Palonosetron for Patients Undergoing High or Moderate Emetogenic Chemotherapy

This report identified high to moderate quality evidence from clinical studies and economic evaluations, as well as high-quality guidelines regarding the use of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adult and pediatric patients receiving different emetogenic chemotherapies. Interpretations of the findings should be taken with caution because of the presence of some identified limitations in both clinical and economic evidence. In adult patients receiving high emetogenic chemotherapy, a fixed antiemetic combination of netupitant and palonosetron (NEPA) plus dexamethasone demonstrated noninferiority relative to a triple regimen of granisetron-aprepitant-dexamethasone. Similarly, palonosetron had similar efficacy compared to granisetron with the co-administration of neurokinin 1 receptor antagonist (e.g., aprepitant or fosaprepitant) and dexamethasone. However, in the absence of aprepitant, a 2-drug combination of palonosetron-dexamethasone appeared to be significantly more effective than granisetron-dexamethasone for the prevention of both acute and delayed emesis. In adult patients receiving moderate emetogenic chemotherapy, palonosetron plus dexamethasone was found to be noninferior compared with ondansetron plus dexamethasone. Similar efficacy was also observed between palonosetron plus dexamethasone and transdermal granisetron plus dexamethasone. In a mixed population of adult patients receiving high or moderate emetogenic chemotherapy, a palonosetron regimen appeared to have greater efficacy than ondansetron for delayed emesis. The efficacy of triple regimen of palonosetron-aprepitant-dexamethasone and granisetron-aprepitant-dexamethasone was comparable at all phases. In pediatric patients receiving high emetogenic chemotherapy, palonosetron plus dexamethasone had similar efficacy compared with ondansetron plus dexamethasone in the acute phase, but was more effective in delayed and overall phases of chemotherapy-induced nausea and vomiting. In a mixed population of pediatric patients receiving high or moderate emetogenic chemotherapy, palonosetron plus dexamethasone was noninferior to ondansetron plus dexamethasone. There were no significant differences between palonosetron and ondansetron or between palonosetron and granisetron treatment regimens in adverse events or quality of life. A cost-utility analysis revealed that NEPA plus dexamethasone was dominant (i.e., cost less, more effective) relative to granisetron-aprepitant-dexamethasone and ondansetron-aprepitant or fosaprepitant-dexamethasone in adult patients receiving high emetogenic chemotherapy. In contrast, double or triple regimens of palonosetron was not cost-effective compared to granisetron regimens, mainly due to large difference in price and small quality-adjusted life-years gained. These economic evaluations may not be applicable to the Canadian context. The identified high-quality guidelines have recommendations on the use of specific antiemetic regimens for adult and pediatric patients receiving high emetogenic chemotherapy or moderate emetogenic chemotherapy and suggest that palonosetron may be offered as an alternative to other 5-hydroxytryptamine-3 receptor antagonists and that 1 5-hydroxytryptamine-3 receptor antagonist is not preferred over another based on the available evidence.

A Photo Stability Indicating HPLC technique for Validation of Netupitant and Palonosetron in Bulk and Formulations

Analytical chemistry is the science that seeks ever improved means of measuring the chemical composition of natural and artificial materials.Netupitant Delayed emesis has been largely associated with the activation of tachykinin family neurokinin 1 receptors. Palonosetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally and peripherally in turn inhibits the visceral afferent stimulation of the vomiting center.The mobile phase used was orthophosphoric and acetate 70% buffer pH 3 and 30% methanol.The assay of Netupitant and Palanosetron was performed with tablets and the % assay was found to be 100.08 and 100.04, The linearity was found to be linear with a correlation coefficient of 0.999, the precision 0.8 and 0.3 for Netupitant and Palanosetron which shows that the method is precise.The validation of developed method shows that the accuracy is well within the limit, which shows that the method is capable of showing good accuracy and reproducibility. The LOD and LOQ for Netupitant were found to be 3.02 and 9.98 and LOD and LOQ for Palanosetron was found to be 3.00 and 10.00. Thus, it shows that the method is stability indicating, sensitive, accurate, robust and precise. Hence, the developed HPLC method can be successfully applied to the pharmaceutical dosage form and can be used for routine analysis.

Effects of Xiao-Ban-Xia-Tang Formula on Cisplatin and 1-phenylbiguanide Hydrochloride Induced Emesis and Gut Microbiota in the Pica Model of Rats

Background: In this study, the effects of Xiao-Ban-Xia-Tang (XBXT) formula on cisplatin and 1-phenylbiguanide hydrochloride (1-PBG) induced acute and delayed emesis and gut microbiota were studied in the pica model of rats, compared with ondansetron. Methods: Two rat models of cisplatin and 1-PBG induced pica were established, the amount of kaolin intake was observed, and the effects of XBXT and ondansetron on the gut microbiota were further studied by 16S rDNA gene analysis. Results: The results showed that the total intake of kaolin of the rats injected with cisplatin and 1-PBG was significantly increased, and treatment of XBXT and ondansetron could significantly ameliorate the acute and delayed pica induced by cisplatin and 1-PBG. The 16S rDNA gene analysis has shown that the alpha diversity of the gut microbiota of the cisplatin and 1-PBG treated rats was significantly decreased compared with the control group, and ondansetron could further decrease the alpha diversity of the gut microbiota of the rats treated with cisplatin. Ondansetron significantly decreased the relative abundance of Firmicutes and increased the abundance of Bacteroidetes on phylum level in the cisplatin and 1-PBG treated rats, while XBXT only decreased Firmicutes in the cisplatin treated rats. Conclusions: XBXT was as effective as ondansetron in the treatment of acute and delayed pica induced by cisplatin and 1-PBG in rats. Ondansetron was more likely to cause gut microbiota dysbiosis than XBXT. Our study provided new avenues for the roles and mechanisms of XBXT on the prevention and treatment of CINV.

Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract

Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study

Purpose: To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel. Methods: This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2–5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index–Emesis (FLIE) questionnaire, and patient’s satisfaction with antiemetic coverage. Results: Fifty-two percent of patients in arm A ( P=0.406), 59% in arm B ( P=0.779), and 67% in arm C had a delayed TC. Secondary analyses showed no significant difference across arms in any efficacy endpoint. FLIE scores as well as mean satisfaction scores were similar across arms. Conclusions: In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

A retrospective study of a dexamethasone-sparing strategy of preventing acute and delayed emesis caused by CapeOx regimen with aprepitant for colorectal cancer.

632 Background: CapeOx therapy which is combination with oxaliplatin (L-OHP) and capecitabine is one of the standard treatments for first line chemotherapy for unresectable colorectal cancer, or for postoperative adjuvant chemotherapy for stage III colon cancer. L-OHP-based regimen is classified as moderately emetogenic chemotherapy. In the SENRI trial which we previously conducted as phase III trial, aprepitant, an NK-1 antagonist, showed the efficacy for prevention of emesis against L-OHP. On the other hand, even when in highly emetogenic chemotherapy, it is reported that dexamethasone after day 2 could be spared. Methods: We retrospectively reviewed chemo-naive 94 patients with colorectal cancer who underwent CapeOx therapy at our institution from April 2012 to March 2017. We assessed the relationship between emesis during the first cycle of CapeOx (day1-5) and the use of dexamethasone on day 2-3. Results: 10 patients underwent CapeOx plus bevacizumab, and 84 underwent CapeOx. All patients received 5-HT3 receptor antagonist (palonosetron: 87, granisetron: 7). 50 patients received aprepitant on days 1-3 and dexamethasone on day 1 (APR+D1 group). 22 patients received aprepitant on days 1-3 and dexamethasone on days 1-3 (APR+D3 group). 15 were dexamethasone on days 1-3 without aprepitant (D3 group), and 7 were dexamethasone only on day 1 without aprepitant (D1 group). Acute complete response (CR; no vomiting and no rescue anti-emetics) rates were 100% in any groups. Delayed CR rate was 56% in APR+D1 group, 86% in APR+D3 group, 53% in D3 group, and 29% in D1 group, respectively. In multivariate linear regression with aprepitant, there was a significant difference in presence of dexamethasone (p = 0.028). Conclusions: Acute emesis could be prevented by even only 1-day administration of dexamethasone when combined with the triplet prophylactics. However, in order to sufficiently prevent delayed emesis induced by L-OHP, it was suggested that addition of DEX on days 2 and 3 might be better.

A retrospective review of treatment patterns of antiemetic agents for chemotherapy-induced nausea and vomiting

Objectives: To evaluate the treatment pattern of antiemetic agents used for chemotherapy-induced nausea and vomiting in a tertiary hospital in Saudi Arabia. Methods: Over a period of 7 weeks, all new chemotherapy order sheets were collected and evaluated for chemotherapy-induced nausea and vomiting management. We compared each antiemetic regimen used for chemotherapy-induced nausea and vomiting prophylaxis with three international antiemetic guidelines by the following organizations: the Multinational Association of Supportive Care in Cancer, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network for the clinician. Results: A total of 152 cancer patients were included in the study, for whom 289 chemotherapy physician orders included antiemetic regimens. Approximately 17.3% of the chemotherapy protocols had total minimal emetogenicity risk, 22.5% had low risk, 37.02% had moderate risk, and 23.18% had high risk. For acute emesis, 27.57% of the antiemetic regimens followed at least one of the three reference guidelines. For delayed emesis, only 20.16% of the antiemetic regimens adhered to at least one of the three reference guidelines. Conclusion: Adherence to treatment recommendations and antiemetics prescribing for chemotherapy-induced nausea and vomiting was suboptimal at this hospital. However, institutional antiemetic guidelines and oncology pharmacists could play an important role in better assessment and management of chemotherapy-induced nausea and vomiting.