Network meta-analysis of triple therapy for the prevention and treatment of acute nausea and vomiting caused by emetogenic chemotherapy drugs with moderate and high risk / 中国药房

OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.

Network Meta-analysis of 5-HT3 Receptor Antagonists for Prevention of Acute Nausea and Vomiting Caused by High-dose Chemotherapy / 中国药学杂志

OBJECTIVE: To evaluate the efficacy of 5-HT3 antagonists in the prevention of acute nausea and vomiting caused by high-dose chemotherapy using the network Meta-analysis system. METHODS: Developing retrieval strategies, system retrieves electronic databases such as Pubmed, EMbase, Cochrane Library, VIP, Wanfang and CNKI (as of October 2018), to find a randomized controlled trial (RCT) that uses 5-HT3 receptor antagonist alone to prevent nausea and vomiting caused by high-dose chemotherapy in adults. Quality assessment and data extraction were performed on eligible RCTs, with outcomes including acute nausea and vomiting. The RESULTS of the included RCT studies were combined using traditional STA analysis and network Meta-analysis using STATA13.0 software and WINBUG software.The RESULTS of the included RCT studies were combined using traditional Meta-analysis and network Meta-analysis. RESULTS: A total of 20 studies were included, involving a total of 4 042 patients with high-dose emetogenic chemotherapy.Seven interventions were included (granstron, ondansetron, ramosetron, tropisetron, dolasetron, azasetron, and palonosetron) with a total arm count of 41.The traditional Meta RESULTS showed that palonosetron was more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy than ondansetron, and the difference was statistically significant (P0.05). Ondansetron may be inferior to granisetron (OR=1.238), but the difference is not statistically significant (P>0.05).For acute nausea caused by high-dose chemotherapy, ondansetron may be inferior to granisetron (OR=1.232), but the difference was not statistically significant (P>0.05).Ramosetron may be better than granisetron (OR=0.632), but the difference was not statistically significant (P>0.05).Network Meta-analysis found that ondansetron was inferior to palonosetron in the treatment of acute vomiting due to high-dose chemotherapy (OR=0.60, 95%CI:0.39-0.88). Palonosetron was superior to ramosetron (OR=2.54, 95% CI:1.16-5.80). SCURA RESULTS showed that the best treatment for acute nausea caused by high-dose chemotherapy was palonosetron, followed by ramosetron, dolasetron, ondansetron, granisetron and tropisetron. The best treatment for acute vomiting caused by high-dose chemotherapy is palonosetron, followed by ramosetron, azasetron, dolasetron, tropisetron, granisetron and ondansetron. The RESULTS of the network Meta-analysis are basically consistent with those obtained by traditional Meta-analysis. CONCLUSION: Compared with the first-generation 5-HT3 receptor antagonist, palonosetron is more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy, ramosetron is more effective than other first-generation 5-HT3 receptor antagonists. Whether the RESULTS of this study will guide the clinical practice still requires a large-scale prospective study designed specifically to verify.

Clinical analysis of aprepitant for treating vomiting caused by cis-platin regimen / 重庆医学

Objective To investigate the clinical efficacy of aprepitant in the treatment of cisplatin based chemotherapy in-duced nausea and vomiting.Methods The tumor patients treated with cisplatin(80 mg/m2)chemotherapeutic regimen in Affiliated Shantou Hospital of Sun Yat-Sen University from December 1,2014 to December 1,2016 were selected,61 cases still had vomiting after using granisetron and dexamethasone for routinely stopping vomiting,the patients with aprepitant and dexamethasone for fur-ther stopping vomiting served as the aprepitant group,while the patients with granisetron and dexamethasone as the granisetron group.Then the complete response(CR)rates within 24,24-72,>72-144 h were observed in the two groups.Results The CR rates within 24 h in the aprepitant group and granisetron group were 66.67% and 51.61% respectively,the difference was not sta-tistically significant(P=0.232),which at 24-72 h were 80.00% and 54.84% respectively,the aprepitant group was significantly better than the granisetron group(P=0.036),which at >72-144 h were 86.67% and 64.52% respectively,the aprepitant group was better than the granisetron group(P=0.045).The comparison of adverse reactions between the two antiemetic drugs found that constipation,diarrhea,urticaria,fatigue and anxiety had no significant difference(P>0.05),the occurrence rate of total adverse reactions in the aprepitant group was 23.33%,which in the granisetron group was 25.81%,the difference between the two groups was not statistically significant(P>0.05).Conclusion Aprepitant combined with dexamethasone has better effect for treating hy-peremetic chemotherapy drug cisplatin chemotherapy caused nausea and vomiting with good tolerance.

Efficacy and safety of multiple-dose 5-HT3 receptor antagonists in preventing multi-day-based and highly emetogenic chemotherapy-induced nausea and vomiting / 中国肿瘤临床

Objective:To evaluate efficacy and safety of multiple-dose tropisetron plus dexamethasone (DXM) versus palonosetron plus DXM for chemotherapy-induced nausea and vomiting. (CINV) in patients received multiple day-based highly emetogenic chemotherapy. Methods:Cancer patients who were receiving multiday-based highly emetogenic chemotherapy were randomly assigned to AB or BA groups. A randomized, cross self-control ed method was applied. Patients in AB group received palonosetron (0.25 mg) 30 min before chemotherapy on day 1 and 3 or additional day 5 in the first cycle;and with tropisetron (5 mg) 30 min before chemotherapy on day 1, 2, and 3, or sup-plementary days (day 4 and 5) in the second cycle. Patients in BA group were treated with tropisetron in the first cycle and with palonosetron in the second cycle. Tropisetron and palonosetron were administered with DXM (10 mg) on day 1, followed by additional doses (5 mg) on days 2 to 5. Palonosetron group comprised patients in the AB group in the first cycle and BA group in the second cycle, whereas tropisetron group included patients in the AB group in the second cycle and BA group in the first cycle. Efficacy and safety of tropisetron versus palonosetron in preventing CINV were evaluated. Results:Ninety-one patients were included in analyses. At day 3, 4, and 5, incidence rates of nausea in the palonosetron group reached 28.6%, 30.8%, and 24.2%, respectively, and those of the tropisetron group totaled 42.8%, 47.3%, and 39.6%, respectively (P<0.05). At day 4, 5, and 6, incidence rates of vomiting in the palonosetron group measured 28.6%, 18.7%, and 5.5%, respectively, and those of the tropisetron group reached 42.9%, 34.1%, and 14.3%, respectively (P<0.05). From day 4 to day 5, day 6 to day 7, and day 1 to day 7, the palonosetron group yielded significantly lower incidence rates of nausea and vomiting than tropisetron group (P<0.05). Rate of rescue treatment in the palonosetron group was lower than that in tropisetron group (13.2%vs. 24.2%, P=0.057). No statistical difference in toxicities was observed between the two groups. Conclusion:Palonosetron plus DXM features better efficacy than that of tropisetron plus DXM against delayed CINV induced by multiple day-based highly emetogenic chemotherapy, which was well tolerated in the two treatments.

Retrospective analysis of the clinical rational drug use refer to NCCN antiemetic guideline / 中国药学杂志

OBJECTIVE: To investigate the application of antiemetics in patients with gynecological cancers during chemotherapy. METHODS: Medical records of 182 patients receiving chemotherapy lor gynecological cancer were evaluated and a descriptive a-nalysis was carried out.Logistic regression was performed to determine the predictors of compliance. RESULTS: The rate of adherence to guideline (CINV) for patients receiving one-day chemotherapy is 80%. prophylactic usage rate in patients receiving multi-days chemotherapy is 95%, with a 47% 5-HT3 receptor antagonist.The adherence to NCCN anti-emesis guideline was better in patients having paclitaxel-based chemotherapy than patients having no paclitaxel. CONCLUSION: As the biggest cancer hospital in China, antiemetics were commonly given as prevention of CINV in the form of 5-HT3 receptor antagonist, but antiemetic effect of dexametha-sone was ignored and needed to be emphasized.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer / 부인종양

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

BACKGROUND/AIMS: A selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit. METHODS: Male guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm). RESULTS: The average charcoal transit was 51.3 +/- 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 +/- 21.9%, 46.9 +/- 9.14% and 8.4 +/- 5.6% of the total small intestine at the concentrations of 10, 30 and 100 microg/kg, respectively. GI transit after administration of TRH (100 microg/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 +/- 9.22%; TRH, 73.4 +/- 14.7%; MO, 81.0 +/- 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO. CONCLUSIONS: Ramosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.

Chemotherapy induced nausea & vomiting (CINV).

Chemotherapy is the first line treatment in management of many cancers, both for cure and palliation; hence it’s crucial to minimize the unpleasant side effects of chemotherapy to increase tolerability to chemotherapy. Most of the conventional anti cancer drugs are emetogenic. Patients receiving chemotherapy experience different degrees of nausea and vomiting depending on the emetogenic potential of the anti cancer drugs given and the patient characteristics. With a better understanding of the pathophysiology, distinct phases of chemotherapy-induced nausea and vomiting (CINV) i.e., acute emesis, delayed emesis and anticipatory emesis have been identified. Identification of various mediators has led to the development of different drugs acting through different mechanisms which are useful in the prevention and treatment of CINV. Serotonin receptor three (5-HT3) antagonists, corticosteroids and neurokinin type one receptor (NK-1) antagonists are of proven usefulness and have wide therapeutic indexes in the prevention of CINV. Other drugs like dopamine receptor antagonists & benzodiazepines are not routinely used because of their narrow therapeutic index. Practice guidelines for prevention of CINV will not only improve patient’s tolerability to chemotherapy & wellbeing, but also decrease hospital stay and overall cost of treatment of the patient.

Chemotherapy induced nausea & vomiting (CINV).

Chemotherapy is the first line treatment in management of many cancers, both for cure and palliation; hence it’s crucial to minimize the unpleasant side effects of chemotherapy to increase tolerability to chemotherapy. Most of the conventional anti cancer drugs are emetogenic. Patients receiving chemotherapy experience different degrees of nausea and vomiting depending on the emetogenic potential of the anti cancer drugs given and the patient characteristics. With a better understanding of the pathophysiology, distinct phases of chemotherapy-induced nausea and vomiting (CINV) i.e., acute emesis, delayed emesis and anticipatory emesis have been identified. Identification of various mediators has led to the development of different drugs acting through different mechanisms which are useful in the prevention and treatment of CINV. Serotonin receptor three (5-HT3) antagonists, corticosteroids and neurokinin type one receptor (NK-1) antagonists are of proven usefulness and have wide therapeutic indexes in the prevention of CINV. Other drugs like dopamine receptor antagonists & benzodiazepines are not routinely used because of their narrow therapeutic index. Practice guidelines for prevention of CINV will not only improve patient’s tolerability to chemotherapy & wellbeing, but also decrease hospital stay and overall cost of treatment of the patient.

Antidepressant and anxiolytic-like effects of 4n, a novel 5-HT3 receptor antagonist using behaviour based rodent models.

The present study was designed to investigate the putative antidepressant and anxiolytic-like effects of N-n-Butylquinoxalin-2-carboxamide (4n), a novel 5-HT3 receptor antagonist, with an optimal log P (2.01) and pA2 value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression and anxiety. Acute treatment of 4n (1-4 mg/kg, ip) in mice produced antidepressant-like effect in forced swim test (FST) without affecting the baseline locomotion in actophotometer test in mice. 4n (2-4 mg/kg, ip) treatment also potentiated the 5-hydroxytryptophan (5-HTP) induced head twitch response in mice. Further, 4n (1-4 mg/kg, ip) treatment antagonized reserpine induced hypothermia in rats. Chronic treatment (14 days) with 4n (1-4 mg/kg) and paroxetine (10 mg/kg) significantly attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in rats in modified open field paradigm. An anxiogenic-like behaviour was induced by light alone as the stimulus using light-dark aversion test. 4n (2-4 mg/kg, ip) treatment significantly increased no. of transitions between dark and lit area and the time spent in the lit area. In conclusion, these preliminary investigations confirm that 4n exhibited antidepressant and anxiolytic-like effects in rodent models of depression and anxiety.

5-HT3 receptors and irritable bowel syndrome / 国际儿科学杂志

Serotonin and its receptors exist extensively in gut,5-HT3 receptor is ligand-gated ion channel.It is composed of five subunits,S-HT3A ,5-HT3B ,5-HT3C ,5-HT3D and 5-HT3E .The genetics of serotonin receptors appear to be associated with irritable bowel syndrome.5-HTTLPR genetic polymorphisms influence the efficacy of serotonergic treatments. As a new generation of developed 5-HT3 receptor antagonists, alosetron and ramosetron act an important role in regulating gastrointestinal motility and visceral perception. They are efficacious in the treatment of irritable bowel syndrome. Ramosetron show high affinity for 5-HT3 receptors,dissociate slowly from 5-HT3 receptors and show long-lasting 5-HT3, receptor antagonism.

Cost-minimization Analysis of Treating Chemotherapy-induced Vomiting with 5 Kind of 5-HT_3 Receptor Antagonists / 中国药房

0.05);And the costs were 223.80,213.90,459.00,345.00 and 414.00 yuan,respectively.CONCLUSION: Granisetron Hydrochloride is the most economical one for vomiting induced by chemotherapy.

Open-label, Randomized Comparison of the Efficacy of Intravenous Dolasetron Mesylate and Ondansetron in the Prevention of Acute and Delayed Cisplatin-induced Emesis in Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed emesis. MATERIAL AND METHODS: From April 2002 through October 2002, a total of 112 patients receiving cisplatin- based combination chemotherapy were randomized to receive a single i.v. dose of dolasetron 100 mg or ondansetron 8 mg, 30 minutes before the initiation of chemotherapy. In the ondansetron group, two additional doses of ondansetron 8 mg were given at intervals of 2 to 4 hours. To prevent delayed emesis, dolasetron 200 mg p.o. daily or ondansetron 8 mg p.o. bid was administered from the 2nd days to a maximum of 5 days. The primary end point was the proportion of patients that experienced no emetic episodes and required no rescue medication (complete response, CR) during the 24 hours (acute period) and during Day 2 to Day 5 2 days (delayed period), after chemotherapy. The secondary end points included the incidence and severity of emesis. RESULTS: 105 patients were evaluable for efficacy. CR rates during the acute period were 36.0% for a single dose of dolasetron 100 mg, and 43.6% for three doses of ondansetron 8 mg. CR rates during the delayed period were 8.0% and 10.9%, respectively. There was no significant difference in the efficacy between the two groups. Adverse effects were mostly mild to moderate and not related to study medication. CONCLUSIONS: A single i.v. dose of dolasetron 100 mg is as effective as three i.v. doses of ondansetron 8 mg in preventing acute and delayed emesis after cisplatin- based chemotherapy, with a comparable safety profile.

Postoperative Suppression of Nausea and Vomiting by Preoperative Administ ration of 5-HT3 Receptor Antagonist Granisetronin Strabismus Surgery Under Topical Anesthesia

Traction of the extraocular muscles during strabismus surgery could cause nausea and vomiting in postoperative period. Although the extent of these symptoms would vary in wide range, sometimes they are so severe that patients may feel very uncomfortable and have difficulties with adjusting back to their routine life in immediate postoperative period. Authors have investigated whether the 5-hydroxytryptamin-3 [5HT3] receptor antagonist, which is now used as an effective antiememtic agent after general anesthesia and anticancer chemotherapy, can control the nausea and vomiting after strabismus surgery or not. As the occurrence of the oculocardiac reflex during strabismus surgery is closely related with postoperative emesis, we also examined if 5HT3 receptor antagonist can suppress the oculocardiac reflex as well. We performed strabismus surgery in 80 patients under topical anesthesia. In experimental group[N=40], 3 milligramof Granistron in 50 milliliter of normal saline was administered intravenously and in control group[N=40], the same amount of normal saline was administered one hour before the surgery. To evaluate the degree of nausea and vomiting, authors used the Rhodes 'Nausea and Vomiting Estimation Index[NVEI]and monitored heart rate for oculo-car-diac reflex. The NVEI in experimental group was 12.10 +/-5.60 compared with 16.85 +/-8.88 in control[P=0.005]. But there was no difference in frequency of oculocardiac reflex and the degree of heart rate decrement between the two groups [P=0.152, P=0.345]. In conclusion, Granisetron, 5HT3 receptor antagonist, is still effective in controlling the nausea and vomiting after strabismus surgery, but it has no suppressive effect on the oculocardiac reflex.

Postoperative Suppression of Nausea and Vomiting by Preoperative Administ ration of 5-HT3 Receptor Antagonist Granisetronin Strabismus Surgery Under Topical Anesthesia

Traction of the extraocular muscles during strabismus surgery could cause nausea and vomiting in postoperative period. Although the extent of these symptoms would vary in wide range, sometimes they are so severe that patients may feel very uncomfortable and have difficulties with adjusting back to their routine life in immediate postoperative period. Authors have investigated whether the 5-hydroxytryptamin-3 [5HT3] receptor antagonist, which is now used as an effective antiememtic agent after general anesthesia and anticancer chemotherapy, can control the nausea and vomiting after strabismus surgery or not. As the occurrence of the oculocardiac reflex during strabismus surgery is closely related with postoperative emesis, we also examined if 5HT3 receptor antagonist can suppress the oculocardiac reflex as well. We performed strabismus surgery in 80 patients under topical anesthesia. In experimental group[N=40], 3 milligramof Granistron in 50 milliliter of normal saline was administered intravenously and in control group[N=40], the same amount of normal saline was administered one hour before the surgery. To evaluate the degree of nausea and vomiting, authors used the Rhodes 'Nausea and Vomiting Estimation Index[NVEI]and monitored heart rate for oculo-car-diac reflex. The NVEI in experimental group was 12.10 +/-5.60 compared with 16.85 +/-8.88 in control[P=0.005]. But there was no difference in frequency of oculocardiac reflex and the degree of heart rate decrement between the two groups [P=0.152, P=0.345]. In conclusion, Granisetron, 5HT3 receptor antagonist, is still effective in controlling the nausea and vomiting after strabismus surgery, but it has no suppressive effect on the oculocardiac reflex.

Psychosis in Parkinson

Current treatment strategies for levodopa-induced psychosis in advanced Parkinson's disease have had limited success. Reduction or discontinuation of levodopa and coadministration with dopamine-blocking neuroleptics may attenuate the psychotic symptoms, but these strategies are associated with worsening of parkinsonian symptoms. Administration of 5-HT3 receptor antagonist ; ondansetron, a newer strategy to attenuate psychosis of Parkinson' disease without motor deterioration was introduced. A 41-year-old young-onset male, who was diagnosed as Parkinson's disease 7 years ago, was treated with levodopa therapy, and had levodopa-induced psychosis(delusion, hallucination, paranoid, insomnia). After trial of ondansetron, he showed improvement in the Brief Psychiatric Rating Scale(from 21 points to 9 points) in spite of increasing the dosage of levodopa. With ondansetron, we could increase the dosage of levodopa without psychotic complications(esp, hallucination), and he showed improvement in the motor fluctuation.