Supportive Care in Cancer

, Volume 13, Issue 9, pp 671–678 | Cite as

Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies

  • Petra FeyerEmail author
  • M. Heinrich Seegenschmiedt
  • Maria Steingraeber
Review Article


Radiotherapy-induced nausea and vomiting (RINV) can be one of the most distressing symptoms of radiotherapy treatment, which if incompletely controlled may last for several weeks with fractionated radiotherapy and prevent completion of the planned treatment course. Current treatment guidelines recommend the use of 5-HT3 receptor antagonists with or without corticosteroids for highly and moderately emetogenic radiotherapy, though only granisetron and ondansetron are currently indicated for RINV in most countries. Granisetron is a potent and highly selective 5-HT3 receptor antagonist, with demonstrated efficacy in RINV in both placebo-controlled and comparative studies. In this paper the clinical experience with granisetron in RINV is reviewed, and its efficacy and safety compared with other antiemetic therapies.


Nausea and vomiting Radiotherapy Antiemetic 5-HT3 receptor antagonist Granisetron 



This paper was supported by Hoffmann-La Roche.


  1. 1.
    Aapro M, Bourke JP (2003) Rapid intravenous administration of granisetron prior to chemotherapy is not arrhythmogenic: results of a pilot study. Eur J Cancer 39:927–931PubMedGoogle Scholar
  2. 2.
    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 45:125–128PubMedGoogle Scholar
  3. 3.
    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 23:265–269PubMedGoogle Scholar
  4. 4.
    Abbott B, Ippoliti C, Hecth D, Bruton J, Whaley B, Champlin R (2000) Granisetron (Kytril) plus dexamethasone for antiemetic control in bone marrow transplant patients receiving highly emetogenic chemotherapy with or without total body irradiation. Bone Marrow Transplant 25:1279–1283PubMedGoogle Scholar
  5. 5.
    Belkacemi Y, Ozsahin M, Pene F, 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 36:77–82PubMedGoogle Scholar
  6. 6.
    Bey P, Wilkinson PM, Resbeut M, 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 4:378–383PubMedGoogle Scholar
  7. 7.
    Bloomer JC, Baldwin SJ, Smith GJ, et al (1994) Characterisation of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron. Br J Clin Pharmacol 38:557–566PubMedGoogle Scholar
  8. 8.
    Blower PR (1995) A pharmacologic profile of oral granisetron (Kytril tablets). Semin Oncol 22 [Suppl 10]:3–5Google Scholar
  9. 9.
    Blower PR (2002) 5-HT3-receptor antagonists and the cytochrome P450 system: clinical implications. Cancer J 8:405–414PubMedGoogle Scholar
  10. 10.
    Blower P (2003) Granisetron: relating pharmacology to clinical efficacy. Support Care Cancer 11:93–100PubMedGoogle Scholar
  11. 11.
    Cowan JD, Neidhart J, McClure S, et al (1991) Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst 83:1077–1084PubMedGoogle Scholar
  12. 12.
    Davis MP, Homsi J (2001) The importance of cytochrome P450 monooxygenase CYP2D6 in palliative medicine. Support Care Cancer 9:442–451PubMedGoogle Scholar
  13. 13.
    Dixon CM, Colthup PV, Serabjit-Singh CJ, et al (1995) Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 23:1225–1230PubMedGoogle Scholar
  14. 14.
    Extermann M (2000) Assessment of the older cancer patient. Hematol Oncol Clin North Am 14:63–77PubMedGoogle Scholar
  15. 15.
    Fauser AA, Russ W, Bischoff M (1997) Oral dolasetron mesilate (MDL 73,147EF) for the control of emesis during fractionated total-body irradiation and high-dose cyclophosphamide in patients undergoing allogeneic bone marrow transplantation. Support Care Cancer 5:219–222PubMedGoogle Scholar
  16. 16.
    Feyer PC, Stewart AL, Titlbach OJ (1998) Aetiology and prevention of emesis induced by radiotherapy. Support Cancer Care 6:253–260Google Scholar
  17. 17.
    Freeman AJ, Cunningham KT, Tyers MB (1992) Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action. Anticancer Drugs 3:79–85PubMedGoogle Scholar
  18. 18.
    Franzen L, Nyman J, Hagberg H, et al (1996) A randomized placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 7:587–592PubMedGoogle Scholar
  19. 19.
    Gregory RE, Ettinger DS (1998) 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs 55:173–189PubMedGoogle Scholar
  20. 20.
    Goldberg RM, Mabee J, Chan L, Wong S (1996) Drug–drug interactions in the elderly: analysis of a high risk population. Am J Emerg Med 14:447–450PubMedGoogle Scholar
  21. 21.
    Goshman L, Fish J, Roller K (1999) Clinically significant cytochrome P450 drug interactions. J Pharm Soc Wis 23–38Google Scholar
  22. 22.
    The Italian Group for Antiemetic Research in Radiotherapy (1999) Radiation-induced emesis: a prospective observational multicenter Italian trial. Int J Radiat Oncol Biol Phys 44:619–625Google Scholar
  23. 23.
    Kaiser R, Sezer O, Papies A, et al (2002) Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol 20:2805–2811PubMedGoogle Scholar
  24. 24.
    Kenney WL, Chiu P (2001) Influence of age on thirst and fluid intake. Med Sci Sports Exerc 33:1524–1532PubMedGoogle Scholar
  25. 25.
    Krengli M, Lazzari R, Manara M (1996) Use of orally administered granisetron in radiotherapy-induced emesis (in Italian). Minerva Med 87:605–608PubMedGoogle Scholar
  26. 26.
    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 Invest 19:763–772PubMedGoogle Scholar
  27. 27.
    LeBourgeois JP, McKenna CJ, Coster B, et al (1999) Efficacy of ondansetron orally disintegrating tablet: a novel oral formulation of this 5-HT3 receptor antagonist in the treatment of fractionated radiotherapy-induced nausea and emesis. Clin Oncol 11:340–347Google Scholar
  28. 28.
    Lindley C, Blower P (2000) Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis. Am J Health Syst Pharm 57:1685–1697PubMedGoogle Scholar
  29. 29.
    Logue JP, Magee B, Hunter RD, Murdoch RD (1991) The antiemetic effect of granisetron in lower hemibody radiotherapy. Clin Oncol 3:247–249Google Scholar
  30. 30.
    MASCC Consensus conference on antiemetic therapy, Perugia, 29–31 March 2004. Available at Accessed July 2004
  31. 31.
    Maisano R, Pergolizzi S, Settineri N (1998) Escalating dose of oral ondansetron in the prevention of radiation induced emesis. Anticancer Res 18:2011–2013PubMedGoogle Scholar
  32. 32.
    Miralbell R, Coucke P Behrouz F, 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:1461–1464PubMedGoogle Scholar
  33. 33.
    Okamoto S, Takahashi S, Tanosaki R, et al (1996) Granisetron in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomised study. Bone Marrow Transplant 17:679–683PubMedGoogle Scholar
  34. 34.
    Orchard PJ, Rogosheske J, Burns L, et al (1999) A prospective randomised trial of the anti-emetic efficacy of ondansetron and granisetron during bone marrow transplantation. Biol Blood Marrow Transplant 5:386–393PubMedGoogle Scholar
  35. 35.
    Palmer R (1994) Efficacy and safety of granisetron (Kytril) in two special patient populations: children and adults with impaired hepatic function. Semin Oncol 21 [Suppl 5]:22–25PubMedGoogle Scholar
  36. 36.
    Perez EA, Hesketh P, Sandbach J, et al (1998) Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol 16:754–760PubMedGoogle Scholar
  37. 37.
    Perez EA, Lembersky B, Kaywin P, Kalman L, Yocom K, Friedman C (1998) Comparable safety and antiemetic efficacy of a brief (30-second bolus) intravenous granisetron infusion and a standard (15-minute) intravenous ondansetron infusion in breast cancer patients receiving moderately emetogenic chemotherapy. Cancer J Sci Am 4:52–58PubMedGoogle Scholar
  38. 38.
    Prentice HG, Cunningham S, Gandhi L, Cunningham J, Collis C, Hamon MD (1995) Granisetron in the prevention of irradiation-induced emesis. Bone Marrow Transplant 15:445–448PubMedGoogle Scholar
  39. 39.
    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) 5:358–363Google Scholar
  40. 40.
    Priestman TJ, Roberts JT, Lucraft H, Collis CH, Adams M, Upadhyaya BK, Priestman S (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) 2:71–75Google Scholar
  41. 41.
    Rapoport AP, Meisenberg B, Sarkodee-Adoo C, et al (2002) Autotransplantation for advanced lymphoma and Hodgkin’s disease by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy. Bone Marrow Transplant 29:303–312PubMedGoogle Scholar
  42. 42.
    Reske SN, Bunjes D, Bucmann I, et al (2001) Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation. Eur J Nucl Med 28:807–815PubMedGoogle Scholar
  43. 43.
    Roberts JT, Priestman TJ (1993) A review of ondansetron in the management of radiotherapy-induced emesis. Oncology 50:173–179PubMedGoogle Scholar
  44. 44.
    Roila F, Ciccarese G, Palladino MA, De Angelis V (1998 ) Prevention of radiotherapy-induced emesis. Tumori 84:274–278PubMedGoogle Scholar
  45. 45.
    Rutqvist LE, Lax I, Fornander T, Johansson H (1992) Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Int J Radiat Oncol Biol Phys 22:1157–1158PubMedGoogle Scholar
  46. 46.
    Sanwald P, David M, Dow J (1996) Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos 14:602–609Google Scholar
  47. 47.
    Scarantino CW, Ornitz RO, Hoffman LG, Anderson RF (1994) On the mechanism of radiation-induced emesis: the role of serotonin. Int J Radiat Oncol Biol Phys 30:825–830PubMedGoogle Scholar
  48. 48.
    Schwella N, Konig V, Schwerdtfeger R, et al (1994) Ondansetron for efficient emesis control during total body irradiation. Bone Marrow Transplant 13:169–171PubMedGoogle Scholar
  49. 49.
    Seegenschmiedt MH (2001) Qualitätsmanagement in der radiookolgie. Onkologe 6:291–306Google Scholar
  50. 50.
    Spitzer TR, Bryson JC, Cirenza E, et al (1994) Randomised double-blind placebo-controlled evaluation of oral ondansetron in the prevention of nausea and vomiting associated with fractionated total-body irradiation. J Clin Oncol 12:2432–2438PubMedGoogle Scholar
  51. 51.
    Spitzer TR, Friedman CJ, Bushnell W, Frankel SR, Raschko J (2000) Double-blind randomised, 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 26:203–210PubMedGoogle Scholar
  52. 52.
    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 5:500–503PubMedGoogle Scholar
  53. 53.
    Van Wijngaarden I, Tulp MT, Soudijn W (1990) The concept of selectivity in 5-HT receptor research. Eur J Pharmacol 138:301–302Google Scholar
  54. 54.
    Yancik R, Ries LAG (2000) Aging and cancer in America. Hematol Oncol Clin North Am 14:17–23PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Petra Feyer
    • 1
    Email author
  • M. Heinrich Seegenschmiedt
    • 2
  • Maria Steingraeber
    • 1
  1. 1.Clinic of Radiooncology and Nuclear MedicineVivantes Clinics NeukoellnBerlinGermany
  2. 2.Clinic of RadiooncologyAlfried Krupp HospitalEssenGermany

Personalised recommendations