Prevention and treatment of anticipatory chemotherapy-induced nausea and vomiting in pediatric cancer patients and hematopoietic stem cell recipients: Clinical practice guideline update.

This 2021 clinical practice guideline update provides recommendations for preventing anticipatory chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. Recommendations are based on systematic reviews that identified (1) if a history of acute or delayed CINV is a risk factor for anticipatory CINV, and (2) interventions for anticipatory CINV prevention and treatment. A strong recommendation to optimize acute and delayed CINV control in order to prevent anticipatory CINV is made. Conditional recommendations are made for hypnosis, systematic desensitization, relaxation techniques, and lorazepam for the secondary prevention of anticipatory CINV. No recommendation for the treatment of anticipatory CINV can be made.

A randomized trial of nurse-administered behavioral interventions to manage anticipatory nausea and vomiting in chemotherapy.

PURPOSE: Chemotherapy side effects diminish quality of life and can lead to treatment delay. Nausea and vomiting can occur prior to chemotherapy because of classical conditioning. We studied the effects of 20-minute behavioral interventions, administered by oncology nurses, of higher intensity (mindfulness relaxation-MR) or lower intensity (relaxing music-RM), on anticipatory nausea and vomiting (ANV). PATIENTS AND METHODS: Patients undergoing chemotherapy for solid tumors were randomized to MR (N = 160), RM (N = 159), or standard care SC (N = 155). Subjects were mostly female (91.8%) and white (86.1%) with breast cancer (85%). Most patients had early stage disease (Stage I: 26%; II: 52.9%; III: 19%; IV: 0.1%). Anticipatory nausea and vomiting were assessed at the midpoint and end of the chemotherapy course using the Morrow Assessment of Nausea and Emesis (MANE). RESULTS: Compared to SC, there was reduced anticipatory nausea at the midpoint of chemotherapy in those receiving MR (OR 0.44, 95% CI 0.20-0.93) and RM (OR 0.40, 95% CI 0.20-0.93), controlling for age, sex, cancer stage, and emetogenic level of chemotherapy. There was no difference between treatment groups in anticipatory nausea at the end of chemotherapy or in anticipatory vomiting and postchemotherapy nausea and vomiting at either time point. CONCLUSION: A brief nurse-delivered behavioral intervention can reduce midpoint ANV associated with chemotherapy.

Suppression of acute and anticipatory nausea by peripherally restricted fatty acid amide hydrolase inhibitor in animal models: role of PPARα and CB1 receptors.

BACKGROUND AND PURPOSE: Effective treatments of nausea are limited. In this study we evaluated the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937, to suppress acute and anticipatory nausea in rats and examined the pharmacological mechanism of this effect. EXPERIMENTAL APPROACH: We investigated the potential of URB937 (administered i.p.) to reduce the establishment of lithium chloride-induced conditioned gaping (model of acute nausea) and to reduce the expression of contextually-elicited conditioned gaping (model of anticipatory nausea) in rats. The role of CB1 receptors, CB2 receptors and PPARα in the anti-nausea effect of URB937 was examined. The potential of URB937 to suppress FAAH activity in tissue collected from the area postrema (AP), prefrontal cortex (PFC), liver and duodenum and to elevate levels of FAAH substrates - anandamide (AEA), N-oleoylethanolamide (OEO) and N-palmitoylethanolamide (PEA) - in the AP was also evaluated. KEY RESULTS: URB937 reduced acute nausea by a PPARα-dependent mechanism and reduced anticipatory nausea by a CB1 receptor-dependent mechanism. The PPARα agonist, GW7647, similarly attenuated acute nausea. URB937 reduced FAAH activity in the liver and the duodenum but not in the PFC. In addition, URB937 reduced FAAH activity and elevated levels of fatty-acid ethanolamides in the AP, a brain region that is not protected by the blood-brain barrier. CONCLUSIONS AND IMPLICATIONS: The anti-nausea action of URB937 may occur in the AP and may involve PPARα to suppress acute nausea and CB1 receptors to suppress anticipatory nausea.

Incidence and predictors of anticipatory nausea and vomiting in Asia Pacific clinical practice--a longitudinal analysis.

PURPOSE: Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy-induced NV (CINV) on the incidence of anticipatory NV in later cycles. METHODS: This multicenter, prospective non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3. RESULTS: Five hundred ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%). The incidence of clinically significant anticipatory nausea (score of ≥3) was 4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p < 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea. CONCLUSIONS: These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles.

Overshadowing as prevention of anticipatory nausea and vomiting in pediatric cancer patients: study protocol for a randomized controlled trial.

BACKGROUND: Emesis and nausea are side effects induced by chemotherapy. These effects lead to enormous stress and strain on cancer patients. Further consequences may include restrictions in quality of life, cachexia or therapy avoidance. Evidence suggests that cancer patients develop the side effects of nausea and vomiting in anticipation of chemotherapy. Contextual cues such as smell, sounds or even the sight of the clinic may evoke anticipatory nausea and vomiting prior to infusion. Anticipatory nausea and vomiting are problems that cannot be solved by administration of antiemetica alone.The purpose of the proposed randomized placebo-controlled trial is to use an overshadowing technique to prevent anticipatory nausea and vomiting and to decrease the intensity and duration of post-treatment nausea and vomiting. Furthermore, the effect on anxiety, adherence and quality of life will be evaluated. METHODS/DESIGN: Fifty-two pediatric cancer patients will be evenly assigned to two groups: an experimental group and a control group. The participants, hospital staff and data analysts will be kept blinded towards group allocation. The experimental group will receive during three chemotherapy cycles a salient piece of candy prior to every infusion, whereas the control group will receive flavorless placebo tablets. DISCUSSION: If an effectiveness of the overshadowing technique is proven, implementation of this treatment into the hospitals' daily routine will follow. The use of this efficient and economic procedure should aid a reduced need for antiemetics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30242271/

Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients.

PURPOSE: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. METHODS: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1" = "Not at all Nauseated" and "7" = "Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. RESULTS: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001). CONCLUSIONS: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.

Preoperative hypnotherapy in the management of a child with anticipatory nausea and vomiting.

A six-year-old boy with oesophageal strictures secondary to neonatal repair of oesophageal atresia and requiring six to eight weekly oesophageal dilatations by bouginage developed anticipatory nausea and vomiting. This was effectively managed by a course of preoperative hypnotherapy over four sessions. Resolution of anticipatory nausea and vomiting occurred along with cessation of postoperative nausea and vomiting. This case supports early intervention with preoperative hypnotherapy in children with anticipatory nausea and vomiting that has not responded to other measures.

The continuing problem of post chemotherapy nausea and vomiting: contributions of classical conditioning.

Despite continuing improvements in antiemetic therapies, nausea and vomiting following chemotherapy treatments for cancer remain significant clinical problems for many patients. The role of classical conditioning in patients' anticipatory nausea is well known, but little attention has been paid to possible conditioning effects on post treatment nausea. The present study statistically examined the contribution of anticipatory (conditioned) nausea to patients' subsequent post treatment nausea. Forty early stage breast cancer patients who developed anticipatory nausea were analyzed. Results revealed a significant correlation between the intensity of anticipatory nausea in the clinic prior to their treatment infusion and subsequent post treatment nausea during the 24 h after the infusion. These results provide support for the hypothesis that, once established, conditioned nausea may contribute to the severity of subsequent post treatment nausea in patients receiving repeated cycles of chemotherapy for cancer. The results suggest the importance of considering the contribution of conditioning process to nausea and other post treatment side effects.

[Relationship between neurotransmitter blood noradrenalin and nausea/emesis after chemotherapy for lung cancer].

A clinical study was conducted to investigate the relationship between nausea/emesis after chemotherapy for lung cancer (docetaxel 60 mg/m(2), cisplatin 80 mg/m(2)) and blood serotonin (S), blood catecholamine (adrenaline) (A), noradrenaline (NA) and dopamine (D) in effective and non-effective patients treated with anti-emetic agents. All 37 patients received preventive combination administration of granisetron (GR) 3 mg, methylprednisolone 500 mg and metoclopramide (ME) 40 mg immediately before chemotherapy, followed by GR 3 mg and ME 40 mg on Day 2 and 3. Sixteen patients who were classified as emotionally unstable according to the YG character test additionally received prochlorperazine 15 mg thrice daily starting after their last meal prior to chemotherapy, until nausea/emesis disappeared. Blood concentration was measured on the day before chemotherapy and on Day 2, 4, and 14 after administration of the anticancer agents. As a result, a significant difference was demonstrated for NA on the day before chemotherapy (p<0.05), NA on Day 14 (p<0.01) and D on Day 14 (p<0.01) between effective and non-effective patients receiving anti-emetic treatment. In addition to conventional neurotransmitters S and D, NA is also worthy of attention in connection with nausea/emesis.

[Comparison of ramosetron and azasetron for prevention of acute and delayed cisplatin-induced emesis in lung cancer patients].

We performed a retrospective study that compared the efficacy and safety of ramosetron with azasetron in a case of acute and delayed emesis induced by cisplatin (CDDP)-included chemotherapy in patients with lung cancer. The study subjects were 100 lung cancer patients treated with combination therapy of cisplatin, ifosfamide, irinotecan (CIC therapy). The ramosetron group and azasetron group received, respectively, ramosetron 0.3 mg or azasetron 10 mg intravenous injection, 30 minutes prior to CDDP. All patients received 32 mg of dexamethasone intravenously. Protection from emesis showed no significant difference between two treatment groups. However, the grade of nausea was significantly lower in the ramosetron group than in the azasetron group. Furthermore, chlorpromazine hydrochloride for use as a rescue medication was required by significantly fewer in the ramosetron group than in the azasetron group. Adverse effects were observed in 27 cases in the ramosetron group and 24 cases in the azasetron group. However, because the symptoms were all mild, we did not consider there was any safety problem. In conclusion, it was suggested that ramosetron is a clinically useful treatment for acute and delayed emesis induced by cisplatin-induced chemotherapy in patients with lung cancer.

[Evidence-based management of nausea and vomiting].

One of the most common chemotherapy-related adverse reactions has been nausea and vomiting. With the recent advances in supportive care, however, it has become possible to prevent most of the chemotherapy-induced nausea and vomiting. This article summarizes the ASCO guideline published in 1999 and the 2004 NCCN guideline together with the recent advances in this field.

[Olanzapine use in cancer patients for refractory vomiting].

Recent investigations suggest the efficacy of olanzapine in cancer patients with intractable vomiting or chemotherapy-induced nausea. Olanzapine,indicated for schizophrenia in Japan, has an affinity for multiple neurotransmitter receptors including dopaminergic, serotonergic, histaminergic, adrenergic and muscarinic receptors. This pharmacological activity thus has a potential role in the treatment of nausea and vomiting. In the present study, olanzapine was given to five cancer patients with refractory vomiting to standard medications. In 3 cases, olanzapine resolved vomiting completely and also improved anorexia, In 2 cases, vomiting was controlled for a limited period. No adverse effect was observed. These results suggest olanzapine is a useful agent for the management of both vomiting and anorexia.

[Principles of managing chemotherapy-induced nausea and vomiting].

Chemotherapy-induced nausea and vomiting (emesis) can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. For patients treated with emetogenic chemotherapy, it is very important to prevent nausea and vomiting completely. The incidence and severity of nausea and/or vomiting in patients receiving chemotherapy are affected by numerous factors, including: 1) the specific chemotherapeutic agents used; 2) their dosage; 3) the schedule and route of administration; and 4) individual patient variability. Approximately 70 to 80% of all cancer patients receiving chemotherapy experience emesis, whereas 10% to 44% experience anticipatory emesis. The following general principles are recommended. 1) A 5-HT3 receptor antagonist should be administered prior to each day's 1st dose of moderately or highly emetogenic chemotherapy. 2) Dexamethasone should be administered once daily either orally or intravenously for every day of moderately or highly-emetogenic chemotherapy and for 2-3 days after chemotherapy for regimens that are likely to cause significant delayed-emesis. 3) The most effective way to treat anticipatory nausea and/or vomiting is to prevent it by using optimal antiemetic therapy during every cycle of treatment.

Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: An animal model of anticipatory nausea and vomiting.

Chemotherapy patients report not only acute nausea and vomiting during the treatment itself, but also report anticipatory nausea and vomiting upon re-exposure to the cues associated with the treatment. We present a model of anticipatory nausea based on the emetic reactions of the Suncus murinus (musk shrew). Following three pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit conditioned retching in the absence of the toxin. The expression of this conditioned retching reaction was completely suppressed by pretreatment with each of the principal cannabinoids found in marijuana, Delta(9)-tetrahydrocannabinol or cannabidiol, at a dose that did not suppress general activity. On the other hand, pretreatment with a dose of ondansetron (a 5-HT(3) antagonist) that interferes with acute vomiting in this species, did not suppress the expression of conditioned retching during re-exposure to the lithium-paired context. These results support anecdotal claims that marijuana, but not ondansetron, may suppress the expression of anticipatory nausea.

[A randomized crossover study of ramosetron plus dexamethasone for the prevention of nausea and vomiting induced by chemotherapy including cisplatin-comparison of ramosetron combined with 8 mg and 12 mg of dexamethasone].

A randomized crossover study between 0.3 mg of ramosetron (RAM) combined with 8 mg of dexamethasone (DEX) and 0.3 mg of RAM combined with 12 mg of DEX was performed to investigate the prevention of nausea and vomiting due to chemotherapy including 60 mg/m2 or 70 mg/m2 of cisplatin (CDDP) in patients with advanced head and neck squamous cell carcinoma (HNSCC). Twenty-five patients the study consisted of who received chemotherapy with CDDP were enrolled in the present study between January 2001 and December 2002 at the Yokohama City University School of Medicine or Yokohama City University Medical Center. The antiemetic effectiveness in the group receiving 12 mg of DEX was not significantly superior to the group receiving 8 mg of DEX. It was suggested that the antiemetic therapy of RAM 0.3 mg plus DEX 8 mg was effective for the prevention of nausea and vomiting induced by CDDP in patients with advanced HNSCC.

Comparison of ramosetron and granisetron for the prevention of acute and delayed emesis in Cisplatin-based chemotherapy: a randomized controlled trial.

OBJECTIVE: A clinical study of ramosetron was carried out to evaluate its efficacy in preventing both acute and delayed emesis in cisplatin-based chemotherapy by using a double-blind method with granisetron as the comparative drug. METHODS: Cisplatin at a dose of > or =70 mg/m(2) was administered as a single intravenous (i.v.) infusion over 4 h. Patients were randomly assigned to receive either ramosetron (0.3 mg i.v. bolus 30 min before cisplatin on Day 1 and a 0.1 mg tablet in the morning for Days 2 to 5 after completion of chemotherapy; n = 36) or granisetron (3 mg i.v. infusion 30 min before cisplatin on Day 1 and a 1 mg tablet in the morning for Days 2 to 5 after completion of chemotherapy; n = 37). The observation period started with the initiation of chemotherapy (0 h) and continued for 24 h after completion of the chemotherapy for acute emesis, and on Days 2 to 5 for delayed nausea and vomiting. RESULTS: A total of 73 patients were eligible for evaluation, with 36 patients in the ramosetron group and 37 in the granisetron group. The efficacy of both drugs was analyzed in terms of the degree of achievement in each day of treatment. Ramosetron was as effective as granisetron in preventing nausea and vomiting (both acute and delayed emesis). The two drugs had a similar safety profile and adverse events were generally mild and transient. CONCLUSIONS: Ramosetron is effective and safe for the control of acute and delayed emesis induced by cisplatin.

[Preventive efficacies of china-made tropisetron hydrochloride and Navoban on chemotherapy-induced nausea and vomiting: a randomized controlled clinical trial].

BACKGROUND & OBJECTIVE: Navoban (import tropisetron hydrochloride) can effectively prevent chemotherapy-induced nausea and vomiting; however, it is too expensive to be used extensively in clinic. This study was designed to compare the antiemetic efficacies and side effects of China-made tropisetron hydrochloride with Navoban. METHODS: A multicenter and randomized controlled trial was carried out. A total of 132 cancer patients were randomized into 2 groups and received 5 mg of China-made tropisetron hydrochloride (group A, 66 patients) or Navoban (group B, 66 patients) intravenously before cisplatin- or adriamycin-based chemotherapy. The gastrointestinal reactions induced by chemotherapy and side effects of the antiemetics were recorded within 7 days after chemotherapy. RESULTS: Acute nausea was prevented completely in 48.5% of the patients in group A and in 43.8% of group B; acute vomiting was prevented completely in 69.7% of the patients in group A and in 67.2% of group B. Delayed nausea was prevented completely in 25.8% of the patients in group A and in 28.1% of group B; delayed vomiting was prevented completely in 47.0% of the patients in group A and in 51.6% of group B. No significant differences in complete control of nausea and vomiting showed between group A and group B (P > 0.05). Both antiemetic regimens were well tolerated, and no difference in adverse events between the 2 groups was observed (P > 0.05). CONCLUSION: China-made tropisetron hydrochloride is as effective as Navoban in the prevention of chemotherapy-induced nausea and vomiting, and only causes mild, infrequent side effects.

Efficacy of progressive muscle relaxation training and guided imagery in reducing chemotherapy side effects in patients with breast cancer and in improving their quality of life.

GOALS: This study was designed to assess the effectiveness of progressive muscle relaxation training (PMRT) and guided imagery (GI) in reducing the anticipatory nausea and vomiting (ANV) and postchemotherapy nausea and vomiting (PNV) of patients with breast cancer and to measure their effects on the patients' quality of life (QoL). PATIENTS AND METHODS: Thirty chemotherapy-naive patients with breast cancer were randomized to the PMRT and GI group and 30 to the control group. Before each of six cycles of adjuvant chemotherapy, each patient was administered a self-report Multiple Affect Adjective Checklist (MAACL), and incidents of ANV and PNV for the first three postchemotherapy days were recorded. All patients were administered the Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and after 3 and 6 months. RESULTS: We found that the PMRT and GI group was significantly less anxious, depressive, and hostile than the control group. We also found that the PMRT and GI group experienced significantly less ANV and PNV and that 6 months after CT, the QoL of the PMRT and GI group was higher than that of the control group. CONCLUSION: These results indicate that PMRT and GI were associated with both the improvements in ANV and PNV and in the QoL of patients with breast cancer.