoxicitiesassociatedwithpolyadpribosepolymeraseparpinhibitorsinthetreatmentofovariancancerametaanalysisofpublishedtrials |