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

Abstract

AimsWe 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 methodsWe 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.ResultsA 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.ConclusionOur 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.

Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials

“…Because PARP inhibition is not selective to cancer cells, it eliminates the important mechanism of DNA repair of blood cells which are replaced more frequently like cancer cells, thus enhancing blood toxicity. In addition to increasing the risk of hematologic toxicities, another study showed that PARPis treatment significantly increased the risk of gastrointestinal toxicities at all levels in patients with ovarian cancer, except for constipation [46]. The frequent AEs recorded in these nine clinical trials that led to discontinuation of treatment and death in patients with PARPis were similar, which included anemia, thrombocytopenia, neutropenia, abdominal pain, intestinal obstruction, myelosuppression, nausea and vomiting.…”

Gastrointestinal events with PARP inhibitors in cancer patients: A meta‐analysis of phase II/III randomized controlled trials

“…A previous meta‐analysis 41 evaluated the risk of selected GI toxicities associated with PARP inhibitors in the treatment of ovarian cancer. They found that the risk of all‐grade GI toxicities associated with PARP inhibitors, excepting constipation, is significantly increased in ovarian cancer patients.…”

PARP inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective (Review)

“…It is considered best practice to follow-up new patients with lower blood counts at a weekly frequency, particularly in the case of bone marrow suppression due to previous chemotherapeutic regimens. ii) Gastrointestinal: Nausea, vomiting, diarrhea, constipation, difficulty in eating and anorexia (65), which tend to reduce in severity with time. iii) Other: Fatigue.…”