Prolonged administration of the granisetron transdermal delivery system reduces capecitabine plus oxaliplatin regimen induced nausea and vomiting.

OBJECTIVE: To evaluate the safety and efficacy of the granisetron transdermal delivery system (GTDS) combined with Dexamethasone for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving Capecitabine plus Oxaliplatin (CapeOX) therapy. DESIGN: Open-label, prospective, multi-center phase II trial. SETTING: Three institutions. PARTICIPANTS: Fifty-four patients scheduled to receive CapeOX chemotherapy. INTERVENTIONS: Participants received GTDS (3.1 mg applied to the upper arm 48 h before chemotherapy, replaced on day 5, and discarded on day 12) and Dexamethasone. MAIN OUTCOME MEASURES: The primary endpoint was the complete control rate of CINV. Secondary endpoints included the duration of delayed complete control, complete control rate in the acute phase, safety, and quality of life. RESULTS: The complete control rate for delayed CINV over the entire period (25-480 h) was 72.7% (95% CI 0.57-0.88). The duration of delayed complete control was 17.2 ± 4.5 days, with 51.5% of patients experiencing no nausea during the delayed phase. The complete control rate in the acute phase was 81.8% (95% CI 0.69-0.95). No serious adverse events related to the antiemetic regimen were reported. CONCLUSION: Prolonged administration of GTDS is safe and effective for preventing CINV in patients with gastrointestinal malignancies treated with CapeOX. TRIAL REGISTRATION: ClinicalTrials.gov registry (NCT05325190); registered on October 10, 2021.

The use of granisetron on bupivacaine induced sciatic nerve block in rats.

PURPOSE: The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonists on regional anaesthesia are complex and unclear. The present study was designed to test the hypothesis that granisetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor block, sensory block, and proprioception in a dose-dependent fashion in a rat model of bupivacaine-induced sciatic nerve blockade. MATERIALS AND METHODS: Thirty-eight male Wistar Albino rats that received unilateral sciatic nerve blocks were randomly divided into five experimental groups. Group B received a perineural of 0.3 ml of bupivacaine alone; Group BG800 received perineural 0.3 ml of bupivacaine and 800 µg of granisetron 10 min later; Group BG1200 received perineural 0.3 ml of bupivacaine and 1200 µg of granisetron 10 min later; Group BG1200IP received a perineural 0.3 ml of bupivacaine and an intraperitoneal injection of 1200 µg of granisetron 10 min later; and Group S was sham operated. A blinded investigator assessed motor, sensory and proprioception function every 10 min until the return of normal function. RESULTS: The medians for recovery times in Group B, Group BG800, Group BG1200, and Group BG1200IP were 105, 64, 85, and 120 min for motor function, respectively; 80, 64, 84, and 104 min for sensory function; 80, 63, 85, and 108 min were calculated for the proprioception function. The time to the return of normal motor, sensory, and proprioception function was not statistically significantly different between the groups (p > 0.05). Motor block did not develop in any of the rats in Group S. CONCLUSIONS: Local and systemic application of granisetron was not significantly decrease the duration of bupivacaine induced motor, sensory, and proprioception block of sciatic nerve in rat.

The Effect of Granisetron, Ondansetron, and Meperidine in Preventing Postoperative Shivering: Controlled Clinical Trial.

BACKGROUND: Recently, use of HT35 receptor antagonists to prevent postoperative shivering has attracted a great deal of attention. This study was conducted with the aim of investigating the effectiveness of granisetron as an HT35 antagonist when compared with ondansetron and meperidine in preventing postoperative shivering. MATERIAL AND METHODS: In this triple blind random clinical trial study, 90 patients 18-50 years of age with ASA Class I and II undergoing general anesthesia were randomly assigned into one of the three drug groups: O (4-mg ondansetron), G (40 µg/kg of granisetron), and P (25 mg meperidine), immediately before induction of anesthesia. After anesthesia induction, at the end of the surgery, after the entrance and after leaving the recovery state, central temperature, peripheral temperature, heart rate, systolic blood pressure, diastolic blood pressure, and shivering were measured and documented. Two-tailed P < 0.05 was considered significant. RESULTS: In the meperidine, ondansetron, and granisetron groups, 4 (13.3%), 3 (10%), and 10 (33.3%) of patients experienced shivering during recovery, where the difference between the ondansetron and granisetron groups was significant (p-value=0.02). The variations in the mean arterial pressure during the investigation stages only in the ondansetron group were not significant (p>0.05). At the beginning of recovery, the reduction of peripheral temperature significantly was lower in the ondansetron group (p<0.05), while reduction of the central temperature was significantly (p<0.05) higher in the granisetron group. By the end of the recovery, the variations in the peripheral temperature across the three groups were consistent with the changes at the beginning of recovery, but variations of the central temperature across the three groups was not significantly diverse. CONCLUSION: Granisetron was not found to be much effective in preventing postoperative shivering. Ondansetron and meperidine were equally effective in preventing postoperative shivering. Ondansetron also causes less hemodynamic changes compared to other drugs, while granisetron is more effective in terms of preventing nausea and vomiting.

Pharmacological augmentation of serotonin reuptake inhibitors in patients with obsessive-compulsive disorder: A network meta-analysis.

OBJECTIVES: The augmentation of serotonin reuptake inhibitors (SRIs) can be achieved by add-on therapy with different pharmacological agents in obsessive-compulsive disorder (OCD) for a better clinical outcome. This network meta-analysis (NMA) was conducted to evaluate and compare the effects of available augmentation agents for SRIs in OCD. METHOD: The data was extracted from 59 relevant clinical trials after a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and clinical trial registries. PRISMA guidelines were followed in data extraction, analysis and reporting. Random effects Bayesian NMA was done to pool the effects across the interventions for the change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scoring from baseline to the end of the study. Network graph was built, consistency model was run, node splitting analysis was performed, treatments were ranked as per SUCRA score and meta-regression was done for refractoriness to SRIs and duration of augmentation therapy as the predictor variables. RESULTS: The drugs showing significant reduction in YBOCS scoring were pregabalin (MD:-8.1;95% CrI: -16, -0.43), memantine (MD:-6.2;95% CrI: -9.9, -2.3), lamotrigine (MD:-6;95% CrI: -12, -0.47), ondansetron (MD:-5.7;95% CrI: -11, -0.67), granisetron (MD:-5.6;95% CrI: -11, -0.44), aripiprazole (MD:-5.4;95% CrI:-9.1, -1.6), risperidone (MD:-3.3;95% CrI: -6.4, -0.20) and topiramate (MD:-5.3;95% CrI: -9.6, -0.97). The node-split analysis showed that direct and indirect pooled effect sizes for all comparisons were comparable. Meta-regression showed a statistically non-significant association between YBOCS score reduction with the duration of augmentation therapy, but significant with SRI-refractory status. Finally, the results were sorted based on certainty of evidence. CONCLUSION: Memantine was found to be most effective augmentation agent for SRIs in OCD, followed by lamotrigine, ondansetron and granisetron with moderate certainty of evidence. The augmentation agents showed better symptom reduction in patients with SRI-refractory OCD in comparison to non-refractory OCD. PROSPERO REGISTRATION: CRD42022360110.

The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. METHODS: We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software. RESULTS: Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia. CONCLUSION: A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.

Effects of ondansetron, metoclopramide and granisetron on perioperative nausea and vomiting in patients undergone bariatric surgery: a randomized clinical trial.

INTRODUCTION: Post-operative nausea and vomiting (PONV) is a common problem after sleeve gastrectomy. In recent years, following the increase in the number of such operations, special attention has been paid to preventing PONV. Additionally, several prophylaxis methods have been developed, including enhanced recovery after surgery (ERAS) and preventive antiemetics. Nevertheless, PONV has not been completely eliminated, and the clinicians are trying to reduce the incidence of PONV yet. METHODS: After successful ERAS implementation, patients were divided into five groups, including control and experimental groups. Metoclopramide (MA), ondansetron (OA), granisetron (GA), and a combination of metoclopramide and ondansetron (MO) were used as antiemetics for each group. The frequency of PONV during the first and second days of admission was recorded using a subjective PONV scale. RESULTS: A total of 130 patients were enrolled in this study. The MO group showed a lower incidence of PONV (46.1%) compared to the control group (53.8%) and other groups. Furthermore, the MO group did not require rescue antiemetics, however, one-third of control cases used rescue antiemetics (0 vs. 34%). CONCLUSION: Using the combination of metoclopramide and ondansetron is recommended as the antiemetic regimen for the reduction of PONV after sleeve gastrectomy. This combination is more helpful when implemented alongside ERAS protocols.

Comparative Efficacy of Granisetron and Droperidol After Orthognathic Surgery for Prophylaxis of Postoperative Nausea and Vomiting: A Retrospective Study.

BACKGROUND: In the fall of 2021, granisetron was approved for postoperative nausea and vomiting (PONV) management in Japan. However, the comparative efficacy of droperidol and granisetron in the field of orthognathic surgery has not been determined. PURPOSE: We compare the efficacy of droperidol and granisetron for PONV prophylaxis following orthognathic surgery. STUDY DESIGN, SETTING, SAMPLE: We performed a retrospective cohort study of patients who underwent orthognathic surgery at a single institution from September 2020 to December 2022. Patients who had undergone Le Fort I osteotomy with sagittal split ramus osteotomy or isolated sagittal split ramus osteotomy were included. Patients were divided into three groups; the isolated droperidol (D), isolated granisetron (G), and droperidol with granisetron (DG) groups. General anesthesia was performed using total intravenous anesthesia for all patients; however, droperidol and granisetron were administered at the anesthesiologist's discretion. PREDICTOR VARIABLE: PONV prophylactic therapy included isolated droperidol, isolated granisetron, and droperidol with granisetron administration. OUTCOME VARIABLES: Postoperative nausea (PON) and postoperative vomiting (POV) were determined through medical examination within 48 hours following surgery. Secondary outcomes included complications due to droperidol and/or granisetron administration. COVARIATES: Age, sex, body mass index, Apfel's score, duration of surgery, duration of anesthesia, intraoperative blood loss, and type of surgery. ANALYSES: Statistical analysis was conducted using Fisher exact test, Mann-Whitney U test with Bonferroni correction for univariate comparison, and modified Poisson regression for comparison of PON and POV prophylactic efficacy for multivariate analyses. P values <.05 were considered statistically significant. RESULTS: Our study included 218 participants. There were no significant differences in covariates between groups D (n = 111), G (n = 52), and DG (n = 55). No significant difference in PON incidence was observed between groups. However, POV incidence was significantly lower in group DG than group D (relative risk, 0.21; 95% confidence interval, 0.05 to 0.86; P = .03). No significant difference in complication incidence was observed between groups. CONCLUSIONS AND RELEVANCE: Granisetron was as effective as droperidol for PONV management, while droperidol combined with granisetron was more effective than isolated droperidol for POV management. As compared to the use of each drug separately, their combination was considered safe, with no increase in complication rates.

Analgesic Effects and Adverse Reactions of Lidocaine for Patient-Controlled Intravenous Analgesia on Patients Undergoing Open Hepatectomy: A Retrospective Analysis.

PURPOSE: The aim of this study was to investigate the effect of lidocaine for patient controlled intravenous analgesia (PCIA) in patients who underwent open hepatectomy. DESIGN: A retrospective analysis. METHODS: A total of 281 patients who underwent open hepatectomy from July 2018 to December 2018 were included. All patients were assigned into two groups: the lidocaine group (PCIA consisted of lidocaine, sufentanil, tramadol and granisetron) and the control group (PCIA consisted of sufentanil, tramadol and granisetron). The postoperative visual analogue scale (VAS) and complications (including respiratory depression, hypotension, nausea and vomiting, pruritus, numbness of the corners of the mouth, dizziness) between the groups were compared. FINDINGS: There were no significant differences between the characteristics, duration of surgery and anesthesia, and recovery of postoperative activity between the two groups. In the first 3 days after the operation, the postoperative VAS score of the lidocaine group was lower than that of the control group at resting state, while after activity, the postoperative VAS contrast results were completely opposite. In particularly, the resting state at 48 hours (h) (1.05 ± 1.25 vs 1.57 ± 1.54) after surgery and the activity state at 72 h (3.02 ± 1.51 vs 2.2 ± 1.66) after surgery (P < 0.05). The incidence of mouth numbness and dizziness were significantly increased in the lidocaine group (P < 0.05). CONCLUSION: The addition of lidocaine in PCIA was not beneficial to improve the pain during activities and increased the incidence of perioral numbness and dizziness.

New Direct Limit on Neutrinoless Double Beta Decay Half-Life of

The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νßß) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νßß decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νßß decay half-life of T_{1/2}>3.6×10^{24} yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.

Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial.

BACKGROUND: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies. MATERIALS AND METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours). RESULTS: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. CONCLUSION: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267. IMPLICATIONS FOR PRACTICE: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.

Granisetron, a selective 5-HT3 antagonist, reduces L-3,4-dihydroxyphenylalanine-induced abnormal involuntary movements in the 6-hydroxydopamine-lesioned rat.

Administration of L-3,4-dihydroxyphenylalanine (L-DOPA) provides Parkinson's disease patients with effective symptomatic relief. However, long-term L-DOPA therapy is often marred by complications such as dyskinesia. We have previously demonstrated that serotonin type 3 (5-HT3) receptor blockade with the clinically available and highly selective antagonist ondansetron alleviates dyskinesia in the 6-hydroxydopamine (6-OHDA)-lesioned rat. Here, we sought to explore the antidyskinetic efficacy of granisetron, another clinically available 5-HT3 receptor antagonist. Rats were rendered hemi-parkinsonian by 6-OHDA injection in the medial forebrain bundle. Following induction of stable abnormal involuntary movements (AIMs), granisetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) or vehicle was acutely administered in combination with L-DOPA and the severity of AIMs, both duration and amplitude, was determined. We also assessed the effect of granisetron on L-DOPA antiparkinsonian action by performing the cylinder test. Adding granisetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) to L-DOPA resulted in a significant reduction of AIMs duration and amplitude, with certain parameters being reduced by as much as 38 and 45% (P < 0.05 and P < 0.001, respectively). The antidyskinetic effect of granisetron was not accompanied by a reduction of L-DOPA antiparkinsonian action. These results suggest that 5-HT3 blockade may reduce L-DOPA-induced dyskinesia without impairing the therapeutic efficacy of L-DOPA. However, a U-shaped dose-response curve obtained with certain parameters may limit the therapeutic potential of this strategy and require further investigation.

Granisetron attenuates liver injury and inflammation in a rat model of cecal ligation and puncture-induced sepsis.

BACKGROUND AND AIMS: Sepsis induced liver injury is recognized as a serious complication in intensive care units, it is deeply associated with oxidative stress, inflammation and subsequent pyroptosis. Hepatic pyroptosis known to aggravate sepsis-induced liver injury. Previous studies proved that granisetron has anti-inflammatory and antioxidant properties. Accordingly, this study aimed to evaluate the efficacy of granisetron on sepsis-induced liver damage using a cecal ligation and puncture (CLP) model in rats. MAIN METHODS: Male albino rats were randomly divided into four groups: a sham control group, a granisetron control group, a CLP-induced sepsis group and a granisetron-treated CLP group. Markers of oxidative stress, inflammation, pyroptosis-related proteins and liver function were measured in addition to the histopathological study. KEY FINDINGS: Granisetron pretreatment significantly decreased mortality and improved liver function, as indicated by decreased ALT, AST, and total bilirubin and increased albumin content. Moreover, granisetron increased GPx activity and downregulated hepatic MDA. Furthermore, granisetron administration significantly reduced TNF-α, IL-6, HMGB1 and NF-κB. It also decreased the expression of receptor for advanced glycation end and TLR4 in the liver tissue. Interestingly, granisetron inhibited pyroptosis as it reduced NLRP3, IL-1ß and caspase-1. Granisetron was shown to increase Nrf2 and HO-1. In addition, granisetron treatment repaired, to some extent, the abnormal architecture of hepatic tissue. SIGNIFICANCE: Our results suggested that granisetron is a potential therapeutic agent for sepsis-associated liver injury, possibly acting by inhibiting oxidative stress, inflammation and subsequent pyroptosis.

Effectiveness of palonosetron versus granisetron in preventing chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients' quality of life. Recently, studies have shown inconsistent antiemetic effects of two common 5-hydroxytryptamine 3 receptor antagonists, namely, palonosetron and granisetron. Therefore, we conducted a meta-analysis to evaluate the effectiveness of palonosetron versus granisetron in preventing CINV. METHODS: Relevant studies were obtained from PubMed, Embase, and Cochrane databases. The primary outcome was the complete response (CR) rate. Secondary outcomes were headache and constipation events. RESULTS: In total, 12 randomized controlled trials and five retrospective studies were reviewed. Palonosetron was consistently statistically superior to granisetron in all phases in terms of the CR rate (acute phases: odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.06-1.54; delayed phases: OR = 1.38, 95% CI = 1.13-1.69; and overall phases: OR = 1.37, 95% CI = 1.17-1.60). Moreover, a non-significant difference was found between the two groups in terms of the headache event, but the occurrence of the constipation event was lower in the granisetron group than in the palonosetron group. CONCLUSION: Palonosetron showed a higher protective efficacy in all phases of CINV prevention, especially in delayed phases, and no relatively severe adverse effects were observed.

A phase III study of transdermal granisetron versus oral ondansetron for women with gynecologic cancers receiving pelvic chemoradiation.

PURPOSE: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4-7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. METHODS: In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. RESULTS: Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2-64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4-56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. CONCLUSION: Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.

Effects of Palonosetron on Nausea and Vomiting Induced by Multiple-Day Chemotherapy: A Retrospective Study.

Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT3 RAs) and second-generation 5-HT3 RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT3 RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT3 RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.

Palonosetron versus Granisetron in Combination with Aprepitant and Dexamethasone for the Prevention of Chemotherapy-Induced Nausea and Vomiting after Moderately Emetogenic Chemotherapy: A Single-Institutional Retrospective Cohort Study.

The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1-3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0-24 h), delayed phase (24-120 h), and overall phase (0-120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

Potential drug-drug Interactions in hospitalized cancer patients: A report from the Middle-East.

INTRODUCTION: Patients suffering from solid tumors use a wide range of cytotoxic drugs. In this study, we aimed to detect, document, and descriptively analyze the potential drug-drug interactions in hospitalized solid tumor's patients in a Middle Eastern referral oncology-hematology University-affiliated hospital. MATERIALS AND METHODS: In this cross-sectional study, the medical record of solid tumor's patients who were admitted to the referral oncological center in Isfahan, Iran, during the six months period (2018) were considered. We included all patients who had received at least two chemotherapy or nonchemotherapy drugs simultaneously. The potential drug-drug interactions between chemotherapy and nonchemotherapy drugs were evaluated with Lexi-Interact ver.1.1 online software. RESULTS: During the study period, a total of 141 cancer patients were recruited, and their drug therapy regiment was thoroughly analyzed. We detected 227 drug-drug interactions with moderate or major severity out of included patients in which 96, 71, 32, and 28 interactions were in the category of C, D, B, and X, respectively. One hundred and fourteen patients (80.8%) encountered at least one potential drug-drug interactions during their hospitalization. Mechanistically, most of drug-drug interactions (56.4%) were pharmacodynamics. Interaction between granisetron and metoclopramide were the top 10 detected interaction (11.4%). The interaction between docetaxel and carboplatin was the most frequent drug-drug interactions between oncology drugs (2.6% of total drug-drug interactions). CONCLUSION: Potentially moderate or major drug-drug interactions frequently occur among solid tumor's cancer patients necessitate the establishment of a clinical pharmacy service for providing relevant pharmacotherapy consultations to prevent this potentially serious concern.

Gastric Serotonin Biosynthesis and Its Functional Role in L-Arginine-Induced Gastric Proton Secretion.

Among mammals, serotonin is predominantly found in the gastrointestinal tract, where it has been shown to participate in pathway-regulating satiation. For the stomach, vascular serotonin release induced by gastric distension is thought to chiefly contribute to satiation after food intake. However, little information is available on the capability of gastric cells to synthesize, release and respond to serotonin by functional changes of mechanisms regulating gastric acid secretion. We investigated whether human gastric cells are capable of serotonin synthesis and release. First, HGT-1 cells, derived from a human adenocarcinoma of the stomach, and human stomach specimens were immunostained positive for serotonin. In HGT-1 cells, incubation with the tryptophan hydroxylase inhibitor p-chlorophenylalanine reduced the mean serotonin-induced fluorescence signal intensity by 27%. Serotonin release of 147 ± 18%, compared to control HGT-1 cells (set to 100%) was demonstrated after treatment with 30 mM of the satiating amino acid L-Arg. Granisetron, a 5-HT3 receptor antagonist, reduced this L-Arg-induced serotonin release, as well as L-Arg-induced proton secretion. Similarly to the in vitro experiment, human antrum samples released serotonin upon incubation with 10 mM L-Arg. Overall, our data suggest that human parietal cells in culture, as well as from the gastric antrum, synthesize serotonin and release it after treatment with L-Arg via an HTR3-related mechanism. Moreover, we suggest not only gastric distension but also gastric acid secretion to result in peripheral serotonin release.

Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis-Induced Liver Injury by Granisetron Generation in Mice.

Sepsis-induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res; survived to 7 days after CLP) and sepsis-sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more-severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3 ) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokine expression by macrophages after lipopolysaccharide (LPS) challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed nuclear factor kappa B (NF-кB) transactivation and phosphorylated p38 (p-p38) accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels in septic patients. Conclusion: Our study indicated that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and associates granisetron as a hepatoprotective compound during sepsis development.