Natural Remedies for CINV (Chemotherapy-Induced Nausea and Vomiting)

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J Clin Hosp Pharm , Kris M, Gralla R, Clark R, et al: Incidence, course and severity of delayed nausea and vomiting following the administration of high-dose cisplatin. Cancer Invest , Grunberg S, Osoba D, Hesketh P, et al: Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity-an update.

Support Care Cancer , National Comprehensive Cancer Network: Antiemesis. Available at www. Accessed June 1, American Society of Health-System Pharmacists: ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm , Grunberg S: Advances in the management of nausea and vomiting induced by non-cisplatin containing chemotherapeutic regimens.

Blood Rev , Multinational Association for Supportive Care in Cancer. Perugia, Italy; March , Hesketh P, Navari R, Grote T, et al: Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer.

Navari R, Gandara D, Hesketh P, et al: Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. Gralla R, Navari R, Hesketh P, et al: Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy. Perez E, Hesketh P, Sandbach J, et al: Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: A multicenter, double-blind, randomized parallel study.

Chemotherapy induced nausea and vomiting

Oncologist , Kaiser R, Sezer O, Papies A, et al: Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P 2D6 genotypes. Cancer , Lancet Oncol , Gralla R, Lichinitser M, Van Der Vegt S, et al: Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol , Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: Results of a phase III, single-dose trial versus dolasetron.

Proc Am Soc Clin Oncol , Aapro M, Grunberg S, Manikhas G, et al: A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Hajdenberg J, Grote T, Yee L, et al: Infusion of palonosetron plus dexamethasone for the prevention of chemotherapy-induced nausea and vomiting.

J Support Oncol , Navari R: Role of neurokinin-1 receptor antagonists in chemotherapy-induced emesis: Summary of clinical trials.

CINV - Chemotherapy-induced Nausea and Vomiting

Ann Pharmacother , The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: A multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol Study Group. Warr D, Hesketh P, Gralla R, et al: Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy.

Support Cancer Care 14;, Navari R, Province P: Emerging drugs for chemotherapy-induced emesis. Expert Opin Emerg Drugs , Grote T, Hajdenberg J, Catmell A, et al: Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: Palonosetron, dexamethasone, and aprepitant.

Martin B, Wiley J: Mechanism of action of cannabinoids: How it may lead to treatment of cachexia, emesis and pain. Tramer M, Carroll D, Campbell F, et al: Cannabinoids for control of chemotherapy induced nausea and vomiting: Quantitative systematic review. BMJ , Bloechl-Daum B, Deuson R, Mavros P, et al: Delayed nausea and vomiting continue to reduce patients' quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. Herrstedt J: Risk-benefit of antiemetics in the prevention and treatment of chemotherapy-induced nausea and vomiting.

Expert Opin Drug Saf , Cohen L, de Moor CA, Eisenberg P, et al: Chemotherapy-induced nausea and vomiting: Incidence and impact on patient quality of life at community oncology settings. Support Cancer Care , Geling O, Eichler H: Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis?

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Systematic re-evaluation of clinical evidence and drug cost implications. The 5-HT3 receptor was identified as a potential mediator of the antiemetic effect, and various strategies were employed to develop selective 5-HT3 receptor antagonists, including: Screening indole analogues, leading to the development of ondansetron Structure-activity relationships around cocaine resulting in development of dolasetron Using serotonin as a basis, leading to the development of tropisetron Structure-activity relationships around tropisetron leading to granisetron.

Antiemetic efficacy superior to placebo and older antiemetics except high-dose metoclopramide No significant differences in antiemetic efficacy between the four drugs Antiemetic efficacy superior when combined with corticosteroids. Adverse effects largely confined to constipation and headache, although QTc prolongation has become a regulatory concern. While initial formulations were intravenous, the development of oral forms provided more convenient dosing.

Common Vitamins and Supplements to Treat chemotherapy-induced nausea and vomiting (cinv)

Moreover, there are several novel delivery methods for 5-HT3 receptor antagonists available, most notable of which are transdermal granisetron and sustained-release subcutaneous granisetron. The first-generation 5-HT3 receptor antagonists significantly improved emesis associated with cytotoxic chemotherapy, but nausea remains a persistent problem. Summary Palonosetron has several pharmacologic characteristics that set it apart from first generation serotonin 5-hydroxytryptamine-3; 5-HT3 receptor antagonists, including much higher affinity for the 5-HT3 receptor and a longer plasma half-life 40 hours versus 5—12 hours.

In terms of safety, while palonosetron has the same class-related adverse effects as first generation drugs, it is associated with significantly less mean QTc interval prolongation.

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Clinical trials demonstrated palonosetron to be associated with higher complete response rates for CINV in the delayed and overall, but not acute, phases, compared with first-generation 5-HT3 receptor antagonists. Palonosetron has demonstrated efficacy has part of triplet CINV prophylaxis regimens, in combination with aprepitant and dexamethasone, as well as in combination with olanzapine and dexamethasone. Cost-effectiveness studies have shown that while palonosetron was associated with higher acquisition and treatment costs than first-generation treatments, this was offset by reduced healthcare utilization for CINV, giving lower overall than those of other treatments.

All guidelines recommend palonosetron as the 5-HT3 receptor antagonist of choice in moderately emetogenic chemotherapy, with guidelines for highly emetogenic chemotherapy recommending a three-drug combination, comprising a 5-HT3 receptor antagonist, dexamethasone and an NK1 receptor antagonist or olanzapine. Summary Nausea and vomiting remain a clinically significant problem for patients receiving highly and moderately emetogenic chemotherapy.

The NK 1 receptor antagonists are aprepitant and fosaprepitant a prodrug of aprepitant , casopitant, netupitant and rolapitant. While the 5-HT 3 -mediated effect of emetogenic chemotherapy occurs within a few hours of administration, the NK 1 -mediated effect starts at approximately 15 hours after administration and continues past the acute phase into the delayed phase.

In clinical trials a fixed combination of netupitant and oral palonosetron NEPA has been shown to be associated with better control of nausea than palonosetron alone, even when used in subsequent cycles of chemotherapy. The addition of aprepitant to palonosetron and dexamethasone was found to be safe and effective in patients receiving high-dose chemotherapy and undergoing stem cell transplant. Summary International guidelines recommend that an NK1 receptor antagonist be given along with a 5-HT3 receptor antagonist and a steroid for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy, but not for those receiving moderately emetogenic treatment.

Researchers identified a total of published articles or abstracts related to the use of NK1 receptor antagonists in patients with cancer, with 13 journal articles and 3 abstracts a total of patients fitting the inclusion criteria. The beneficial effect of the addition of an NK1 receptor antagonist was most pronounced for patients receiving carboplatin-based chemotherapy and was comparable to that seen in patients receiving cisplatin-based highly emetogenic chemotherapy. Jordan K et al. Summary Assessment of nausea is challenging due to its subjective nature.

As a result many studies have evaluated nausea as either part of a complete response or as a secondary endpoint to emesis. Similar results were shown for the delayed phase in a study comparing aprepitant on days 2—3 with metoclopramide on days 2—4. Regarding the use of rolapitant, discrepancies between studies mean that no clear conclusions can be drawn regarding its use in nausea associated with highly emetogenic chemotherapy. NEPA is a fixed-combination antiemetic comprising netupitant and palonosetron, which has found to be associated with significantly better nausea control compared with oral palonosetron.

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Additional factors to consider when selecting an NK1 receptor antagonist for the control of chemotherapy-induced nausea include: Safety Schedule and convenience of administration, and implications of such for patient compliance The choice of 5-HT3 receptor antagonist International guideline recommendations.

Studies are needed to define the overall potential for chemotherapy-induced nausea in individual patients, including factors related to the patient and the disease, as well as to the specific anticancer treatments. Summary Early clinical trials revealed that, compared with dual therapy, triple therapy with aprepitant, a serotonin 5-hydroxytryptamine-3; 5-HT 3 receptor antagonist and dexamethasone provided improved control of acute and delayed CINV.

The safety and efficacy of aprepitant were subsequently evaluated in several milestone clinical trials in patients receiving highly emetogenic chemotherapy. Research into multiple-day dosing revealed: Aprepitant and fosaprepitant were more effective than ondansetron for control of delayed-phase emesis and need for rescue medication Aprepitant plus dexamethasone was effective for control of delayed emesis with highly emetogenic chemotherapy Aprepitant treatment was associated with significantly improved complete response rate over the total treatment period and during acute and delayed phases.

Chemotherapy-Induced Nausea and Vomiting: Which Antiemetic for Which Therapy?

Although originally recommended to be given for 3 days to control CINV, single doses oral or intravenous of aprepitant have been shown to be effective in preventing both acute and delayed CINV. Studies have also shown aprepitant to protect against CINV over multiple cycles of cisplatin-based chemotherapy, with control of CINV sustained over six cycles. Studies have shown aprepitant to be generally well tolerated. A systematic review of 17 trials of neurokinin-1 NK 1 receptor antagonists added to antiemetic regimens for the prevention of CINV showed statistically significant, but clinically trivial differences, in fatigue, hiccups and lower constipation than controls.

Importantly, aprepitant does not appear to alter the pharmacokinetics of high-dose melphalan when used as conditioning therapy prior to stem cell transplantation in patients with multiple myeloma. All clinical practice guidelines recommend aprepitant be added to combination 5-HT 3 receptor antagonist and dexamethasone for patients receiving highly emetogenic chemotherapy; adherence to antiemetic clinical practice guidelines resulted in a significantly reduced incidence of CINV. Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting CINV : A systematic review and meta-analysis This meta-analysis was conducted to investigate the efficacy of olanzapine compared with other antiemetics in both the prevention of chemotherapy-induced nausea and vomiting CINV and for breakthrough CINV.

Summary A total of 13 eligible randomised controlled trials were identified Ten in the preventative setting, with a total of patients randomised to olanzapine and to other serotonin 5-hydroxytryptamine-3; 5-HT 3 or neurokinin-1 NK1 receptor antagonists Three in the breakthrough setting, with a total of patients randomised to olanzapine and to other rescue antiemetics.

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The primary endpoints of the included studies were the percentage of patients achieving either no emesis or no nausea in the acute, delayed and overall phases. For the endpoint of no emesis in the acute phase, olanzapine was superior to other treatments, with a risk ratio RR of 1. Olanzapine was superior to other standard regimens for both no emesis and no nausea in the delayed phase, with RRs of 1.

In the overall phase, olanzapine was superior to other regimens for no emesis RR 1. For breakthrough treatment, the RRs also demonstrated statistical superiority of olanzapine over other rescue therapies for no emesis, which was the only endpoint available for meta-analysis, with a RR of 2.

Chemotherapy-induced Nausea and Vomiting

Subanalyses compared two doses of olanzapine: 5mg versus 10mg. Overall, results indicate that olanzapine is more efficacious than other standard antiemetics in the preventative and breakthrough CINV settings. Summary While effective treatments exist for the prevention of emesis in patients receiving chemotherapy, nausea is not as well controlled.

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Nausea can be difficult to measure, as it is a subjective sensation, the mechanisms of which have not been completely elucidated. The mechanisms by which olanzapine, an atypical antipsychotic drug, appears to work to reduce CINV are not completely understood, but the drug does block the neurotransmitters dopamine and serotonin, known mediators of CINV. Initially, a role of olanzapine as an antinausea treatment came from several case reports, which prompted a phase I study in which olanzapine was added to granisetron and dexamethasone in cancer patients receiving chemotherapy, followed by phase II studies using maximally tolerated doses from the phase I study.

Results of several phase III trials revealed that: Olanzapine was more frequently associated with a complete response CR of delayed CINV and improved quality of life in patients receiving moderately and highly emetogenic chemotherapy Olanzapine and aprepitant combined with palonosetron and dexamethasone were comparable in the control of chemotherapy-induced emesis, whereas nausea was better controlled with olanzapine Olanzapine was more effective for control of nausea than placebo in patients undergoing moderately or highly emetogenic chemotherapy and receiving a serotonin 5-hydroxytryptamine-3; 5-HT 3 receptor antagonist, dexamethasone and a neurokinin-1 NK 1 receptor antagonist.

Olanzapine has been shown to be effective in controlling both acute and delayed CINV in patients receiving single-day chemotherapy.