Advertisement

Supportive Care in Cancer

, Volume 25, Issue 6, pp 2019–2033 | Cite as

A systematic review of methodologies, endpoints, and outcome measures in randomized trials of radiation therapy-induced nausea and vomiting

  • Kristopher Dennis
  • Rehana Jamani
  • Clare McGrath
  • Leila Makhani
  • Henry Lam
  • Patrick Bauer
  • Carlo De Angelis
  • Natalie Coburn
  • C. Shun Wong
  • Edward Chow
Review Article
  • 309 Downloads

Abstract

Purpose

Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features.

Materials and methods

Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures.

Results

From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11–1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported “emetic episode/event” measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., “response,” “control,” “success”) that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori.

Conclusions

Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.

Keywords

Antiemetic Clinical trial Emesis Endpoint Methodology Nausea Outcome Radiation therapy Radiotherapy Retching Systematic review Vomiting 

Notes

Acknowledgements

KD was supported in this work by a Canadian Institutes of Health Research (CIHR) Fellowship Award. The authors are grateful for the support of the Arseneau-Henry Families Research Fund and the Joseph Doyle Research Fund.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare regarding the organizations that sponsored this research. The authors have full control of all primary data and would agree to allow the journal to review it if requested.

References

  1. 1.
    Maranzano E, De Angelis V, Pergolizzi S, Lupattelli M, Frata P, Spagnesi S et al (2010) A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres. Radiother Oncol 94(1):36–41CrossRefPubMedGoogle Scholar
  2. 2.
    The Italian Group for Antiemetic Research in Radiotherapy (1999) Radiation-induced emesis: a prospective observational multicenter Italian trial. Int J Radiat Oncol Biol Phys 44(3):619–625CrossRefGoogle Scholar
  3. 3.
    Olver I, Molassiotis A, Aapro M, Herrstedt J, Grunberg S, Morrow G (2011) Antiemetic research: future directions. Support Care Cancer 19(Suppl 1):S49–S55CrossRefPubMedGoogle Scholar
  4. 4.
    Dennis K, Maranzano E, De Angelis C, Holden L, Wong S, Chow E (2011) Radiotherapy-induced nausea and vomiting. Expert Rev Pharmacoecon Outcomes Res 11(6):685–692CrossRefPubMedGoogle Scholar
  5. 5.
    Feyer PC, Maranzano E, Molassiotis A, Roila F, Clark-Snow RA, Jordan K (2011) Radiotherapy-induced nausea and vomiting (RINV): MASCC/ESMO guideline for antiemetics in radiotherapy: update 2009. Support Care Cancer 19(Suppl 1):S5–S14CrossRefPubMedGoogle Scholar
  6. 6.
    Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR et al (2011) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29(31):4189–4198CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Dennis K, Zhang L, Lutz S, van Baardwijk A, van der Linden Y, Holt T et al (2012) International patterns of practice in the management of radiation therapy-induced nausea and vomiting. Int J Radiat Oncol Biol Phys 84(1):e49–e60CrossRefPubMedGoogle Scholar
  8. 8.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006–1012CrossRefPubMedGoogle Scholar
  9. 9.
    Wu JS, Bezjak A, Chow E, Kirkbride P (2002) Primary treatment endpoint following palliative radiotherapy for painful bone metastases: need for a consensus definition? Clin Oncol (R Coll Radiol) 14(1):70–77CrossRefGoogle Scholar
  10. 10.
    Berry GH, Duncan W, Bowman CM (1971) The prevention of radiation sickness. Report of a double blind random clinical trial using prochlorperazine and metopimazine. Clin Radiol 22(4):534–537CrossRefPubMedGoogle Scholar
  11. 11.
    Mahajan MK, Singh V (1998) Assessment of efficacy of pyridoxine in control of radiation induced sickness. J Indian Med Assoc 96(3):82–83PubMedGoogle Scholar
  12. 12.
    Bodis S, Alexander E 3rd, Kooy H, Loeffler JS (1994) The prevention of radiosurgery-induced nausea and vomiting by ondansetron: evidence of a direct effect on the central nervous system chemoreceptor trigger zone. Surg Neurol 42(3):249–252CrossRefPubMedGoogle Scholar
  13. 13.
    Scarantino CW, Ornitz RD, Hoffman LG, Anderson RF Jr (1994) On the mechanism of radiation-induced emesis: the role of serotonin. Int J Radiat Oncol Biol Phys 30(4):825–830CrossRefPubMedGoogle Scholar
  14. 14.
    Kirkbride P, Bezjak A, Pater J, Zee B, Palmer MJ, Wong R et al (2000) 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):1960–1966CrossRefPubMedGoogle Scholar
  15. 15.
    Wong RK, Paul N, Ding K, Whitehead M, Brundage M, Fyles A et al (2006) 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):3458–3464CrossRefPubMedGoogle Scholar
  16. 16.
    Aass N, Hatun DE, Thoresen M, Fossa SD (1997) 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):125–128CrossRefPubMedGoogle Scholar
  17. 17.
    Abbott B, Ippoliti C, Bruton J, Neumann J, Whaley R, Champlin R (1999) Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant patients receiving chemotherapy and total body irradiation. Bone Marrow Transplant 23(3):265–269CrossRefPubMedGoogle Scholar
  18. 18.
    Belkacemi Y, Ozsahin M, Pene F, Rio B, Sutton L, Laporte JP et al (1996) Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis. Int J Radiat Oncol Biol Phys 36(1):77–82CrossRefPubMedGoogle Scholar
  19. 19.
    Bey P, Wilkinson PM, Resbeut M, Bourdin S, Le Floch O, Hahne W et al (1996) 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):378–383CrossRefPubMedGoogle Scholar
  20. 20.
    Franzen L, Nyman J, Hagberg H, Jakobsson M, Sorbe B, Nyth AL et al (1996) A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 7(6):587–592CrossRefPubMedGoogle Scholar
  21. 21.
    Gibbs SJ, Cassoni AM (1996) A pilot study to evaluate the cost-effectiveness of ondansetron and granisetron in fractionated total body irradiation. Clin Oncol (R Coll Radiol) 8(3):182–184CrossRefGoogle Scholar
  22. 22.
    Henriksson R, Lomberg H, Israelsson G, Zackrisson B, Franzen L (1992) The effect of ondansetron on radiation-induced emesis and diarrhoea. Acta Oncol 31(7):767–769CrossRefPubMedGoogle Scholar
  23. 23.
    Khoo VS, Rainford K, Horwich A, Dearnaley DP (1997) The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in stage I seminoma of the testis: a randomized pilot study. Clin Oncol (R Coll Radiol) 9(4):252–257CrossRefGoogle Scholar
  24. 24.
    Lanciano R, Sherman DM, Michalski J, Preston AJ, Yocom K, Friedman C (2001) The efficacy and safety of once-daily kytril (granisetron hydrochloride) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy. Cancer Investig 19(8):763–772CrossRefGoogle Scholar
  25. 25.
    Logue JP, Magee B, Hunter RD, Murdoch RD (1991) The antiemetic effect of granisetron in lower hemibody radiotherapy. Clin Oncol (R Coll Radiol) 3(5):247–249CrossRefGoogle Scholar
  26. 26.
    Maisano R, Pergolizzi S, Settineri N (1998) Escalating dose of oral ondansetron in the prevention of radiation induced emesis. Anticancer Res 18(3B):2011–2013PubMedGoogle Scholar
  27. 27.
    Morita M, Kuwano H, Ohno S, Kitamura K, Sugimachi K (2000) Antiemetic effect of ramosetron during hyperthermo-chemo-radiotherapy for esophageal cancer. Anticancer Res 20(5C):3631–3636PubMedGoogle Scholar
  28. 28.
    Mystakidou K, Kouloulias V, Nikolaou V, Tsilika E, Lymperopoulou G, Balafouta M et al (2010) A comparative study of prophylactic antiemetic treatment in cancer patients receiving radiotherapy. J BUON 15(1):29–35PubMedGoogle Scholar
  29. 29.
    Okamoto S, Takahashi S, Tanosaki R, Sakamaki H, Onozawa Y, Oh H et al (1996) Granisetron in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study. Bone Marrow Transplant 17(5):679–683PubMedGoogle Scholar
  30. 30.
    Prentice HG, Cunningham S, Gandhi L, Cunningham J, Collis C, Hamon MD (1995) Granisetron in the prevention of irradiation-induced emesis. Bone Marrow Transplant 15(3):445–448PubMedGoogle Scholar
  31. 31.
    Priestman TJ, Roberts JT, Lucraft H, Collis CH, Adams M, Upadhyaya BK et al (1990) Results of a randomized, double-blind comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation. Clin Oncol (R Coll Radiol) 2(2):71–75CrossRefGoogle Scholar
  32. 32.
    Priestman TJ, Roberts JT, Upadhyaya BK (1993) 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):358–363CrossRefGoogle Scholar
  33. 33.
    Sorbe B, Berglind AM (1992) Tropisetron, a new 5-HT3-receptor antagonist, in the prevention of radiation-induced nausea, vomiting and diarrhoea. Drugs 43(Suppl 3):33–39CrossRefPubMedGoogle Scholar
  34. 34.
    Spitzer TR, Bryson JC, Cirenza E, Foelber R, Wallerstadt M, Stout C et al (1994) Randomized double-blind, placebo-controlled evaluation of oral ondansetron in the prevention of nausea and vomiting associated with fractionated total-body irradiation. J Clin Oncol 12(11):2432–2438CrossRefPubMedGoogle Scholar
  35. 35.
    Spitzer TR, Friedman CJ, Bushnell W, Frankel SR, Raschko J (2000) Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation. Bone Marrow Transplant 26(2):203–210CrossRefPubMedGoogle Scholar
  36. 36.
    Sykes AJ, Kiltie AE, Stewart AL (1997) Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy. Support Care Cancer 5(6):500–503CrossRefPubMedGoogle Scholar
  37. 37.
    Tiley C, Powles R, Catalano J, Treleaven J, Eshelby J, Hewetson M et al (1992) Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation. Leuk Lymphoma 7(4):317–321CrossRefPubMedGoogle Scholar
  38. 38.
    Mattie H, Emery EW, Hill ID, Laurence DR (1967) Treatment of radiation sickness with pyridoxine hydrochloride in outpatients of a radiotherapy unit. Br Med J (Clin Res Ed) 3(5559):215–216CrossRefGoogle Scholar
  39. 39.
    Sicher K, Backhouse TW (1968) An assessment of thiethylperazine (Torecan) in the control of radiation-induced nausea and vomiting. Clin Radiol 19(2):238–240CrossRefPubMedGoogle Scholar
  40. 40.
    Cole DR, Duffy DF (1974) Haloperidol for radiation sickness: control of associated nausea, vomiting, and anorexia. N Y State J Med 74(9):1558–1562PubMedGoogle Scholar
  41. 41.
    Mennie AT, Dalley VM, Dinneen LC, Collier HO (1975) Treatment of radiation-induced gastrointestinal distress with acetylsalicylate. Lancet 2(7942):942–943CrossRefPubMedGoogle Scholar
  42. 42.
    Rowlands G, Currie WJ (1976) A trial of valoid (cyclizine) tablets in the control of the nausea and vomiting associated with radiation therapy. Br J Clin Pract 30(10):197–199PubMedGoogle Scholar
  43. 43.
    Stryker JA, Demers LM, Mortel R (1979) Prophylactic ibuprofen administration during pelvic irradiation. Int J Radiat Oncol Biol Phys 5(11–12):2049–2052CrossRefPubMedGoogle Scholar
  44. 44.
    Welch DA (1980) Assessment of nausea and vomiting in cancer patients undergoing external beam radiotherapy. Cancer Nurs 3(5):365–371CrossRefPubMedGoogle Scholar
  45. 45.
    Frytak S, Moertel CG (1981) Management of nausea and vomiting in the cancer patient. JAMA 245(4):393–396CrossRefPubMedGoogle Scholar
  46. 46.
    Lucraft HH, Palmer MK (1982) Randomised clinical trial of levonantradol and chlorpromazine in the prevention of radiotherapy-induced vomiting. Clin Radiol 33(6):621–622CrossRefPubMedGoogle Scholar
  47. 47.
    Budach V (1983) Antiemetic efficacy of alizapride/metoclopramide in cancer radiotherapy-induced nausea and vomiting. Fortschr Med 101(39):1792–1794PubMedGoogle Scholar
  48. 48.
    Ungerleider JT, Andrysiak TA, Fairbanks LA, Tesler AS, Parker RG (1984) Tetrahydrocannabinol vs. prochlorperazine. The effects of two antiemetics on patients undergoing radiotherapy. Radiology 150(2):598–599CrossRefPubMedGoogle Scholar
  49. 49.
    Priestman SG, Priestman TJ, Canney PA (1987) A double-blind randomised cross-over comparison of nabilone and metoclopramide in the control of radiation-induced nausea. Clin Radiol 38(5):543–544CrossRefPubMedGoogle Scholar
  50. 50.
    Bremer K (1991) 5-Hydroxytryptamine (serotonin) subtype 3 antagonists, a major step in prophylaxis and control of cytostatic and radiation-induced emesis. J Cancer Res Clin Oncol 117(1):85–87CrossRefPubMedGoogle Scholar
  51. 51.
    Roberts JT (1992) Ondansetron in the control of refractory emesis following radiotherapy. Clin Oncol (R Coll Radiol) 4(1):67–68CrossRefGoogle Scholar
  52. 52.
    Rosenthal SA, Marquez CM, Hourigan HP, Ryu JK (1992) Ondansetron for patients given abdominal radiotherapy. Lancet 339(8791):490CrossRefPubMedGoogle Scholar
  53. 53.
    Sorbe B, Berglind AM, de Bruijn K (1992) Tropisetron, a new 5-HT3 receptor antagonist, in the prevention of radiation-induced emesis. Radiother Oncol 23(2):131–132CrossRefPubMedGoogle Scholar
  54. 54.
    Sorbe B, Berglind AM, De Bruijn K (1992) Tropisetron, a new 5-HT3 receptor antagonist, in the prevention of irradiation-induced nausea, vomiting and diarrhoea. Eur J Gynaecol Oncol 13(5):382–389PubMedGoogle Scholar
  55. 55.
    LeBourgeois JP, McKenna CJ, Coster B, Feyer P, Franzen L, Goedhals L et al (1999) Efficacy of an ondansetron orally disintegrating tablet: a novel oral formulation of this 5-HT(3) receptor antagonist in the treatment of fractionated radiotherapy-induced nausea and emesis. Clin Oncol (R Coll Radiol) 11(5):340–347CrossRefGoogle Scholar
  56. 56.
    Kim K, Chie EK, Jang JY, Kim SW, Oh DY, Im SA et al (2009) Ramosetron for the prevention of nausea and vomiting during 5-fluorouracil-based chemoradiotherapy for pancreatico-biliary cancer. Jpn J Clin Oncol 39(2):111–115CrossRefPubMedGoogle Scholar
  57. 57.
    Pinkowish MD (2009) Acupressure and acupuncture for side effects of radiotherapy. CA Cancer J Clin 59(5):277–280CrossRefPubMedGoogle Scholar
  58. 58.
    Roscoe JA, Bushunow P, Jean-Pierre P, Heckler CE, Purnell JQ, Peppone LJ et al (2009) Acupressure bands are effective in reducing radiation therapy-related nausea. J Pain Symptom Manag 38(3):381–389CrossRefGoogle Scholar
  59. 59.
    Keats S (2010) High-dose rate brachytherapy in prostate cancer patients—a study on nausea and vomiting. Urol Nurs 30(3):195–202PubMedGoogle Scholar
  60. 60.
    Li GH, Wang DL, Hu YD, Pu P, Li DZ, Wang WD et al (2010) Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy. Med Oncol 27(3):919–925CrossRefPubMedGoogle Scholar
  61. 61.
    Liu C, Cui J, Sun Q, Cai J (2010) Hydrogen therapy may be an effective and specific novel treatment for acute radiation syndrome. Med Hypotheses 74(1):145–146CrossRefPubMedGoogle Scholar
  62. 62.
    Enblom A, Lekander M, Hammar M, Johnsson A, Onelov E, Ingvar M et al (2011) Getting the grip on nonspecific treatment effects: emesis in patients randomized to acupuncture or sham compared to patients receiving standard care. PLoS One 6(3):e14766CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Enblom A, Johnsson A, Hammar M, Onelov E, Steineck G, Borjeson S (2012) Acupuncture compared with placebo acupuncture in radiotherapy-induced nausea—a randomized controlled study. Annals Oncol 23:1353–1361CrossRefGoogle Scholar
  64. 64.
    Emami H, Hematti S, Saeidian SM, Feizi A, Taheri S, Pourya A et al (2015) The efficacy of combination of andansetron and aprepitant on preventing the radiotherapy-induced nausea and vomiting. J Res Med Sci 20(4):329–333PubMedPubMedCentralGoogle Scholar
  65. 65.
    Brown WM (1953) Symptomatic disturbance after single therapeutic dose of x rays; its relationship to the general radiation syndrome. Br Med J (Clin Res Ed) 1(4814):802–805CrossRefGoogle Scholar
  66. 66.
    Chu FC, Paulshock M, Wallenstein SL, Houde RW, Phillips R (1969) A controlled clinical study of metopimazine and perphenazine in treatment of radiation nausea and vomiting. Clin Pharmacol Ther 10(6):800–809CrossRefPubMedGoogle Scholar
  67. 67.
    Parsons JA, Webster JH, Dowd JE (1961) Evaluation of the placebo effect in the treatment of radiation sickness. Acta Radiol 56:129–140CrossRefPubMedGoogle Scholar
  68. 68.
    Ellis F, Stoll BA (1952) Radiation sickness: a clinical investigation. J Fac Radiol 3(3):207–222CrossRefPubMedGoogle Scholar
  69. 69.
    Stoll BA (1957) New drugs for irradiation sickness. Radiology 68(3):380–385CrossRefPubMedGoogle Scholar
  70. 70.
    Solan MJ (1959) Prochlorperazine and irradiation sickness. Br Med J (Clin Res Ed) 2(5159):1068–1069CrossRefGoogle Scholar
  71. 71.
    Kuzma I, Siracka-Vesela E (1960) The application of the antikinetic therapeutic agent “marzine” in the treatment of the radiation sickness. Neoplasma 7:404–407PubMedGoogle Scholar
  72. 72.
    Finney R (1961) “Nidoxital”: a clinical trial. Clin Radiol 12:229–231CrossRefPubMedGoogle Scholar
  73. 73.
    Codiga VA (1961) A new antiemetic for the treatment of nausea and vomiting associated with roentgen therapy. Int Rec Med 174:375–379PubMedGoogle Scholar
  74. 74.
    Cox J, Collins JH (1962) Nausea and vomiting: control by thiethylperazine. Curr Ther Res Clin Exp 4:178–181PubMedGoogle Scholar
  75. 75.
    Jasinski W, Swiecki J, Gajl D (1962) Treatment of radiation sickness with marzine (cyclizine HCl). Pol Przegl Radiol 26:237–239PubMedGoogle Scholar
  76. 76.
    Donovan J (1963) Radiation sickness and its control with thiethylperazine (“torecan”): a preliminary evaluation. Med J Aust 1:614–615PubMedGoogle Scholar
  77. 77.
    Fochem K (1964) On the treatment of radiation syndromes with cyclizine (marezine). Ther Umsch 21:222–224PubMedGoogle Scholar
  78. 78.
    Holt JA (1965) A trial of thiethylperazine (“torecan”) in patients suffering from radiation sickness. Med J Aust 2(7):279–281PubMedGoogle Scholar
  79. 79.
    Johnson EM (1965) The control of radiation sickness with thiethylperazine (torecan). N Z Med J 64(399):649–650PubMedGoogle Scholar
  80. 80.
    Kurohara SS, George FW 3rd, Levitts S, Rubin P (1966) Factor concerned with “clinical radiation nausea”. Radiology 86(2):262–265CrossRefPubMedGoogle Scholar
  81. 81.
    Tornetta FJ (1972) Double-blind evaluation of haloperidol for antiemetic activity. Anesth Analg 51(6):964–967CrossRefPubMedGoogle Scholar
  82. 82.
    Miner WD, Sanger GJ, Turner DH (1987) Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis. Br J Cancer 56(2):159–162CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Collis CH, Priestman TJ, Priestman S, Lucraft H, Roberts JT, Adams M et al (1991) The final assessment of a randomized double-blind comparative study of ondansetron vs. metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation. Clin Oncol (R Coll Radiol) 3:241–242CrossRefGoogle Scholar
  84. 84.
    Clavel M, Soukop M, Greenstreet YL (1993) Improved control of emesis and quality of life with ondansetron in breast cancer. Oncology (Williston Park) 50(3):180–185CrossRefGoogle Scholar
  85. 85.
    Miralbell R, Coucke P, Behrouz F, Blazek N, Melliger M, Philipp S et al (1995) Nausea and vomiting in fractionated radiotherapy: a prospective on-demand trial of tropisetron rescue for non-responders to metoclopramide. Eur J Cancer 31A(9):1461–1464CrossRefPubMedGoogle Scholar
  86. 86.
    Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B (2003) Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 29(6):501–513CrossRefPubMedGoogle Scholar
  87. 87.
    Silverman A, Kligerman MM, Fertig JW, Ellis K (1956) A study of the effectiveness of pyridoxine and dramamine on clinical radiation sickness. Radiology 66(3):403–407CrossRefPubMedGoogle Scholar
  88. 88.
    Finney R (1958) Cortisone and the treatment of radiation sickness. J Fac Radiol 9(2):68–79CrossRefPubMedGoogle Scholar
  89. 89.
    Burwell JA, Wolfson B, Perryman CR, Foldes FF (1961) The use of trimethobenzamide (tigan) for the treatment of radiation induced nausea and emesis. Am J Roentgenol Radium Therapy, Nucl Med 86:752–756Google Scholar
  90. 90.
    Aapro M (1993) Methodological issues in antiemetic studies. Investig New Drugs 11(4):243–253CrossRefGoogle Scholar
  91. 91.
    Hesketh PJ, Gralla RJ, du Bois A, Tonato M (1998) Methodology of antiemetic trials: response assessment, evaluation of new agents and definition of chemotherapy emetogenicity. Support Care Cancer 6(3):221–227CrossRefPubMedGoogle Scholar
  92. 92.
    Morrow GR (1984) Methodology in behavioral and psychosocial cancer research. The assessment of nausea and vomiting. Past problems, current issues and suggestions for future research. Cancer 53(10 Suppl):2267–2280CrossRefPubMedGoogle Scholar
  93. 93.
    Olver IN, Simon RM, Aisner J (1986) Antiemetic studies: a methodological discussion. Cancer Treat Rep 70(5):555–563PubMedGoogle Scholar
  94. 94.
    Olver IN (1996) Antiemetic study methodology: recommendations for future studies. Oncology (Williston Park) 53(Suppl 1):96–101CrossRefGoogle Scholar
  95. 95.
    Tonato M, Roila F, Del Favero A, Ballatori E (1996) Methodology of trials with antiemetics. Support Care Cancer 4(4):281–286CrossRefPubMedGoogle Scholar
  96. 96.
    Multinational Association of Supportive Care in Cancer. MASCC Antiemesis Tool (MAT). Accessed October 4 2016. www.mascc.org/mat.
  97. 97.
    Del Favero A, Roila F, Basurto C, Minotti V, Ballatori E, Patoia L et al (1990) Assessment of nausea. Eur J Clin Pharmacol 38(2):115–120CrossRefPubMedGoogle Scholar
  98. 98.
    Dennis K, Makhani L, Maranzano E, Feyer P, Zeng L, De Angelis C et al (2013) Timing and duration of 5-HT3 receptor antagonist therapy for the prophylaxis of radiotherapy-induced nausea and vomiting: a systematic review of randomized and non-randomized studies. J Radiat Oncol 2(3):271–284CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Division of Radiation OncologyThe Ottawa Hospital and the University of OttawaOttawaCanada
  2. 2.Queen’s UniversityKingstonCanada
  3. 3.Department of Family and Community Medicine, Global Health and Vulnerable PopulationsUniversity of TorontoTorontoCanada
  4. 4.Sunnybrook R. Ian Macdonald Library, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  5. 5.Jagiellonian University Medical CollegeKrakowPoland
  6. 6.Department of Pharmacy, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  7. 7.Division of General Surgery, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  8. 8.Department of Radiation Oncology, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada

Personalised recommendations