miércoles, 6 de noviembre de 2019

Treatment-Related Nausea and Vomiting (PDQ®) 2/2 –Health Professional Version - National Cancer Institute

Treatment-Related Nausea and Vomiting (PDQ®)–Health Professional Version - National Cancer Institute

National Cancer Institute

Treatment-Related Nausea and Vomiting (PDQ®)–Health Professional Version

Radiation-Induced Nausea and Vomiting



Introduction

Radiation therapy (RT) is an important cause of nausea and vomiting (N&V) in the cancer patient. Observational studies suggest an 80% overall cumulative incidence rate of some degree of N&V among patients undergoing RT.[1] Risk factors for developing N&V are known. Radiation-induced N&V (RINV) worsens quality of life, leading to treatment delays and cancelled appointments, compromising cancer control.[2,3]

Epidemiology

Two large prospective observational studies provide information on the frequency of RINV and antiemetic measures. The Italian Group for Antiemetic Research in Radiotherapy analyzed the incidence of RINV in 1,020 patients receiving various kinds of radiation therapy.[4] Overall, nausea, vomiting, or both were reported by 28% of patients. The median time to the first episode of vomiting was 3 days. Antiemetic drugs were administered to 17% of the patients, including 12% treated prophylactically and 5% given rescue therapy. In a second cohort of 368 patients receiving RT, the overall incidence rate for nausea was 39% and for vomiting, 7%.[5] Nausea was more frequent in those receiving RT to the lower abdomen or pelvis (66%) compared with patients receiving RT to the head-and-neck area (48%). Antiemetics during RT are underprescribed.[6]

Pathophysiology

The pathophysiology of RINV is incompletely understood. Serotonin, substance P, and dopamine are neurotransmitters involved in radiation-induced emesis.[7] RINV bears a close similarity to chemotherapy-induced N&V (CINV). The effectiveness of serotonin antagonists in RINV supports a role for serotonin in radiation-induced emesis.[7] Substance P antagonists have not been used in RINV as extensively as they are in CINV. Preclinical work suggests a role for substance P in RINV.[8] Substance P antagonists are only beginning to be studied for RINV. Substance P may play a role in prolonged N&V after the administration of RT.

Risk Stratification

Radiation site, volume, fractionation schedule, and single and total dose determine the incidence and severity of RINV. The most important factor appears to be the radiation field. Table 4 shows risk categories suggested by the Multinational Association of Supportive Care in Cancer (MASCC), the European Society for Medical Oncology (ESMO), and the American Society of Clinical Oncology (ASCO).[9] Risk of nausea is not considered in the classification.[10] The risk of N&V for a patient being treated with RT depends on multiple other factors in addition to the emetogenicity of the specific RT regimen. Patient-specific factors include the simultaneous administration of chemotherapy, age, gender, alcohol consumption, anxiety, and previous experience of RINV or CINV.[3]
Table 4. Risk Classification for RINVa
Emetogenic PotentialRisk of Emesis Without Prophylaxis (%)Location
RINV = radiation-induced nausea and vomiting; TBI = total body irradiation.
aAdapted from Roila et al.[3]
High>90TBI
Moderate60–90Upper-abdominal irradiation, craniospinal
Low30–60Cranium (all), head and neck, thorax region, pelvis
Minimal<30Breast, extremities

Treatment

The body of literature describing treatments for RINV is much smaller than that for CINV.[11] Most of the studies done were for patients with moderate- to high-risk features for RINV.

Antiemetic therapy: prevention and treatment of N&V

Several studies show the superiority of serotonin antagonists for the prophylaxis of RINV.[12-17] Ondansetron and dolasetron showed superiority over placebo or metoclopramide. Dosing of the serotonin antagonists have been single-dose pretreatment or for consecutive days (up to 5–7 days total). Most studies have been conducted in patients at moderate to high risk of RINV.
Recommended dosing is ondansetron 8 mg, regardless of schedule given.[3] Granisetron dosing is 2 mg orally per day.[3] A recent meta-analysis covering nine clinical trials showed differing rates of control when emesis versus nausea is considered. Compared with placebo, fewer patients had residual emesis (40% vs. 57%; relative risk [RR], 0.7), and fewer patients required rescue medication (6.5% vs. 36%; RR, 0.18).[18] The control of nausea seems to be more difficult. Most patients developed RT-induced nausea despite treatment (70% vs. 83% with placebo; RR, 0.84).[19] In summary, these trials show that patients receiving upper-abdomen irradiation have a greater benefit using 5-hydroxytryptamine-3 (5-HT3) receptor antagonists than metoclopramide, phenothiazines, or placebo to control RINV.[12-17]
The adverse effects of 5-HT3 receptor antagonists are generally mild, consisting mainly of headache, constipation, and asthenia.[20] Randomized trials in RINV have examined the use of different 5-HT3 receptor antagonists. There are no data comparing those different 5-HT3 receptor antagonists, and there is no consensus on optimal dosing for RINV.[21] A systematic review including 25 randomized and nonrandomized trials revealed that 5-HT3 receptor antagonists were most commonly administered for the entire duration of a course of RT. Optimal duration and timing of 5-HT3 use before, during, and after the administration of RT needs to be determined.[22] With regard to palonosetron, the appropriate dosing and frequency in the RINV setting are still unclear, with once-weekly dosing possible when the drug is combined with other agents.[23]

Corticosteroids

Corticosteroids are an attractive therapeutic antiemetic option because of their widespread availability and low cost. For short-term use, the side effects are few and do not outweigh the benefit of these agents. One randomized trial showed that dexamethasone was significantly more effective than placebo in patients receiving RT to the upper abdomen.[24] Combining corticosteroids with a 5-HT3 receptor antagonist was assessed in a well-designed randomized trial in which a 5-day course of dexamethasone plus ondansetron was compared with ondansetron plus placebo in 211 patients who received RT to the upper abdomen.[25] During the first 5 days, there was a statistically nonsignificant trend toward complete control of nausea (50% vs. 38% with placebo) and vomiting (78% vs. 71%), which was the primary objective of the trial. The effects of dexamethasone extended beyond the initial 5-day period, and significantly more patients had complete control of emesis over the entire course of RT (23% vs. 12% with placebo), a secondary objective of the trial. The trial demonstrates that the addition of dexamethasone has a modest effect on RINV and is potentially a useful addition to a 5-HT3 receptor antagonist in this setting.[25]

Neurokinin-1 (NK-1) receptor antagonists

NK-1 receptor antagonists have an established role in the management of CINV; however, no studies have evaluated the impact of this drug class solely on the risk of RINV. Although preclinical data indicate that RINV is mediated in part by substance P,[8] recommendation of these agents is premature. Therefore, NK-1 receptor antagonists are not reflected in the antiemetic guidelines for RINV.[3] A phase III, randomized, placebo-controlled trial compared an NK-1 receptor antagonist, fosaprepitant, together with palonosetron and dexamethasone, with palonosetron and dexamethasone alone in the prevention of N&V in patients who received concomitant radiation therapy and cisplatin.[23][Level of evidence: I] Patients received fractionated radiation therapy with weekly cisplatin, 40 mg/m2. All patients received dexamethasone on the same schedule: 16 mg on day 1, 8 mg twice a day on day 2, 4 mg twice a day on day 3, and 4 mg once on day 4. More patients who received the three-drug regimen reached a complete response: 48.7% for the placebo group and 65.7% for the fosaprepitant group.
Fosaprepitant has also been compared with olanzapine for the prevention of N&V in patients with head and neck or esophageal cancer who received radiation therapy concurrently with highly emetogenic chemotherapy.[26] For those who received olanzapine, palonosetron, and dexamethasone (OPD), dosing was as follows: dexamethasone 20 mg and palonosetron 0.25 mg intravenously (IV) on day 1 of chemotherapy; and olanzapine 10 mg on days 1 to 4 of chemotherapy. For those who received fosaprepitant, palonosetron, and dexamethasone (FPD), dosing was as follows: dexamethasone 12 mg, palonosetron 0.25 mg IV, and fosaprepitant 150 mg IV on day 1 of chemotherapy, followed by dexamethasone 4 mg bid on days 2 to 3 of chemotherapy. Complete response was similar between the two groups, with a rate of 76% overall in the OPD arm and 74% overall in the FPD arm. This suggests that NK-1 receptor antagonists may play a role in patients receiving highly emetogenic chemotherapy.[26]

Other agents

Older, less-specific antiemetic drugs such as prochlorperazine, metoclopramide, and cannabinoids have shown limited efficacy in the prevention or treatment of RINV, although they may have a role in treating patients with milder symptoms and as rescue agents.[27]

Duration of Prophylaxis

The appropriate duration of antiemetic prophylaxis for patients receiving fractionated RT is not clear. There have been no randomized trials using 5-HT3 receptor antagonists that compared a 5-day course of treatment with a more protracted course.[7] A systematic review that included 25 randomized and nonrandomized trials revealed that 5-HT3 receptor antagonists were most commonly administered for the entire duration of a course of RT.[22] Despite a lack of evidence, the current National Comprehensive Cancer Network guidelines recommend that the decision about whether to continue antiemetic prophylaxis beyond the first week should be based on an assessment of the risk of emesis and relevant individual factors.[28]

Rescue Therapy

The benefit of 5-HT3 receptor antagonists once nausea or vomiting occurs has been suggested in all studies, but there are no trials specifically in this setting.[29] The emerging role of olanzapine in breakthrough emesis in patients with CINV has not been studied in RINV.[30]

Guidelines and Patient Management

For patients at high risk of developing RINV, prophylaxis with a 5-HT3 receptor antagonist is recommended in the clinical practice guidelines from both MASCC and ASCO. On the basis of results from patients receiving highly emetogenic chemotherapy, the addition of dexamethasone to the 5-HT3 receptor antagonist is suggested. The antiemetic clinical practice guidelines from both MASCC and ASCO recommend that patients receiving moderately emetogenic RT be administered prophylaxis with a 5-HT3 receptor antagonist, with or without a short course of dexamethasone.[7] There are no fully published comparative clinical trials on the use of NK-1 receptor antagonists in preventing RINV; therefore, its use cannot be recommended.
Antiemetic dosing suggestions for the prevention of RINV are summarized in Table 5.
Table 5. Antiemetic Dosing for Radiation Therapya
Drug CategoryAntiemeticDoseCommentReference
5-HT3 = 5-hydroxytryptamine-3; bid = twice a day; IV = intravenously; PO = by mouth; prn = as needed; RT = radiation therapy; TBI = total-body irradiation; tid = 3 times a day.
aAdapted from Roila et al.[3] and Hesketh et al.[31]
Serotonin (5-HT3) receptor antagonistsGranisetron2 mg PO daily[16][Level of evidence: I]
Ondansetron8 mg PO or 0.15 mg/kg IV dailybid-tid with TBI[21][Level of evidence: I]
Palonosetron0.25 mg IV or 0.5 mg PONot studied in RT; no data available on frequency of administration[31]
Dolasetron100 mg PO only[13][Level of evidence: I]
CorticosteroidsDexamethasone4 mg PO or IVDuring fractions 1–5[25][Level of evidence: I]
Dopamine receptor antagonistsMetoclopramide20 mg POprn during minimal-emetic-risk RT; inferior to 5-HT3 receptor antagonists[21][Level of evidence: I]
Prochlorperazine10 mg PO or IVprn during minimal-emetic-risk RT[31]


References
  1. Dennis K, Maranzano E, De Angelis C, et al.: Radiotherapy-induced nausea and vomiting. Expert Rev Pharmacoecon Outcomes Res 11 (6): 685-92, 2011. [PUBMED Abstract]
  2. Maranzano E: Radiation-induced emesis: a problem with many open questions. Tumori 87 (4): 213-8, 2001 Jul-Aug. [PUBMED Abstract]
  3. Roila F, Molassiotis A, Herrstedt J, et al.: 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 27 (suppl 5): v119-v133, 2016. [PUBMED Abstract]
  4. Maranzano E, De Angelis V, Pergolizzi S, et al.: A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres. Radiother Oncol 94 (1): 36-41, 2010. [PUBMED Abstract]
  5. Enblom A, Bergius Axelsson B, Steineck G, et al.: One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient. Support Care Cancer 17 (1): 23-32, 2009. [PUBMED Abstract]
  6. Horiot JC: Prophylaxis versus treatment: is there a better way to manage radiotherapy-induced nausea and vomiting? Int J Radiat Oncol Biol Phys 60 (4): 1018-25, 2004. [PUBMED Abstract]
  7. Feyer P, Jahn F, Jordan K: Radiation induced nausea and vomiting. Eur J Pharmacol 722: 165-71, 2014. [PUBMED Abstract]
  8. Yamamoto K, Nohara K, Furuya T, et al.: Ondansetron, dexamethasone and an NK1 antagonist block radiation sickness in mice. Pharmacol Biochem Behav 82 (1): 24-9, 2005. [PUBMED Abstract]
  9. Hesketh PJ, Bohlke K, Lyman GH, et al.: Antiemetics: American Society of Clinical Oncology Focused Guideline Update. J Clin Oncol 34 (4): 381-6, 2016. [PUBMED Abstract]
  10. Feyer PCh, Maranzano E, Molassiotis A, et al.: Radiotherapy-induced nausea and vomiting (RINV): antiemetic guidelines. Support Care Cancer 13 (2): 122-8, 2005. [PUBMED Abstract]
  11. Chow E, Meyer RM, Ding K, et al.: Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol 16 (15): 1463-72, 2015. [PUBMED Abstract]
  12. Aass N, Håtun DE, Thoresen M, et al.: Prophylactic use of tropisetron or metoclopramide during adjuvant abdominal radiotherapy of seminoma stage I: a randomised, open trial in 23 patients. Radiother Oncol 45 (2): 125-8, 1997. [PUBMED Abstract]
  13. Bey P, Wilkinson PM, Resbeut M, et al.: A double-blind, placebo-controlled trial of i.v. dolasetron mesilate in the prevention of radiotherapy-induced nausea and vomiting in cancer patients. Support Care Cancer 4 (5): 378-83, 1996. [PUBMED Abstract]
  14. Volk A, Kersting S, Konopke R, et al.: Surgical therapy of intrapancreatic metastasis from renal cell carcinoma. Pancreatology 9 (4): 392-7, 2009. [PUBMED Abstract]
  15. Franzén L, Nyman J, Hagberg H, et al.: A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 7 (6): 587-92, 1996. [PUBMED Abstract]
  16. Lanciano R, Sherman DM, Michalski J, et al.: The efficacy and safety of once-daily Kytril (granisetron hydrochloride) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy. Cancer Invest 19 (8): 763-72, 2001. [PUBMED Abstract]
  17. Priestman TJ, Dunn J, Brada M, et al.: Final results of the Royal College of Radiologists' trial comparing two different radiotherapy schedules in the treatment of cerebral metastases. Clin Oncol (R Coll Radiol) 8 (5): 308-15, 1996. [PUBMED Abstract]
  18. Priestman TJ, Roberts JT, Upadhyaya BK: A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy. Clin Oncol (R Coll Radiol) 5 (6): 358-63, 1993. [PUBMED Abstract]
  19. Chow E, Zeng L, Salvo N, et al.: Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol) 24 (2): 112-24, 2012. [PUBMED Abstract]
  20. Goodin S, Cunningham R: 5-HT(3)-receptor antagonists for the treatment of nausea and vomiting: a reappraisal of their side-effect profile. Oncologist 7 (5): 424-36, 2002. [PUBMED Abstract]
  21. Salvo N, Doble B, Khan L, et al.: Prophylaxis of radiation-induced nausea and vomiting using 5-hydroxytryptamine-3 serotonin receptor antagonists: a systematic review of randomized trials. Int J Radiat Oncol Biol Phys 82 (1): 408-17, 2012. [PUBMED Abstract]
  22. Dennis K, Nguyen J, Presutti R, et al.: Prophylaxis of radiotherapy-induced nausea and vomiting in the palliative treatment of bone metastases. Support Care Cancer 20 (8): 1673-8, 2012. [PUBMED Abstract]
  23. Ruhlmann CH, Christensen TB, Dohn LH, et al.: Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol 17 (4): 509-18, 2016. [PUBMED Abstract]
  24. Kirkbride P, Bezjak A, Pater J, et al.: Dexamethasone for the prophylaxis of radiation-induced emesis: a National Cancer Institute of Canada Clinical Trials Group phase III study. J Clin Oncol 18 (9): 1960-6, 2000. [PUBMED Abstract]
  25. Wong RK, Paul N, Ding K, et al.: 5-hydroxytryptamine-3 receptor antagonist with or without short-course dexamethasone in the prophylaxis of radiation induced emesis: a placebo-controlled randomized trial of the National Cancer Institute of Canada Clinical Trials Group (SC19). J Clin Oncol 24 (21): 3458-64, 2006. [PUBMED Abstract]
  26. Navari RM, Nagy CK, Le-Rademacher J, et al.: Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting. J Community Support Oncol 14 (4): 141-7, 2016. [PUBMED Abstract]
  27. Roila F, Herrstedt J, Gralla RJ, et al.: Prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: guideline update and results of the Perugia consensus conference. Support Care Cancer 19 (Suppl 1): S63-5, 2011. [PUBMED Abstract]
  28. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Antiemesis. Version 1.2019. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2019. Available online with free registrationExit Disclaimer. Last accessed October 27, 2019.
  29. Mystakidou K, Katsouda E, Linou A, et al.: Prophylactic tropisetron versus rescue tropisetron in fractionated radiotherapy to moderate or high emetogenic areas: a prospective randomized open label study in cancer patients. Med Oncol 23 (2): 251-62, 2006. [PUBMED Abstract]
  30. Navari RM, Nagy CK, Gray SE: The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer 21 (6): 1655-63, 2013. [PUBMED Abstract]
  31. Hesketh PJ, Kris MG, Basch E, et al.: Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 35 (28): 3240-3261, 2017. [PUBMED Abstract]

Pediatric Chemotherapy-Induced Acute Nausea and Vomiting



Published Pediatric Antiemetic Guidelines for Acute Nausea and Vomiting (N&V)

Chemotherapy-induced N&V (CINV) is an important problem in the pediatric population. As in adults, nausea in children is more of a problem than vomiting. Nausea was identified by parents of children receiving active antineoplastic therapy in Ontario as the fourth most prevalent and bothersome treatment-related symptom in their children.[1] Current approaches to the selection of appropriate and effective measures to prevent CINV are based on an accurate description of the potential of antineoplastic therapies to cause N&V. Current recommendations are based on published guidelines.[2] These recommendations include patients aged 1 month to 18 years. Published recommendations are based on patients naïve to antineoplastic therapy who are about to receive their first course of antineoplastic therapy. Recommendations focus on the prevention of acute CINV (i.e., within 24 hours of administration of an antineoplastic agent).
Guidelines recommend that optimal control of acute CINV be defined as no vomiting, no retching, no nausea, no use of antiemetic agents other than those given for CINV prevention, and no nausea-related change in the child’s usual appetite and diet. This level of CINV control is to be achieved on each day that antineoplastic therapy is administered and for 24 hours after administration of the last agent in the antineoplastic therapy cycle.

Emetic Risk

In children receiving antineoplastic agents who were not given antiemetic prophylaxis or who were given prophylaxis known to be ineffective, expected rates of complete CINV control were as follows: high emetic risk, less than 10%; moderate emetic risk, 10% to less than 30%; low emetic risk, 30% to less than 90%; and minimal emetic risk, more than 90%.[2] The expected rate of complete CINV control in children receiving modern antiemetic prophylaxis (5-hydroxytryptamine-3 [5-HT3] antagonist with or without dexamethasone) is more than 70% to 80%.[2] Each chemotherapy agent carries an inherent risk of causing emesis, which is the first issue to be considered in the assessment of an individual’s risk when planning treatment with chemotherapy. Refer to Table 3 for more information about the prevention of acute or delayed CINV.

Antiemetic Prophylaxis

Highly emetogenic chemotherapy

Guidelines [2,3] recommend that children aged 12 years and older who are receiving antineoplastic agents of high emetic risk that are not known or suspected to interact with aprepitant receive aprepitant plus a 5-HT3 antagonist plus dexamethasone. Children who cannot receive dexamethasone should receive a 5-HT3 antagonist plus aprepitant. Children who cannot receive aprepitant should receive a 5-HT3 antagonist plus dexamethasone.

Moderately emetogenic chemotherapy

Children receiving antineoplastic agents of moderate emetogenicity should receive ondansetron, granisetron, or palonosetron plus dexamethasone. Children who cannot receive dexamethasone should receive 5-HT3 antagonist plus aprepitant.[3]

Low emetogenic chemotherapy

Children receiving antineoplastic agents of low emetogenicity should receive a 5-HT3 antagonist.[3]

Minimal emetogenic potential

Children receiving antineoplastic agents of low emetogenicity should receive no routine prophylaxis.[3]

Other Antiemetic Modalities

Current consensus is that acupuncture, acupressure, guided imagery, music therapy, progressive muscle relaxation, and psychoeducational support and information may be effective in children receiving antineoplastic agents.[2] Virtual reality may convey benefit. Other recommendations (low level of evidence) include eating smaller, more-frequent meals; reducing food aromas and other stimuli with strong odors; avoiding foods that are spicy, fatty, or highly salty; taking antiemetics before meals so that the effect is present during and after meals; and using measures and foods (e.g., “comfort foods”) that helped to minimize nausea in the past. Despite a lack of strong evidence, most experts feel that these recommendations are unlikely to result in undesirable effects or to adversely affect quality of life and may convey benefit.

Antiemetics

Prophylaxis with a 5-HT3 antagonist alone leads to poor CINV control in patients receiving antineoplastic agents of moderate and high emetic risk. A synthesis of the three studies that evaluated alternative antiemetic agents (chlorpromazine and metoclopramide) in children receiving highly emetogenic chemotherapy observed a complete CINV control rate of 9% (95% confidence interval: 0, 20).[2] When corticosteroids are contraindicated, it is recommended that nabilone or chlorpromazine be administered together with ondansetron or granisetron to children receiving highly emetogenic chemotherapy. Metoclopramide is a third option for children receiving moderately emetogenic chemotherapy. It is also recommended that corticosteroids be combined with a serotonin antagonist for patients receiving highly and moderately emetogenic chemotherapy.[4]
Antiemetic dosing suggestions for pediatric patients are summarized in Table 6.
Table 6. Pediatric Antiemetic Dosing
ENLARGE
Drug CategoryMedicationDoseAvailable RouteCommentReference
5-HT3 = 5-hydroxytryptamine-3; bid = twice a day; BSA = body surface area; EPS = extrapyramidal symptoms; IM = intramuscular; IV = intravenous; NK-1 = neurokinin-1; PO = oral; PR = rectal; prn = as needed; qd = every day; SL = sublingual; tid = 3 times a day.
aPalonosetron prescribing information lists the pediatric maximum dose at 1.5 mg.
PhenothiazinesChlorpromazine0.5 mg/kg/dose q6h; may increase to 1 mg/kg/dose q6h; maximum dose: 50 mgIVProlongs QTc interval; use with 5-HT3 antagonist when corticosteroid contraindicated; dose adjustments based on efficacy and sedation[5]; [2][Level of evidence: IV]; [6][Level of evidence: I]
Prochlorperazine9–13 kg: 2.5 mg PO qd–bid; maximum dose: 7.5 mg/dPO, IM, IVLess sedation, but increased risk of EPS[5]; [7][Level of evidence: I]
13–18 kg: 2.5 mg PO bid–tid; maximum dose: 10 mg/d
18–39 kg: 2.5 mg tid or 5 mg bid; maximum dose: 15 mg/d
PromethazineAge >2 y: 0.25–1 mg/kg/dose q4–6h; maximum dose: 25 mgPO, IM, IV, PRVesicant[5]
Substituted benzamidesMetoclopramideModerately emetogenic chemotherapy: 1 mg/kg/dose IV once prechemotherapy, then 0.0375 mg/kg/dose PO q6hPO, IM, IVEPS associated with higher doses; pretreat with benztropine or diphenhydramine to prevent EPS; enhances gastric emptying[5]; [8][Level of evidence: I]
Serotonin (5-HT3) receptor antagonistsGranisetron40 μg/kg IV daily; 40 μg/kg PO q12h; maximum: 1 mg/doseIV, PO[9][Level of evidence: I]
OndansetronAge 0–<12 y: 0.15 mg/kg/dose (5 mg/m2/dose) prechemotherapy, then q8h for highly emetogenic or q12h for moderately emetogenic chemotherapyPO, IVAvoid IV doses >16 mg due to QTc prolongation; age >12 y: follow adult dosing[5]; [2][Level of evidence: IV]
Low emetogenic chemotherapy: 0.3 mg/kg/dose (10 mg/m2/dose) once prechemotherapy
Maximum PO dose: 24 mg; maximum IV dose: 16 mg
PalonosetronAge 1 mo–17 y: 20 μg/kg; maximum dose: 0.75 mgaIV, PODue to pediatric half-life of 30 h, administered q2–3d during multiday chemotherapy[2][Level of evidence: I]; maximum dose: [10]
Substance P antagonists (NK-1 receptor antagonists)AprepitantCapsule: Age >12 y: 125 mg prechemotherapy day 1, then 80 mg qd x2 dPOCYP3A4 enzyme inhibitor; CYP2C9 enzyme inducer[11][Level of evidence: I]
Suspension: Age 6 mo–12 y (and >6 kg): 3 mg/kg prechemotherapy day 1, then 2 mg/kg qd x2 dSuspension: Maximum dose day 1: 125 mg; maximum dose days 2–3: 80 mg
FosaprepitantAge 13–17 y: 150 mgIVCYP3A4 enzyme inhibitor; CYP2C9 enzyme inducer[12][Level of evidence: III]
CorticosteroidsDexamethasoneHighly emetogenic chemotherapy: 6 mg/m2/dose q6hPO, IVMay be omitted in some brain tumor, osteosarcoma, and carcinoma protocols due to fear of reducing cytotoxic effects of chemotherapy[5]; [2][Level of evidence: IV]
Moderately emetogenic chemotherapy: BSA ≤0.6 m2: 2 mg q12hCombined with 5-HT3 receptor antagonist
BSA >0.6 m2: 4 mg q12hWhen given with aprepitant or fosaprepitant, reduce dose by 50%
Maximum: 20 mg/doseMost effective for delayed nausea
Methylprednisolone4–10 mg/kg/dosePO, IVGiven with 5-HT3 antagonist[13,14][Level of evidence: I]
BenzodiazepinesLorazepamAnticipatory: 0.02–0.05 mg/kg/dose (maximum: 2 mg/dose) once at bedtime the night before chemotherapy and once prechemotherapyPO, SL, IM, IVMost-commonly used drug in class[5]
Breakthrough: 0.02–0.05 mg/kg/dose IV (maximum: 2 mg) q6h prn[15][Level of evidence: IV]
Atypical antipsychoticsOlanzapine0.1–0.14 mg/kg/dose qd; maximum: 10 mgPO[16][Level of evidence: III]
Other pharmacologic agentsDronabinolAge 6–18 y: 2.1 mg/m2 1–3 h prechemotherapyPOSingle-institution experience only; benefit of appetite stimulant properties[17][Level of evidence: III]
NabiloneAge >4 y:POMay be continued up to 48 h postchemotherapy; has not been compared with 5-HT3 antagonist with or without corticosteroid; use with 5-HT3 antagonist when corticosteroid contraindicated[18][Level of evidence: I]; [7]
<18 kg: 0.5 mg q12h
18–30 kg: 1 mg q12h
>30 kg: 1 mg q8–12h
Maximum dose: 0.06 mg/kg/d

Multiagent single-day chemotherapy regimens

Experience in pediatrics and guidelines recommend basing the emetogenicity of combination antineoplastic regimens on that of the agent of highest emetic risk of many combinations.[19] The emetogenicity of the antineoplastic combinations in the following list appears to be higher than would be appreciated by assessment of the emetic risk of the individual agents.[20]
High Level of Emetic Risk (>90% Frequency of Emesis in Absence of Prophylaxis)
  • Cyclophosphamide + anthracycline.
  • Cyclophosphamide + etoposide.
  • Cytarabine (150–200 mg/m2) + daunorubicin.
  • Cytarabine (300 mg/m2) + etoposide.
  • Cytarabine (300 mg/m2) + teniposide.
  • Doxorubicin + ifosfamide.
  • Doxorubicin + methotrexate (5 g/m2).
  • Etoposide + ifosfamide.


References
  1. Dupuis LL, Milne-Wren C, Cassidy M, et al.: Symptom assessment in children receiving cancer therapy: the parents' perspective. Support Care Cancer 18 (3): 281-99, 2010. [PUBMED Abstract]
  2. Dupuis LL, Boodhan S, Holdsworth M, et al.: Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 60 (7): 1073-82, 2013. [PUBMED Abstract]
  3. Dupuis LL, Sung L, Molassiotis A, et al.: 2016 updated MASCC/ESMO consensus recommendations: Prevention of acute chemotherapy-induced nausea and vomiting in children. Support Care Cancer 25 (1): 323-331, 2017. [PUBMED Abstract]
  4. White L, Daly SA, McKenna CJ, et al.: A comparison of oral ondansetron syrup or intravenous ondansetron loading dose regimens given in combination with dexamethasone for the prevention of nausea and emesis in pediatric and adolescent patients receiving moderately/highly emetogenic chemotherapy. Pediatr Hematol Oncol 17 (6): 445-55, 2000. [PUBMED Abstract]
  5. Lexicomp Online. Hudson, Ohio: Lexi-Comp, Inc., 2019. Available online with subscriptionExit Disclaimer. Last accessed July 15, 2019.
  6. Relling MV, Mulhern RK, Fairclough D, et al.: Chlorpromazine with and without lorazepam as antiemetic therapy in children receiving uniform chemotherapy. J Pediatr 123 (5): 811-6, 1993. [PUBMED Abstract]
  7. Chan HS, Correia JA, MacLeod SM: Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. Pediatrics 79 (6): 946-52, 1987. [PUBMED Abstract]
  8. Köseoglu V, Kürekçi AE, Sarici U, et al.: Comparison of the efficacy and side-effects of ondansetron and metoclopramide-diphenhydramine administered to control nausea and vomiting in children treated with antineoplastic chemotherapy: a prospective randomized study. Eur J Pediatr 157 (10): 806-10, 1998. [PUBMED Abstract]
  9. Berrak SG, Ozdemir N, Bakirci N, et al.: A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy. Support Care Cancer 15 (10): 1163-8, 2007. [PUBMED Abstract]
  10. Kadota R, Shen V, Messinger Y: Safety, pharmacokinetics, and efficacy of palonosetron in pediatric patients: a multicenter, stratified, double-blind, phase 3, randomized study. [Abstract] J Clin Oncol 25 (18 suppl): A-9570, 2007.
  11. Kang HJ, Loftus S, Taylor A, et al.: Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol 16 (4): 385-94, 2015. [PUBMED Abstract]
  12. Siddiqui MA, Ghaznawi HI: Some observations on intestinal parasites in Hajis visiting Saudi Arabia, during 1983 G (1403 H.) Pilgrimage. J Egypt Soc Parasitol 15 (2): 705-12, 1985. [PUBMED Abstract]
  13. Small BE, Holdsworth MT, Raisch DW, et al.: Survey ranking of emetogenic control in children receiving chemotherapy. J Pediatr Hematol Oncol 22 (2): 125-32, 2000 Mar-Apr. [PUBMED Abstract]
  14. Hirota T, Honjo T, Kuroda R, et al.: [Antiemetic efficacy of granisetron in pediatric cancer treatment--(2). Comparison of granisetron and granisetron plus methylprednisolone as antiemetic prophylaxis]. Gan To Kagaku Ryoho 20 (15): 2369-73, 1993. [PUBMED Abstract]
  15. Dupuis LL, Nathan PC: Options for the prevention and management of acute chemotherapy-induced nausea and vomiting in children. Paediatr Drugs 5 (9): 597-613, 2003. [PUBMED Abstract]
  16. Flank J, Thackray J, Nielson D, et al.: Olanzapine for treatment and prevention of acute chemotherapy-induced vomiting in children: a retrospective, multi-center review. Pediatr Blood Cancer 62 (3): 496-501, 2015. [PUBMED Abstract]
  17. Elder JJ, Knoderer HM: Characterization of Dronabinol Usage in a Pediatric Oncology Population. J Pediatr Pharmacol Ther 20 (6): 462-7, 2015 Nov-Dec. [PUBMED Abstract]
  18. Dalzell AM, Bartlett H, Lilleyman JS: Nabilone: an alternative antiemetic for cancer chemotherapy. Arch Dis Child 61 (5): 502-5, 1986. [PUBMED Abstract]
  19. Dupuis LL, Boodhan S, Sung L, et al.: Guideline for the classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 57 (2): 191-8, 2011. [PUBMED Abstract]
  20. Holdsworth MT, Raisch DW, Frost J: Acute and delayed nausea and emesis control in pediatric oncology patients. Cancer 106 (4): 931-40, 2006. [PUBMED Abstract]

Pediatric Delayed Nausea and Vomiting

In adults, delayed nausea and vomiting (N&V) is well documented, and strategies exist to control it. Delayed N&V remains a significant problem despite major improvements in the control of acute N&V and nausea immediately following the administration of chemotherapy. The nature and prevalence of delayed N&V in children after administration of antineoplastic agents have not been well described.[1] Additionally, most pediatric chemotherapy regimens give multiple days of chemotherapy, making the onset and duration of risk for delayed versus acute N&V unclear.
Work in the area of chemotherapy-induced N&V (CINV) in children has been limited in part by the lack of assessment tools and the subjective nature of nausea. In the pediatric population, vomiting is more easily recognizable and measurable than is nausea.[1] Difficulties in assessing nausea in young children may contribute to the common perception that young children experience CINV less frequently than do older children. In addition, caregivers may have a higher tolerance for vomiting in young children and may miss detecting nausea.[1] In view of these limitations, studies often use dietary intake to assess the extent of nausea.
Several investigators have attempted to determine the prevalence of delayed N&V in the pediatric population. Early work suggested a low incidence of delayed N&V.[2] In a large study, the nature and prevalence of delayed CINV in children was assessed.[1] Nausea was self-assessed daily using a numeric scale reflecting the effect of nausea on activities and a faces scale for children aged 3 to 6 years. Diet was also assessed daily. Results showed a 33% incidence of delayed vomiting in patients receiving antineoplastic agents (cyclophosphamide, cisplatin, or carboplatin) and an 11% incidence in those who received other antineoplastic agents. No antiemetics were given on 412 (79%) of 522 study days; nevertheless, 381 (93%) of the 412 study days on which patients did not receive antiemetic support during the delayed phase were completely free from vomiting. Antiemetics were most often given as single agents (ondansetron, on 54 study days; dimenhydrinate, on 17 study days; dexamethasone, on 6 study days). Diet was not affected. The authors concluded that antineoplastic-induced delayed N&V may be less prevalent in children than in adults.[1] The high percentage of children not experiencing delayed vomiting may reflect a lack of significant emetogenic potential among many of the regimens in the study; in 100 of 174 chemotherapy cycles, no antiemetics were administered. In addition, there was no characterization of antiemetic response among moderate and severe chemotherapy regimens.
Another study evaluated the incidence of delayed N&V in pediatric patients receiving moderately and highly emetogenic chemotherapy and also receiving premedications in the form of ondansetron alone or with dexamethasone, depending on a treatment’s emetogenic potential.[3] In this study, investigators measured nausea severity and duration, vomiting severity, the number of vomiting episodes, interference with daily activities by the nausea or vomiting, and assessment of appetite. The authors found that delayed N&V occurred with both moderately and highly emetogenic regimens. The severity of N&V varied between the moderately emetogenic and highly emetogenic chemotherapy regimens. The investigators also found that toddlers had better antiemetic control than did older children, which may be the result of anxiety differences between the age groups. The reasons for greater complete control in the toddler patient population are unclear but are consistent with the authors’ previous study of nausea and vomiting control rates in children.[4] Anxiety and patient perception may be important contributors to N&V in older children; the authors found a relationship between control of acute N&V and the occurrence of delayed N&V.
Another study suggests a higher incidence of delayed N&V.[5] In a sample of pediatric cancer patients (N = 40) receiving chemotherapy, N&V was measured from the child’s perspective using the Adapted Rhodes Index of Nausea and Vomiting for Pediatrics; from the primary caregiver’s perspective using the Adapted Rhodes Index of Nausea and Vomiting for Parents; and among their nurses using the National Cancer Institute Nausea and Vomiting Grading Criteria. The highest frequency of nausea occurred in the delayed period, with 60% of patients (n = 24) having reported delayed nausea. The authors concluded that chemotherapy-induced N&V occurred throughout the chemotherapy course, with delayed N&V occurring most frequently and with greater severity and distress. Delayed N&V in the pediatric population requires further study.
Because well-designed studies on the prevention of delayed N&V in children are not available, no formal recommendation is possible. In the absence of such data, current consensus is to treat children in a manner similar to adults, with appropriately adjusted doses.[6]
References
  1. Dupuis LL, Lau R, Greenberg ML: Delayed nausea and vomiting in children receiving antineoplastics. Med Pediatr Oncol 37 (2): 115-21, 2001. [PUBMED Abstract]
  2. Foot AB, Hayes C: Audit of guidelines for effective control of chemotherapy and radiotherapy induced emesis. Arch Dis Child 71 (5): 475-80, 1994. [PUBMED Abstract]
  3. Holdsworth MT, Raisch DW, Frost J: Acute and delayed nausea and emesis control in pediatric oncology patients. Cancer 106 (4): 931-40, 2006. [PUBMED Abstract]
  4. Small BE, Holdsworth MT, Raisch DW, et al.: Survey ranking of emetogenic control in children receiving chemotherapy. J Pediatr Hematol Oncol 22 (2): 125-32, 2000 Mar-Apr. [PUBMED Abstract]
  5. Rodgers C, Kollar D, Taylor O, et al.: Nausea and vomiting perspectives among children receiving moderate to highly emetogenic chemotherapy treatment. Cancer Nurs 35 (3): 203-10, 2012 May-Jun. [PUBMED Abstract]
  6. Dupuis LL, Sung L, Molassiotis A, et al.: 2016 updated MASCC/ESMO consensus recommendations: Prevention of acute chemotherapy-induced nausea and vomiting in children. Support Care Cancer 25 (1): 323-331, 2017. [PUBMED Abstract]

Pediatric Anticipatory Nausea and Vomiting





Cancer patients who have received chemotherapy may experience nausea and vomiting (N&V) when anticipating chemotherapy. Differences in methodology, timing, and assessment instruments and a focus on nausea or vomiting but not both has led to difficulties in capturing the actual prevalence of anticipatory N&V (ANV) in children. Small study sample sizes preclude capturing the actual frequency of ANV in the pediatric population. Accurate prevalence is also prevented by the use of parent or caregiver proxy reports of nausea and the use of nonvalidated nausea assessment tools.
When ANV was evaluated longitudinally in patients receiving 5-hydroxytryptamine-3 (5-HT3) antagonists and corticosteroids as antiemetic agents, approximately one-third of adults experienced ANV, while anticipatory vomiting was reported in 6% to 11%.[1] A single group of investigators has evaluated ANV in children in the pre–5-HT3 antagonist era. The study reported anticipatory nausea in 23 (29%) of 80 children and anticipatory vomiting in 16 (20%) of 80 children who had received 11 cycles of antineoplastic therapy, on average, before evaluation.[2] In the post–5-HT3 era, the reported prevalence of anticipatory nausea in children has ranged from 0% to 59%.[3] Similar to observations in adult patients, the reported prevalence of anticipatory nausea was always higher than that of anticipatory vomiting, with one exception: one study reported an equivalent prevalence (5 [26%] of 19 patients) for anticipatory nausea and anticipatory vomiting.[4]
This section focuses on the management of ANV in children aged 1 month to 18 years who are receiving antineoplastic medication. Optimal control of ANV is defined as no vomiting, no retching, no nausea, no use of antiemetic agents other than those given for the prevention or treatment of chemotherapy-induced N&V (CINV), and no nausea-related change in the child’s usual appetite and diet. This level of ANV control is to be achieved during the 24 hours before administration of the first antineoplastic agent of the upcoming planned antineoplastic cycle.


Approaches to Prevent ANV in Children

ANV appears to be a conditioned response to CINV experienced in the acute phase (24 hours after administration of chemotherapy) and delayed phase (more than 24 hours after and within 7 days of administration of chemotherapy).[3] The anxiety and distress attendant to CINV reinforce the conditioned response.[3] It follows, therefore, that a higher rate of complete acute and delayed CINV control would result in lower rates of ANV. Adherence to evidence-based guideline recommendations regarding CINV prevention has been shown to substantially improve complete acute CINV control.[5]
Given that ANV appears to be a conditioned response, optimization of acute and delayed CINV control may help minimize exposure to the negative stimuli required for conditioning to occur. Consensus recommendations are that antiemetic interventions be based on published guidelines used for the prevention of acute CINV in children receiving antineoplastic agents,[6] including antineoplastic agent–naïve patients. Once antineoplastic therapy has been initiated, the selection of antiemetic interventions should be informed by evidence-based guidelines and tailored on the basis of the extent of CINV control experienced by the patient and any adverse effects associated with antiemetic agents.

Interventions to Control ANV

Hypnosis

Hypnosis has been defined as an intervention that “provides suggestions for changes in sensation, perception, cognition, affect, mood, or behavior.”[7] Two trials evaluated the role of hypnosis in controlling ANV in children. One study recruited 54 children aged 5 to 17 years who had reported experiencing anticipatory nausea, anticipatory vomiting, or both in a previous study and who were about to receive at least two identical antineoplastic treatment courses.[8] On average, children were 15.8 months (range, 0.5–118 months) from their cancer diagnosis at the time of the study. The control group had received antineoplastic therapy for much longer than the other two groups (29.5 months vs. 8 or 11.5 months).
Although it is not possible to precisely ascertain the emetogenicity of the antineoplastic therapy that the children received, it appears that most received highly emetogenic treatment, as assessed by current classifications of chemotherapy emetogenicity. The antiemetic agents received for prophylaxis were not reported, but children’s antiemetic regimens were unchanged during the trial. The severity of N&V was assessed through semistructured interviews. Children were randomly assigned to receive one of three possible interventions: hypnosis training (imagination-focused therapy), active cognitive distraction (relaxation), or contact with a therapist (control). The authors reported a significant improvement in complete control of anticipatory vomiting in the group who received hypnosis training (12 [57%] of 21 patients at baseline vs. 18 [86%] of 21 patients after hypnosis training; P < .05). Complete control of anticipatory nausea increased from 5 (24%) of 21 patients at baseline to 8 (38%) of 21 patients after hypnosis training.[8]
Another study evaluated hypnosis as a means of preventing ANV in 20 children aged 6 to 18 years who were naïve to chemotherapy.[9] Controls were matched for age (±3 years) and the emetogenicity of their antineoplastic treatment. Insufficient information is available to determine the emetogenicity of the antineoplastic regimens. Children randomly assigned to receive hypnosis did not receive antiemetic prophylaxis but did receive antiemetic agents as needed. Children in the control group received standard antiemetic prophylaxis for 4 to 6 hours after antineoplastic therapy. Ondansetron was given to more children in the control group (7 of 10 patients) than in the hypnosis group (3 of 10 patients).
Children randomly assigned to receive hypnosis were taught self-hypnosis during the initial antineoplastic treatment; children in the control group spent equivalent time in conversation with a therapist. ANV was assessed by means of a daily structured interview with the child. The presence of ANV was assessed at 1 to 2 months, and at 4 to 6 months after diagnosis. At the time of first assessment of ANV, children who had been taught self-hypnosis reported significantly less anticipatory nausea than did the control group, although the incidence was not reported. The rate of anticipatory vomiting was identical in each group (1 of 10 patients). By the time of the second assessment, there was no difference between the groups in the rate of anticipatory nausea. The rate of anticipatory vomiting between the groups was also similar (hypnosis, 0 of 10 patients vs. control, 2 of 10 patients).[9]

Pharmacological interventions

Studies of pharmacologic interventions for ANV have been conducted only in adults and are limited to benzodiazepines. Because patients who experience ANV have been observed to be more anxious than patients who do not experience ANV,[10] anxiolytics have been studied. Studies in adults (two randomized trials) have evaluated the contribution of benzodiazepines as a treatment for ANV.[11,12] Adult cancer patients received placebo or lorazepam 2 mg by mouth the night before antineoplastic treatment, the morning of treatment, and at bedtime for the next 5 days over 180 antineoplastic treatment courses containing cisplatin.[11] Patients also received metoclopramide 2 mg/kg per dose, clemastine, and dexamethasone for antiemetic prophylaxis. At the time of randomization, approximately two-thirds of patients were naïve to antineoplastic agents. ANV was defined as nausea, vomiting, or both that occurred within 12 hours before antineoplastic therapy or 1 hour after the start of antineoplastic therapy. A significantly higher proportion of treatments in which lorazepam was given were associated with complete ANV control, compared with the control group (52% vs. 32%; P < .05). Few adverse effects were attributed to lorazepam; mild sedation occurred in 76% of the patients who received lorazepam and 32% of the control patients.
Women with breast cancer who were naïve to antineoplastic treatment were enrolled in a double-blind placebo-controlled trial comparing the incidence of ANV after relaxation training and either alprazolam (29 patients) or placebo (28 patients). Alprazolam 0.25 mg or placebo was given twice daily by mouth for 6 to 12 months. Triazolam was also given as needed to patients in both study arms to manage insomnia. The proportion of patients who experienced complete control of anticipatory nausea and anticipatory vomiting before the fourth antineoplastic treatment was similar in both study arms (26% vs. 25% and 4% vs. 0%, respectively). Diazepam 5 mg twice daily was given to 29 adult cancer patients with ANV for 3 days before each of four consecutive antineoplastic treatment courses.[12] Thirteen patients (45%) experienced complete ANV control at some time over the four antineoplastic treatment courses.

Conclusions

While the improvement in complete control of ANV provided by psychological interventions such as hypnosis or systematic desensitization may not be dramatic, these interventions may convey benefit to individual patients with minimal risk. For this reason, one guideline development panel recommends that interventions be offered to age-appropriate patients who experience ANV where the expertise and resources exist to deliver them.[6]
Despite the lack of evidence to support the use of benzodiazepines for the treatment of ANV in children, guidelines recommend using lorazepam for ANV in children, based on clinical experience.[13] The recommended initial lorazepam dose was based on current pediatric dosing recommendations, with the usual adult dose as the maximum dose.[14] This dose should be titrated to the needs of each child, with dose lowering recommended for excessive sedation. Guidelines also recommend that dosing be of short duration.[14]


References
  1. Morrow GR, Roscoe JA, Hynes HE, et al.: Progress in reducing anticipatory nausea and vomiting: a study of community practice. Support Care Cancer 6 (1): 46-50, 1998. [PUBMED Abstract]
  2. Dolgin MJ, Katz ER, McGinty K, et al.: Anticipatory nausea and vomiting in pediatric cancer patients. Pediatrics 75 (3): 547-52, 1985. [PUBMED Abstract]
  3. Tyc VL, Mulhern RK, Bieberich AA: Anticipatory nausea and vomiting in pediatric cancer patients: an analysis of conditioning and coping variables. J Dev Behav Pediatr 18 (1): 27-33, 1997. [PUBMED Abstract]
  4. Stockhorst U, Spennes-Saleh S, Körholz D, et al.: Anticipatory symptoms and anticipatory immune responses in pediatric cancer patients receiving chemotherapy: features of a classically conditioned response? Brain Behav Immun 14 (3): 198-218, 2000. [PUBMED Abstract]
  5. Aapro M, Molassiotis A, Dicato M, et al.: The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol 23 (8): 1986-92, 2012. [PUBMED Abstract]
  6. Dupuis LL, Boodhan S, Holdsworth M, et al.: Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 60 (7): 1073-82, 2013. [PUBMED Abstract]
  7. Montgomery GH, Schnur JB, Kravits K: Hypnosis for cancer care: over 200 years young. CA Cancer J Clin 63 (1): 31-44, 2013. [PUBMED Abstract]
  8. Zeltzer LK, Dolgin MJ, LeBaron S, et al.: A randomized, controlled study of behavioral intervention for chemotherapy distress in children with cancer. Pediatrics 88 (1): 34-42, 1991. [PUBMED Abstract]
  9. Jacknow DS, Tschann JM, Link MP, et al.: Hypnosis in the prevention of chemotherapy-related nausea and vomiting in children: a prospective study. J Dev Behav Pediatr 15 (4): 258-64, 1994. [PUBMED Abstract]
  10. Andrykowski MA: The role of anxiety in the development of anticipatory nausea in cancer chemotherapy: a review and synthesis. Psychosom Med 52 (4): 458-75, 1990 Jul-Aug. [PUBMED Abstract]
  11. Malik IA, Khan WA, Qazilbash M, et al.: Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol 18 (2): 170-5, 1995. [PUBMED Abstract]
  12. Razavi D, Delvaux N, Farvacques C, et al.: Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam. J Clin Oncol 11 (7): 1384-90, 1993. [PUBMED Abstract]
  13. van Hoff J, Olszewski D: Lorazepam for the control of chemotherapy-related nausea and vomiting in children. J Pediatr 113 (1 Pt 1): 146-9, 1988. [PUBMED Abstract]
  14. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Antiemesis. Version 1.2019. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2019. Available online with free registrationExit Disclaimer. Last accessed October 27, 2019.

Changes to This Summary (10/30/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Prevention and Management of Acute or Delayed Nausea and Vomiting
Added National Comprehensive Cancer Network 2019 as reference 7.
Added text to state that aprepitant has been shown to be efficacious in preventing nausea and vomiting in breast cancer patients receiving highly emetogenic chemotherapy with cyclophosphamide and doxorubicin (cited Warr et al. as reference 83).
Added Bubalo et al. as reference 84.
Added text about a study comparing granisetron and aprepitant with NEPA, an antiemetic combination of netupitant and palonosetron (cited Zhang et al. as reference 95 and level of evidence I).
Added VARUBI (rolapitant) as reference 98.
Added text to state that there are conflicting data on the efficacy of ginger for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). Also added text about a study of a ginger extract in the management of CINV (cited Bossi et al. as reference 139).
Radiation-Induced Nausea and Vomiting
Added text about a study comparing fosaprepitant with olanzapine for the prevention of nausea and vomiting in patients who received radiation therapy concurrently with highly emetogenic chemotherapy (cited Navari et al. as reference 26).
Added National Comprehensive Cancer Network 2019 as reference 28.
Pediatric Anticipatory Nausea and Vomiting
Added National Comprehensive Cancer Network 2019 as reference 14.
This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary



Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the prevention and control of treatment-related nausea and vomiting in cancer patients. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Treatment-Related Nausea and Vomiting are:
  • Heather C. Justice, MSPAP, PA-C (Milligan College)
  • Alison Palumbo, PharmD, MPH, BCOP (Oregon Health and Science University Hospital)
  • Maria Petzel, RD, CSO, LD, CNSC, FAND (University of TX MD Anderson Cancer Center)
  • Megan Reimann, PharmD, BCOP (Indiana University Health Bloomington)
  • Jason A. Webb, MD, FAPA (Duke University Medical Center)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:
PDQ® Supportive and Palliative Care Editorial Board. PDQ Treatment-Related Nausea and Vomiting. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/nausea/nausea-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389491]
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