To systematically review studies of antiemetics used in the treatment of nausea in patients with far-advanced cancer.
Randomized controlled trials (RCT) and uncontrolled studies identified by electronic and hand searching.
Identified studies were appraised for quality and effect size.
Of 21 studies included, 2 were systematic reviews, 7 were RCT and 12 were uncontrolled studies or case series. Differences in interventions and outcomes amongst the RCT precluded any quantitative data synthesis and all seven studies were prone to bias. Whereas uncontrolled studies indicated a high response rate to standard regimens (75–93% for both nausea and vomiting), RCT showed much lower response rates to these agents (23–36% for nausea, 18–52% for vomiting). The two methods of antiemetic choice (choice based either on the inferred mechanism or empirical) were equally effective. There is reasonably strong evidence for the use of metoclopramide in cancer-associated dyspepsia and steroids in malignant bowel obstruction. There was conflicting evidence about the efficacy of serotonin antagonists compared with standard treatments (e.g. metoclopramide, dopamine antagonists and dexamethasone). There was little or no evidence of the efficacy of some commonly used and seemingly effective drugs such as haloperidol, cyclizine, and methotrimeprazine.
Evidence supporting the existing consensus-based guidelines for management of nausea and vomiting in advanced cancer is sparse. Current approaches to treatment based on the neuropharmacology of the emetic pathway may be inappropriate in this setting. Well-designed studies of the impact of “standard” management and novel agents on nausea and vomiting in palliative populations are needed.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Davis MP, Walsh D (2000) Treatment of nausea and vomiting in advanced cancer. Support Care Cancer 8:444–452
Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Coyle N, Smart-Curley T, Kemeny N, Norton L, Hoskins W, et al (1994) Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res 3:183–189
Mannix KA (1998) Palliation of nausea and vomiting. In: Doyle D, Hanks GWC, Macdonald N (eds) Oxford textbook of palliative medicine, 2nd edn. Oxford University Press, Oxford, pp 489–499
Reuben DB, Mor V (1986) Nausea and vomiting in terminal cancer patients. Arch Intern Med 146:2021–2023
Ashby MA, Fleming BG, Brooksbank M, Rounsefell B, Runciman WB, Jackson K, Muirden N, Smith M (1992) Description of a mechanistic approach to pain management in advanced cancer: preliminary report. Pain 51:153–161
Grunberg SM, Hesketh PJ (1993) Control of chemotherapy-induced emesis. New Engl J Med 329:1790–1796
Peroutka SJ, Snyder SH (1982) Antiemetics: neurotransmitter receptor binding studies predict therapeutic actions. Lancet i:658–659
Bentley A, Boyd K (2001) Use of clinical pictures in the management of nausea and vomiting: a prospective audit. Palliat Med 15:247–253
Lichter I (1993) Which anti-emetic? J Palliat Care 9(1):42–50
Lichter I (1993) Results of anti-emetic management in terminal illness. J Palliat Care 9(2):19–21
Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 354:1896–1900
National Health and Medical Research Council (1999) A guide to the development, implementation and evaluation of clinical practice guidelines. NHMRC, Canberra
Department of Health and Human Services, USA. National Guideline Clearinghouse. www.guideline.gov
Liddle J, Williamson M, Irwig L (1996) Method for evaluating research and guideline evidence. NSW Health Department, Sydney
Finnish Medical Society Duodecim (2001) Nausea and vomiting; causes and treatment alternatives. In: Palliative treatment of cancer. Duodecim Medical Publications, Helsinki
Wilson J, Plourde JY, Marshall D, Yoshida S, Chow W, Harsanyi Z, Pearen S, Darke A (2002) Long-term safety and clinical effectiveness of controlled release metoclopramide in cancer-associated dyspepsia syndrome: a multicenter evaluation. J Palliat Care 18:84–91
Critchley P, Plach N, Grantham M, Marshall D, Taniguchi A, Latimer E (1995) Efficacy of haloperidol in the treatment of nausea and vomiting in the palliative patient: a systematic review (letter). J Pain Symptom Manage 10:521–526
Bruera E, Belzile M, Neumann C, Harsanyi Z, Babul N, Darke A (2000) A double blind crossover study of controlled release metoclopramide and placebo for the chronic nausea and dyspepsia of advanced cancer. J Pain Symptom Manage 19:427–435
Bruera ED, MacEachern TJ, Spachynski KA, LeGatt DF, MacDonald RN, Babul N, Harsanyi Z, Darke AC (1994) Comparison of the efficacy, safety and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer. Cancer 74:3204–3211
Hardy J, Daly S, McQuade B, Albertsson M, Chimontsi-Kypriou V, Stathopoulos GP, Curtin P (2002) A double blind, randomised parallel group, multi-national, multi-centre study comparing single dose ondansetron 24 mg p.o. with placebo and metoclopramide 10 mg tds p.o. in the treatment of opioid induced nausea and emesis in cancer patients. Support Care Cancer 10:231–236
Mystakidou K, Befon S, Liossi C, Vlachos L (1998) Comparison of the efficacy and safety of tropisetron, metoclopramide, and chlorpromazine in the treatment of emesis associated with far advanced cancer. Cancer 83:1214–1223
Mystakidou K, Befon S, Liossi C, Vlachos L (1998) Comparison of tropisetron and chlorpromazine combinations in the control of nausea and vomiting in patients with advanced cancer. J Pain Symptom Manage 15:176–184
Bruera E, Seifert L, Watanabe S, Babul N, Darke A, Harsanyi Z, Suarez-Almazor M (1996) Chronic nausea in advanced cancer patients: a retrospective assessment of a metoclopramide-based antiemetic regimen. J Pain Symptom Manage 11:147–153
Currow DC, Coughlan M, Fardell B, Cooney NJ (1997) Use of ondansetron in palliative medicine. Palliat Med 13:302–307
Jackson WC, Tavernier L (2003) Olanzepine for intractable nausea in palliative care patients. J Palliat Med 6:251–255
Passik SD, Lundberg J, Kirsh KL, Theobald D, Donaghy K, Holtsclaw E, Cooper M, Dugan W (2002) A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manage 23:526–532
Corli O, Cozzolino A, Battaioto L (2001) Effectiveness of levosulpride versus metoclopramide for nausea and vomiting in advanced cancer patients: a double-blind, randomised, cross-over study. J Pain Symptom Manage 22:631–633
Porcel JM, Salud A, Porta J, Schoenenberger JA (1998) Antiemetic efficacy of subcutaneous 5-HT3 receptor antagonists in terminal cancer patients. J Pain Symptom Manage 15:265–266
Twycross R, Bankby G, Hallowood J (1997) The use of low-dose methotrimeprazine (levopromazine) in the management of nausea and vomiting. Prog Palliat Care 5:49–53
Regnard C (1997) Nausea and vomiting—a flow diagram. Palliat Med 1:62–63
Therapeutic Guidelines: Palliative care (2001) Therapeutic Guidelines, Melbourne. http://tg.com.au/home/products/pcg.html
Twycross R, Back I (1998) Nausea and vomiting in advanced cancer. Eur J Palliat Care 5(2):39–45
Feuer DJ, Broadley KE (2003) Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer. Cochrane database of systematic reviews, vol. 1
Hardy J, Ling J, Mansi J, Isaacs R, Bliss J, A’Hern R, Blake P, Gore M, Shepherd J, Hanks G (1998) Pitfalls in placebo-controlled trials in palliative care: dexamethasone for the palliation of malignant bowel obstruction. Palliat Med 12:437–442
Laval G, Giradier J, Laussaniere JM, Leduc B, Haond C, Schaerer R (2000) The use of steroids in the management of inoperable intestinal obstruction in terminal cancer patients: do they remove the obstruction. Palliat Med 14:3–10
Baines M, Oliver DJ, Carter RL (1985) Medical management of intestinal obstruction in patients with advanced malignant disease. A clinical and pathological study. Lancet ii:990–993
Ventafridda V, Ripamonti C, Caraceni A, Spoldi E, Messina L, De Conno F (1990) The management of inoperable gastrointestinal obstruction in terminal cancer patients. Tumori 76:389–393
Fainsinger RL, Spachynski K, Hanson J, Bruera E (1994) Symptom control in terminally ill patients with malignant bowel obstruction (MBO). J Pain Symptom Manage 9:12–18
Gonzalez-Rosales F, Walsh D (1997) Intractable nausea and vomiting due to gastrointestinal mucosal metastases relieved by tetrahydrocannabinol (dronabinol). J Pain Symptom Manage 14:311–314
Mercadente S (1998) Scopolamine butylbromide plus octreotide in unresponsive bowel obstruction. J Pain Symptom Manage 16:278–279
Ripamonti C, Mercadente S (2004) Pathophysiology and management of malignant bowel obstruction. In: Doyle D, Hanks G, Cherny N, Calman K (eds) Oxford textbook of palliative medicine, 3rd edn. Oxford University Press, Oxford, pp 496–507
Bartlett N, Koczwara B (2002) Control of nausea and vomiting after chemotherapy: what is the evidence? Int Med J 32:401–407
Agency for Health Care Policy and Research (1993) Acute pain management: operative or medical procedures and trauma. Clinical Practice Guideline no. 1. AHPCR publication no. 92-0023. US Dept of Health and Human Services, Rockville MD, p 107
Chawla SP, Grunberg SM, Gralla RJ, Hesketh PJ, Rittenberg C, Elmer ME, Schmidt C, Taylor A, Carides AD, Evans JK, Horgan KJ (2003) Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 97:2290–2300
Bruera E, Catz Z, Hooper P, Lentle B, Macdonald N (1987) Chronic nausea and anorexia in patients with advanced cancer: a possible role for autonomic dysfunction (letter). J Pain Symptom Manage 2:19–21
McLeod HL (2002) Genetic strategies to individualize supportive care. J Clin Oncol 22:2765–2767
Rogers JF, Nafziger AN, Bertino JS (2002) Pharmacogenetics affecting dosing, efficacy and toxicity of cytochrome P-450 metabolized drugs. Am J Med 113:746–750
Bernard SA, Bruera E (2000) Drug interactions in palliative care. J Clin Oncol 18:1780–1799
Shoji A, Toda M, Suzuki K, Takahashi H, Takahashi K, Yoshiike Y, Ogura T, Watanuki Y, Nishiyama H, Odagiri S (1999) Insufficient effectiveness of 5-hydroxytryptamine-3 receptor antagonists due to oral morphine administration in patients with cisplatin-induced emesis. J Clin Oncol 17:1926–1930
The study was funded by a Strategic Research Development grant from NHMRC.
About this article
Cite this article
Glare, P., Pereira, G., Kristjanson, L.J. et al. Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far-advanced cancer. Support Care Cancer 12, 432–440 (2004). https://doi.org/10.1007/s00520-004-0629-y
- Advanced cancer
- Systematic review