Nausea and vomiting - randomised controlled trials and other studies

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29 August 2017
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Randomised controlled trials

Double-blind, parallel RCT
Grade 2- moderate

Melhem-Bertrandt A, Munsell M, Fisch M, Morrow P, Lee R, Harden-Harrison M. A randomized, double-blind, placebo-controlled trial of palonosetron plus dexamethasone with or without dronabinol for the prevention of chemotherapy-induced nausea and vomiting after moderately emetogenic chemotherapy, 2014: trial registry entry only at https://clinicaltrials.gov/show/NCT00553059.

62 adult cancer patients aged 29-76 at 4 US sites receiving moderately emetogenic chemotherapy for the first time were randomised to adjuvant treatment of either dronabinol plus palonosetron plus dexamethasone, palonosetron plus dexamethasone or placebo over 5 days.

Double-blind, parallel RCT
Grade 2- moderate

Grunberg SM, Munsell MF, Morrow PKH, Giguere JK, Ule UJ, Saccaro SJ, et al. Randomized double-blind evaluation of dronabinol for the prevention of chemotherapy-induced nausea (abstract only of paper presented at the American Society of Clinical Oncology annual meeting). Journal of Clinical Oncology 2012; 30: 9061.

62 adult cancer patients aged 29-76 receiving chemotherapy who were not habitual cannabinoid users were randomised double-blind to receive dronabinol or placebo as an adjuvant treatment over 5 days.

Double-blind, parallel RCT
Grade 3- low

Duran M, Perez E, Abanades S, Vidal X, Saura C, Majem M, et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology 2010; 70: 656-63.

16 adult cancer patients aged 41-70 with chemotherapy-induced nausea and vomiting were randomised to treatment with nabiximols (Sativex) THC:CBD spray or placebo added to standard anti-emetic treatment over 5 days.

Double-blind, parallel RCT
Grade 2- moderate

Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Current Medical Research and Opinion 2007; 23: 533-43.

64 adult cancer patients aged 24-81 at multiple US sites receiving moderately to highly emetogenic chemotherapy were given adjuvant treatment of either dronabinol, dronabinol in combination with ondansetron, ondansetron, or placebo over 5 days.

Double-blind, parallel RCT
Grade 2- moderate

Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-in-Cachexia-Study-Group. Journal of Clinical Oncology 2006; 24: 3394-400.

164 adult patients with advanced cancer and related weight loss from anorexia with unchanged supportive analgesic, sedative, tranquilliser and anticholergenic treatment from baseline were treated with Swiss pharmaceutical gelatin capsules containing Cannabis sativa plant extracts of 2.5 mg THC and 1 mg CBD, THC only, or placebo over 6 weeks.

Double-blind, parallel RCT
Grade 2- moderate

Jhangiani H, Vredenburgh JJ, Barbato L, Yang HC, Yang HM, Baranowski V, et al. Dronabinol or ondansetron alone and combined for delayed chemotherapy-induced nausea and vomiting (abstract only). Blood 2005; 106: 477B.

64 patients receiving moderate to high emetogenic chemotherapy with a standard antiemetic regimen were randomly assigned to either dronabinol alone, dronabinol in combination with ondansetron, ondansetron alone, or placebo.

Parallel RCT
Grade 2- moderate

Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Annals of Internal Medicine 2003; 139: 258-66.

67 patients with HIV were randomly assigned to treatment with smoked marijuana, dronabinol oral capsules or placebo over 21 days to determine the short-term effects of smoked marijuana on HIV viral load.

Double-blind, parallel RCT
Grade 2- moderate

Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management 1995; 10: 89-97.

139 patients with AIDS-related anorexia aged 22-64 with a mean age of 39 were randomised to receive dronabinol capsules twice daily or placebo over 6 weeks. "Based primarily on this study, dronabinol was approved, under the trademark Marinol, by the Food and Drug Administration (FDA) as a treatment for anorexia associated with weight loss in patients with AIDS. It was the first drug to receive such an indication."

Double-blind, crossover RCT
Grade 3- low

Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, et al. Effect of dronabinol on nutritional status in HIV infection. Annals of Pharmacotherapy 1993; 27: 827-31.

12 HIV positive patients aged 30-48 who had significant weight loss compared dronabinol with placebo in two 5 week periods with a 2 week washout.

Double-blind, parallel RCT
Grade 2- moderate

Lane M, Vogel CL, Ferguson J, Krasnow S, Saiers JL, Hamm J, et al.

Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting. Journal of Pain and Symptom Management 1991; 6: 352-9.

62 adult cancer patients in a multicentre US study aged 20-68 receiving chemotherapy were randomised to receive either dronabinol plus placebo, procholperazine plus placebo, or dronabinol plus procholperazine over 6 days.

Crossover RCT
Grade 3- low

McCabe M, Smith FP, Macdonald JS, Woolley PV, Goldberg D, Schein PS. Efficacy of tetrahydrocannabinol in patients refractory to standard antiemetic therapy. Investigational New Drugs 1988; 6: 243-6.

36 patients aged 18-69 whose vomiting was refractory to standard antiemetic therapy entered this trial to compare THC supplied by US NIDA in oral gelatin capsules with prochlorperazine over two cycles of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Chan HS, Correia JA, MacLeod SM. Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. Pediatrics 1987; 79: 946-52.

30 pediatric cancer patients at the Hospital for Sick Children, Toronto participated in this trial comparing nabilone to prochlorperazine over two cycles of chemotherapy.

Double-blind, parallel RCT
Grade 3- low

Crawford SM, Buckman R. Nabilone and metoclopramide in the treatment of nausea and vomiting due to cisplatinum: a double blind study. Medical Oncology and Tumor Pharmacotherapy 1986; 3: 39-42.

32 cancer patients treated with chemotherapy-induced nausea and vomiting participated in this trial were allocated to receive either oral nabilone or intravenous metoclopramide in random order; only 7 patients completed all 4 planned courses.

Double-blind, parallel RCT
Grade 3- low

Pomeroy M, Fennelly JJ, Towers M. Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis. Cancer Chemotherapy and Pharmacology 1986; 17: 285-8.

38 cancer patients aged 21-66 receiving highly emetogenic chemotherapy regimens were randomised to receive dronabinol or domperidone over 2 chemotherapy cycles.

Double-blind, crossover RCT
Grade 3- low

Dalzell AM, Bartlett H, Lilleyman JS. Nabilone: an alternative antiemetic for cancer chemotherapy. Archives of Disease in Childhood 1986; 61: 502-5.

23 children aged from 1 to 17 receiving repeated identical courses of emetogenic chemotherapy for a variety of malignant diseases compared nabilone to oral domperidone over 2 chemotherapy cycles. 5 patients required additional IV antiemetic treatment during both treatment cycles, 5 other patients required additional antiemetic treatment during the domperidone cycle only.

Crossover RCT
Grade 3- low

Niederle N, Schutte J, Schmidt CG. Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with nonseminomatous testicular cancer receiving cisplatin therapy. Klinische Wochenschrift 1986; 64: 362-5.

20 nonseminomatous testicular cancer patients aged 19-45 not pretreated with emetogenic chemotherapy compared nabilone with alizapride over two courses of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Niiranen A, Mattson K. A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. American Journal of Clinical Oncology 1985; 8: 336-40./

24 lung cancer patients in Finland aged 48-78 receiving cancer chemotherapy compared nabilone with prochlorperazine over two chemotherapy cycles.

Crossover RCT
Grade 2- moderate

Heim ME, Queisser W, Altenburg HP. Randomized crossover study of the antiemetic activity of levonantradol and metoclopramide in cancer patients receiving chemotherapy. Cancer Chemotherapy and Pharmacology 1984; 13: 123-5.

57 cancer patients aged 18-73 receiving chemotherapy with high emetic potential compared levonantranol with metoclopramide over 2 chemotherapy cycles.

Double-blind, parallel RCT
Grade 3- low

Gralla RJ, Tyson LB, Bordin LA, Clark RA, Kelsen DP, Kris MG, et al. Antiemetic therapy: a review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treatment Reports 1984; 68: 163-72.

31 adult cancer patients aged 39-72 undergoing highly emetogenic cancer treatment were randomised to receive dronabinol or metoclopramide.

Double-blind, crossover RCT
Grade 3- low

Sheidler VR, Ettinger DS, Diasio RB, Enterline JP, Brown MD. Double-blind multiple-dose crossover study of the antiemetic effect of intramuscular levonantradol compared to prochlorperazine. Journal of Clinical Pharmacology 1984; 24: 155-9.

20 adult cancer patients at 2 tertiary treatment centres in the US who received chemotherapy compared levonantradol with prochlorperazine.

Parallel RCT
Grade 2- moderate

Hutcheon AW, Palmer JB, Soukop M, Cunningham D, McArdle C, Welsh J, et al. A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy. European Journal of Cancer and Clinical Oncology 1983; 19: 1087-90.

108 patients aged 21-72 at multiple US centres selected to receive combinations of highly emetic cytotoxic chemotherapy for malignant disease were randomly allocated to receive levonantranol at a dose of 2mg per day, 3mg per day, 4mg per day, or prochlorperazine over 24 hours.

Double-blind, crossover RCT
Grade 3- low

George M, Pejovic MH, Thuaire M, Kramar A, Wolff JP. Randomized comparative trial of a new anti-emetic: nabilone, in cancer patients treated with cisplatin. Biomedicine & Pharmacotherapy = Biomedecine & pharmacotherapie 1983; 37: 24-7.

20 patients with a mean age of 54 and advanced gynaecological cancer who received chemotherapy participated in this trial to compare nabilone with chlorpromazine over two cycles of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Kleinman S, Weitzman SA, Cassem N, Andrews E. Double-blind trial of delta-9-tetrahydrocannabinol (THC) versus placebo as an adjunct to prochlorperazine for chemotherapy-induced vomiting. Current Therapeutic Research-Clinical and Experimental 1983; 33: 1014-17.

16 cancer patients with chemotherapy regimens known to cause acute gastrointestinal toxicity compared THC to placebo as an adjunctive treatment.

Double-blind, crossover RCT
Grade 3- low

Ahmedzai S, Carlyle DL, Calder IT, Moran F. Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. British Journal of Cancer 1983; 48: 657-63.

34 cancer patients aged 27-72 receiving highly emetogenic chemotherapy compared nabilone with procholperazine in two four day periods with a four day washout.

Crossover RCT
Grade 2- moderate

Levitt M. Nabilone vs. placebo in the treatment of chemotherapy-induced nausea and vomiting in cancer patients. Cancer Treatment Reviews 1982; 9 Suppl B: 49-53.

58 cancer patients aged 17-78 years, half over 57, with lung, ovarian, breast, and other cancers on chemotherapy, 41 of whom had received cancer chemotherapy previously compared nabilone with placebo over two chemotherapy cycles.

Double-blind, crossover RCT
Grade 2- moderate

Ungerleider JT, Andrysiak T, Fairbanks L, Goodnight J, Sarna G, Jamison K. Cannabis and cancer chemotherapy: a comparison of oral delta-9-THC and prochlorperazine. Cancer 1982; 50: 636-45.

214 adult cancer patients aged 18-82 receiving a course of chemotherapy with a high emetic potential compared oral THC supplied by NIDA with prochlorperazine over two cycles of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Johansson R, Kilkku P, Groenroos M. A double-blind, controlled trial of nabilone vs. prochlorperazine for refractory emesis induced by cancer chemotherapy. Cancer Treatment Reviews 1982; 9 Suppl B: 25-33.

26 adult cancer patients in Finland aged 18-70 years with previous refractory nausea and vomiting compared nabilone with prochlorperazine over 2 cycles of chemotherapy.

Crossover RCT
Grade 3- low

Jones SE, Durant JR, Greco FA, Robertone A. A multi-institutional Phase III study of nabilone vs. placebo in chemotherapy-induced nausea and vomiting. Cancer Treatment Reviews 1982; 9 Suppl B: 45-8.

54 cancer patients aged 20-58 at 3 sites receiving chemotherapy likely to produce nausea and vomiting compared nabilone with placebo over 2 cycles of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Wada JK, Bogdon DL, Gunnell JC, Hum GJ, Gota CH, Rieth TE. Double-blind, randomized, crossover trial of nabilone vs. placebo in cancer chemotherapy. Cancer Treatment Reviews 1982; 9 Suppl B: 39-44.

114 adult patients aged 18-81 in the US taking chemotherapeutic agents likely to cause nausea and vomiting compared nabilone to placebo over 2 cycles of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Long A, Mioduszewski J, Natale R. A randomized double-blind cross-over comparison of the antiemetic activity of levonantradol and prochlorperazine (abstract only). Paper presented at the Proceedings of the Annual Meeting of the American Society of Clinical Oncology; 1982.

42 adult cancer patients aged 20-67 receiving strongly emetic chemotherapy compared levonantradol to prochlorperazine over 2 four week periods with a 2 week washout.

Crossover RCT
Grade 3- low

Broder L, Lean N, Hilsenbeck S. A randomized blinded clinical trial comparing delta-9-tetrahydrocannabinol and hydroxizine as antiemetics for cancer chemotherapy (abstract only). Proceedings of the American Association for Cancer Research; 1982; 23: 514.

44 patients receiving cancer chemotherapy participated in this trial comparing THC to hydroxyzine.

Double-blind,crossover RCT
Grade 2- moderate

Neidhart JA, Gagen MM, Wilson HE, Young DC. Comparative trial of the antiemetic effects of THC and haloperidol. Journal of Clinical Pharmacology 1981; 21: 38S-42S.

52 cancer patients taking chemotherapeutic agents compared THC supplied by the US National Cancer Institute in oral gelatin capsules with haloperidol over two courses of chemotherapy with each agent.

Double-blind, crossover RCT
Grade 2- moderate

Einhorn LH, Nagy C, Furnas B, Williams SD. Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. Journal of Clinical Pharmacology 1981; 21: 64S-69S.

80 patients aged 15-74 receiving combination chemotherapy for neoplastic disease, drug regimens that produce severe nausea and vomiting, were specifically selected for this study comparing nabilone to prochlorperazine over 2 chemotherapy cycles with a three week washout.

Double-blind, crossover RCT
Grade 3- low

Chang AE, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, et al. A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer 1981; 47: 1746-51.

8 patients aged 17-58 with resected soft tissue sarcomas who received adjuvant Adriamycin and Cytoxan chemotherapy compared THC gelatin capsules, marijuana (THC) cigarettes and placebo capsules or cigarettes supplied by US NIDA over a maximum of three paired trials in a randomised sequence.

Double-blind, crossover RCT
Grade 3- low

Orr LE, McKernan JF. Antiemetic effect of delta 9-tetrahydrocannabinol in chemotherapy-associated nausea and emesis as compared to placebo and compazine. Journal of Clinical Pharmacology 1981; 21: 76S-80S.

55 patients harbouring a variety of neoplasms who had previously demonstrated repeated vomiting from chemotherapy agents known to induce emesis compared THC in oral capsules with placebo and with prochlorperazine.

Double-blind, crossover RCT
Grade 3- low

Colls BM. Cannabis and cancer chemotherapy. Lancet 1980; 1: 1187-8.

35 adult cancer patients receiving chemotherapy across three sites compared THC oral capsules supplied by the New Zealand Ministry of Health (4mg per capsule in a lactose base), metoclopramide and thiethylperazine.

Double-blind, crossover RCT
Grade 3- low

Colls BM, Ferry DG, Gray AJ, Harvey VJ, McQueen EG. The antiemetic activity of tetrahydrocannabinol versus metoclopramide and thiethylperazine in patients undergoing cancer chemotherapy. New Zealand Medical Journal 1980; 91: 449-51.

35 adult cancer patients receiving chemotherapy across three sites compared THC oral capsules supplied by the New Zealand Ministry of Health (4mg per capsule in lactose base), metoclopramide and thiethylperazine.

Double-blind, crossover RCT
Grade 3- low

Orr LE, McKernan JF, Bloome B. Antiemetic effect of tetrahydrocannabinol compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. Archives of Internal Medicine 1980; 140: 1431-3.

55 patients with a variety of neoplasms requiring drug therapy who had previously demonstrated repeated vomiting from anticancer agents known to induce emesis compared THC in oral capsules supplied by US NIDA with prochlorperazine and with placebo over 2 chemotherapy cycles.

Double-blind, crossover RCT
Grade 3- low

Sallan SE, Cronin C, Zelen M, Zinberg NE. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. New England Journal of Medicine 1980; 302: 135-8.

85 cancer patients who had previously failed to benefit from standard antiemetics while receiving chemotherapy were randomised to compare dronabinol supplied by US NIDA with prochlorperazine over 3 courses of chemotherapy.

Double-blind, crossover RCT
Grade 3- low

Steele N, Gralla RJ, Braun DW, Jr., Young CW. Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treatment Reports 1980; 64: 219-24.

55 patients aged 19-65 receiving cancer chemotherapy were randomised and 37 completed 2 chemotherapy cycles comparing nabilone with prochlorperazine.

Double-blind, parallel RCT
Grade 2- moderate

Frytak S, Moertel CG, O'Fallon JR, Rubin J, Creagan ET, O'Connell MJ, et al. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo. Annals of Internal Medicine 1979; 91: 825-30.

116 older adult gastrointestinal cancer patients with a median age of 61 undergoing chemotherapy regimes were randomised to receive oral THC, prochlorperazine or placebo.

Parallel RCT
Grade 2- moderate

Frytak S, Moertel CG, Ofallon JR. Comparison of delta-9-tetrahydrocannabinol, prochlorperazine and placebo as anti-emetics for cancer chemotherapy (abstract only). Proceedings of the American Association for Cancer Research; 1979; 20: 391.

117 older adult gastrointestinal cancer patients with a median age of 61 undergoing chemotherapy regimes were randomised to receive oral THC, prochlorperazine or placebo over 4 days.

Double-blind, crossover RCT
Grade 2- moderate

Herman TS, Einhorn LH, Jones SE, Nagy C, Chester AB, Dean JC, et al. Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. New England Journal of Medicine 1979; 300: 1295-7.

113 patients aged 15-74 under treatment for various cancers receiving repeated courses of chemotherapy, all of whom had experienced drug-induced nausea and vomiting, compared nabilone in 1mg capsules with prochlorperazine over 2 chemotherapy cycles.

Double-blind, parallel RCT
Grade 3- low

Chang AE, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation. Annals of Internal Medicine 1979; 91: 819-24.

15 patients aged 15-49 years with osteogenic sarcoma receiving high-dose methotrexate chemotherapy were randomised to receive THC gelatin capsules, marijuana (THC) cigarettes, placebo capsules or placebo cigarettes supplied by US NIDA.

Double-blind, crossover RCT
Grade 3- low

Kluin-Neleman JC, Neleman FA, Meuwissen OJ, Maes RA. Delta 9-Tetrahydrocannabinol (THC) as an antiemetic in patients treated with cancer chemotherapy; a double-blind cross-over trial against placebo. Veterinary and Human Toxicology 1979; 21: 338-40.

11 cancer patients with chemotherapy induced nausea and vomiting compared THC with placebo.

RCT
Grade - unclear

Ekert H, Waters KD, Jurk IH, Mobilia J, Loughnan P. Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Medical Journal of Australia 1979; 2: 657-9.

42 children receiving anticancer chemotherapy compared THC in "brown capsules" supplied by US NIDA with metoclopramide and prochlorperazine.

Double-blind, crossover RCT
Grade 3- low

Sallan SE, Zinberg NE, Frei E, 3rd. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. New England Journal of Medicine 1975; 293: 795-7.

22 adult cancer patients aged 18-76 compared THC supplied by US NIDA in oral gelatin capsules with placebo.

Other studies

Prospective observational study
Grade 2- moderate

Maida V, Ennis M, Irani S, Corbo M, Dolzhykov M. Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. Journal of Supportive Oncology 2008; 6: 119-24.

112 advanced cancer patients given nabilone as an adjunctive treatment were compared to patients not given nabilone.

Case study
Grade 4- very low

Green ST, Nathwani D, Goldberg DJ, Kennedy DH. Nabilone as effective therapy for intractable nausea and vomiting in AIDS. British Journal of Clinical Pharmacology 1989; 28: 494-5.

A gravely ill 52 year old HIV- seropositive man with a cryptosporidial infection was given palliative treatment with nabilone after the failure of more conventional agents to relieve his distress.

Nonrandomized single arm study
Grade unclear

Vinciguerra V, Moore T, Brennan E. Inhalation marijuana as an antiemetic for cancer chemotherapy. New York State Journal of Medicine 1988; 88: 525-7.

74 adult cancer patients refractory to conventional antiemetics entered this trial of marijuana cigarettes supplied by US NIDA to the New York State Department of Health. 56 were evaluable; 18 later withdrew. All patients were instructed on standard smoking procedures.