Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis

Abstract

BackgroundAlthough serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.MethodsWe searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.ResultsAfter screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13–4.17).For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.ConclusionsMost 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: (CRD42013003564).Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0761-9) contains supplementary material, which is available to authorized users.

CSTI-300 (SMP-100); a Novel 5-HT3Receptor Partial Agonist with Potential to Treat Patients with Irritable Bowel Syndrome or Carcinoid Syndrome

“…Upon reflection, it would appear that high levels of 5-HT 3 receptor inhibition are likely responsible for the severe constipation and possibly ischemic colitis. However, the latter side effect is likely a consequence of a multifactorial mechanism that includes the presence of IBS-d itself, since unmedicated patients can present this symptom and non-IBS-d patients receiving 5-HT 3 receptor antagonists for other indications (e.g., emesis), including at relatively high dosage, do not present ischemic colitis (Tricco et al, 2016).…”

Ramosetron as a Treatment for Cyclic Vomiting Syndrome: A Small-Scale Patient Trial

“…[2][3][4][5] Ondansetron, a serotonin 5-HT3 receptor antagonist, has been suggested as a therapeutic agent for CVS treatment, [6][7][8] but there has been no clinical trial of its efficacy. Ramosetron, another selective serotonin 5-HT3 receptor antagonist, [9][10][11] has been applied clinically for treatment of irritable bowel syndrome (IBS) in Japan. 12,13 Typical IBS symptoms (abdominal pain and/or diarrhea) are often observed in CVS cases.…”

Moxibustion for Chemotherapy‐Induced Nausea and Vomiting: A Systematic Review and Meta‐Analysis

“…Chemotherapy, a major cancer treatment, is aimed at ameliorating symptoms and prolonging patients' life [ 1 ]. However, nausea and vomiting are common side effects of chemotherapy in patients with cancer; these effects are defined as chemotherapy-induced nausea and vomiting (CINV) [ 2 , 3 ]. Neurotransmitters, such as 5-hydroxytryptamine, substance P, and dopamine, may play an important role in CINV.…”

“…CINV occurs in 70–80% patients treated with chemotherapy [ 2 , 3 ]. Although antiemetic drugs can ameliorate symptoms to a certain extent, they result in other side effects such as diarrhea, fatigue, headache, and transaminase elevation [ 6 ].…”

“…Furthermore, CINV negatively affects 20% patients' will to complete the cancer treatment [ 2 ]. Occasionally, patients postpone or refuse to continue chemotherapy because of the mentioned reasons [ 3 , 8 , 10 ]. Therefore, preventing and relieving CINV in patients with cancer have become a major concern in cancer treatment.…”