Skip to main content

Granisetron: is there a dose–response effect on nausea and vomiting?

Cancer Chemotherapy and Pharmacology volume 52, pages 89–98 (2003)Cite this article

Abstract

Purpose

Nausea and vomiting are two of the most debilitating side effects of cytotoxic chemotherapy. Prevention of nausea and vomiting is, thus, very important to ensure that cancer patients continue to receive optimal cytotoxic therapy while seeking to maintain their quality of life. Significant advances in antiemetic therapy have been achieved since the introduction of the 5-HT3 receptor antagonists, and these agents are currently regarded as first-line antiemetic agents. The aim of this article is to examine the hypothesis that there is a dose–response effect of granisetron for preventing chemotherapy-induced nausea and vomiting in cancer patients.

Methods

A literature review of relevant publications was undertaken to provide a comprehensive review of issues related to the control of chemotherapy-induced emesis with escalating doses of granisetron.

Results

There is evidence to suggest that there is a significant trend towards an improved efficacy of granisetron—in both the control of emesis and secondary end-points such as nausea and anorexia—with increasing doses, up to 40 μg/kg, in adults. At this dose, the likelihood of treatment success may be enhanced for most patients regardless of their individual emetogenic risk. Additionally, incremental doses of granisetron (up to 9 mg) have been shown to be effective and well tolerated in patients with refractory emesis.

Conclusions

Those patients experiencing inadequate control of nausea and vomiting following granisetron may also benefit from retreatment with supplementary doses of granisetron, and over subsequent chemotherapy cycles, these patients should receive granisetron 40 μg/kg to ensure emesis protection.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1a, b.
Fig. 2.
Fig. 3.
Fig. 4.

References

  1. Aapro MS, Kirchner V, Terrey JP (1994) The incidence of anticipatory nausea and vomiting after repeat cycle chemotherapy: the effect of granisetron. Br J Cancer 69:957

    CAS  PubMed  Google Scholar 

  2. Addelman M, Erlichman C, Fine S, Warr D, Murray C (1990) Phase I/II trial of granisetron: a novel 5-hydroxytryptamine antagonist for the prevention of chemotherapy-induced nausea and vomiting. J Clin Oncol 8:337

    CAS  PubMed  Google Scholar 

  3. Allen A, Asgill CC, Pierce DM, Upward J, Zussman BD (1994) Pharmacokinetics and tolerability of ascending intravenous doses of granisetron, a novel 5-HT3 antagonist, in healthy human subjects. Eur J Clin Pharmacol 46:159

    CAS  PubMed  Google Scholar 

  4. Andrews PLR, Blower PR (1995) 5-HT3 receptor antagonists and emesis; a pre-clinical review. Pharma Med 13:153

    CAS  Google Scholar 

  5. Andrews PLR, Davis CJ (1993) The mechanism of emesis induced by anti-cancer therapies. In: Andrews PLR, Sanger GJ (eds) Emesis in anticancer therapy, mechanisms and treatment. Chapman & Hall, London, p 14

  6. Andrews PLR, Davis CJ, Bingham S, Davidson HIM, Hawthorn J, Maskell L (1990) The abdominal visceral innervation and the emetic reflex: pathways, pharmacology and plasticity. Can J Physiol Pharmacol 68:325

    CAS  PubMed  Google Scholar 

  7. Andrews P, Bhandari P, Davey P, Bingham S, Marr H, Blower P (1992) Are all 5-HT3 receptor antagonists the same? Eur J Cancer 28A:52

    Google Scholar 

  8. Anzemet (dolasetron mesylate) tablets and injection (1999) Prescribing Information. Hoechst Marion Roussel, Kansas City, MO

  9. ASHP (1999) ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm 56:729

    PubMed  Google Scholar 

  10. Balducci L (2001) A practical approach to the older patient. Curr Probl Cancer 25:6

    CAS  PubMed  Google Scholar 

  11. Baltzer L, Kris MG, Hinkley L, Pisters K, Lacava PV, Pierri MK, Rigas JR, Grant SC, Gralla RJ, Grunberg S, Hahne W (1994) Reversible electrocardiographic interval prolongations following the specific serotonin antagonists ondansetron (OND) and dolasetron mesylate (DM): a possible drug class effect without sequelae? (abstract 1489). Proc Am Soc Clin Oncol 13:433

    Google Scholar 

  12. Beck TM, Hesketh PJ, Madajewicz S, Navari RM, Pendergrass K, Lester EP, Kish JA, Murphy WK, Hainsworth JD, Gandara DR, Bricker LJ, Keller AM, Mortimer J, Galvin DV, House KW, Bryson JC (1992) Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. J Clin Oncol 10:1969

    CAS  PubMed  Google Scholar 

  13. Bentley KR, Barnes NM (1998) 5-Hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated vagus nerve: modulation by trichloroethanol and related alcohols. Eur J Pharmacol 354:25

    Article  CAS  PubMed  Google Scholar 

  14. Bermudez J, Boyle EA, Miner WD, Sanger GJ (1988) The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694. Br J Cancer 58:644

    CAS  PubMed  Google Scholar 

  15. Bingham S, Blower P, Davey P, King P, Sanger G, Wardle K, Nishioka Y (1994) Differences between the anti-emetic efficacies of the 5-HT3 receptor antagonists granisetron and azasetron in the conscious ferret. Pharmacometrics 47:21

    CAS  Google Scholar 

  16. Bleiberg HH, Speilmann M, Falkson G, Romain D (1995) Antiemetic treatment with oral granisetron in patients receiving moderately emetogenic chemotherapy: a dose ranging study. Clin Ther 17:38

    Article  CAS  PubMed  Google Scholar 

  17. Bloomer JC, Baldwin SJ, Smith GJ, Ayrton AD, Clarke SE (1994) Characterisation of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron. Br J Clin Pharmacol 38:557

    CAS  PubMed  Google Scholar 

  18. Blower PR (1995) Differences in anti-emetic predictability among 5-HT3 receptor antagonist drugs. In: Dubois A, King GL, Livengood DR (eds) Radiation and the GI tract. CRC Press, Boca Raton, p 37

  19. Blower PR (1995) A pharmacologic profile of oral granisetron (Kytril tablets). Semin Oncol 22 [Suppl 10]:3

  20. Blower PR (2002) 5-HT3-receptor antagonists and the cytochrome P450 system: clinical implications. Cancer J 8:404

    Google Scholar 

  21. Blower PR (2003) Granisetron: relating pharmacology to clinical efficacy. Support Care Cancer 11:93

    PubMed  Google Scholar 

  22. Blower P, Aapro M (2002) Granisetron vs ondansetron: is it a question of duration of 5-HT3 receptor blockade? Br J Cancer 86:1665

    Google Scholar 

  23. Bonhaus DW, Stefanich E, Loury DN, Hsu SA, Eglen RM, Wong EH (1995) Allosteric interactions among agonists and antagonists at 5-hydroxytryptamine3 receptors. J Neurochem 65:104

    CAS  PubMed  Google Scholar 

  24. Bosnjak SM, Neskovic-Konstantinovic ZB, Jovanovic-Micic DJ, Mitrovic LB, Radulovic SS (1996) Single 8 mg dose of oral ondansetron failed to prevent FAC chemotherapy-induced acute nausea and vomiting. J Chemother 8:315

    CAS  PubMed  Google Scholar 

  25. Bubalo J, Seelig F, Karbowicz S, Maziarz RT (2001) Randomized open-label trial of dolasetron for the control of nausea and vomiting associated with high-dose chemotherapy with hematopoietic stem cell transplantation. Biol Bone Marrow Transplant 7:439

    CAS  Google Scholar 

  26. Carmichael J, Cantwell BMJ, Edwards CM, Zussman BD, Thompson S, Rapeport WG, Harris AL (1989) A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response. Cancer Chemother Pharmacol 24:45

    Google Scholar 

  27. Carmichael J, Phillip PA, Forfar C, Harris AL (1995) An open study to assess the safety, tolerance and pharmacokinetics of an intravenous infusion of granisetron given at 3 mg over 30 s in patients receiving chemotherapy for malignant disease. Cancer Chemother Pharmacol 37:134

    Article  CAS  PubMed  Google Scholar 

  28. Carmichael J, Keizer HJ, Cupissol D, Milliez J, Scheidel P, Schindler AE (1998) Use of granisetron in patients refractory to previous treatment with antiemetics. Anticancer Drugs 9:381

    CAS  PubMed  Google Scholar 

  29. Carney DN (1994) Chemotherapy induced nausea and vomiting. Ir Med J 87:1323

    Google Scholar 

  30. Chin SB, Kucuk O, Peterson R, Ezdinli EZ (1992) Variables contributing to anticipatory nausea and vomiting in cancer chemotherapy. Am J Clin Oncol 15:262

    CAS  PubMed  Google Scholar 

  31. Cooper SM, Arnold BDC, Rapeport WG (1988) Inhibition of 5-HT induced axon-reflex flares by BRL 43694, a novel 5-HT3 receptor antagonist. Br J Clin Pharmacol 25:106

    Google Scholar 

  32. Corcoran ME (1997) Polypharmacy in the older patient with cancer. Cancer Control 4:419

    PubMed  Google Scholar 

  33. Cowan JD, Neidhart J, McClure S, Coltman CA (1991) Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a South-West Oncology Group study. J Natl Cancer Inst 83:1077

    CAS  PubMed  Google Scholar 

  34. de Boer-Dennert M, de Wit R, Schmitz PI, Djontono J, Beurden V, Stoter G, Verweij J (1997) Patient perceptions of the side-effects of chemotherapy: the influence of 5-HT3 antagonists. Br J Cancer 76:1055

    PubMed  Google Scholar 

  35. de Wit R, van den Berg H, Burghouts J, Nortier J, Slee P, Rodenburg C, Keizer J, Fonteyn M, Verweij J, Wils J (1998) Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles. Br J Cancer 77:1487

    PubMed  Google Scholar 

  36. de Wit R, de Boer AC, Linden GHM, Stoter G, Sparreboom A, Verweij J (2001) Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy. Br J Cancer 85:1099

    Article  PubMed  Google Scholar 

  37. Dixon CM, Colthup PV, Serabjit-Singh CJ, Kerr BM, Boehlert CC, Park GR, Tarbit MH (1995) Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 23:1225

    CAS  PubMed  Google Scholar 

  38. Doherty KM (1999) Closing the gap in prophylactic antiemetic therapy: patient factors in calculating the emetogenic potential of chemotherapy. Clin J Oncol Nurs 3:113

    CAS  PubMed  Google Scholar 

  39. Du Bois A (1999) Klinik und management der chemotherapie-induzierten emesis. In: Du Bois A, Feyer P, Ortner P (eds) Emesis in der tumortherapie. Ellyott Medizin Verlag, Hamburg, p 40

  40. Eisele JL, Bertrand S, Galzi JL, Devillers-Thiery A, Changeux JP, Bertrand D (1993) Chimaeric nicotine-serotonergic receptor combines distinct ligand binding and channel specificities. Nature 366:409

    PubMed  Google Scholar 

  41. Endo T, Minami M, Kitamura N, Teramoto Y, Ogawa T, Nemoto M, Hamaue N, Hirafuji M, Yasuda E, Blower PR (1999) Effects of various 5-HT3 receptor antagonists, granisetron, ondansetron, ramosetron and azasetron on serotonin (5-HT) release from the ferret isolated ileum. Res Commun Mol Pathol Pharmacol 104:145

    CAS  PubMed  Google Scholar 

  42. Faulds D, Balfour JA, Chrisp P, Langtry HD (1991) Mitoxantrone: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 41:400

    CAS  PubMed  Google Scholar 

  43. Flaherty JH, Perry HM, Lynchard GS, Morley JE (2000) Polypharmacy and hospitalization among older home care patients. J Gerontol Med Sci 55:554

    Google Scholar 

  44. Fujii Y, Tanaka H (1999) Granisetron reduces post-operative vomiting in children: a dose-ranging study. Eur J Anaesth 16:62

    Article  CAS  Google Scholar 

  45. Fujii Y, Toyooka H, Tanaka H (1996) Effective dose of granisetron for preventing postoperative emesis in children. Can J Anaesth 43:660

    CAS  PubMed  Google Scholar 

  46. Gamse R (1990) Antiemetic action of 5-HT3 receptor antagonists: a review of preclinical and clinical results with ICS 205-930. Cancer Treat Rev 17:301

    CAS  PubMed  Google Scholar 

  47. Gandara DR, Roila F, Warr D, Edelman MJ, Perez EA, Gralla RJ (1998) Consensus proposal for 5-HT3 antagonists in the prevention of acute emesis related to highly emetogenic chemotherapy. Dose, schedule, and route of administration. Support Care Cancer 6:237

    Article  CAS  PubMed  Google Scholar 

  48. Gebauer A, Merger M, Kilbinger H (1993) Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine. Arch Pharmacol 347:137

    CAS  PubMed  Google Scholar 

  49. Goodin S, Cunningham R (2002) 5-HT3-receptor antagonists for the treatment of nausea and vomiting—a re-appraisal of their side-effect profile. Oncologist 7:424

    CAS  PubMed  Google Scholar 

  50. Gralla RJ (1994) Antiemetic treatment for cancer chemotherapy: problems and progress. Support Cancer Care 2:275

    CAS  Google Scholar 

  51. Gralla RJ, Osoba D, Kris MG, Kirkbride P, Hesketh PJ, Chinnery LW, Clark-Snow R, Gill DP, Groshen S, Grunberg S, Koeller JM, Morrow GR, Perez EA, Silber JH, Pfister DG, for the American Society of Clinical Oncology (1999) Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. J Clin Oncol 17:2971

    CAS  PubMed  Google Scholar 

  52. Griffin AM, Butow PN, Coates AS, Childs AM, Ellis PM, Dunn SM, Tattersall MHN (1996) On the receiving end. V: Patient perceptions of the side effects of cancer chemotherapy in 1993. Ann Oncol 7:189

    CAS  PubMed  Google Scholar 

  53. Grote TH, Pineda LF, Figlin RA, Pendergrass KB, Hesketh PJ, Karlan BY, Reeves JA, Potter LL, Benedict CR, Hahne WF (1997) Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Cancer J Sci Am 3:45

    CAS  PubMed  Google Scholar 

  54. Hacking A (1992) Oral granisetron—simple and effective: a preliminary report. The Granisetron Study Group. Eur J Cancer 28A [Suppl 1]:S28

  55. Hesketh PJ (2000) Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Invest 18:163

    CAS  PubMed  Google Scholar 

  56. Hu HZ, Li ZW (1997) Modulation of nicotinic Ach-, GABAA and 5-HT3-receptor functions by external H-7, a protein kinase inhibitor, in rat sensory neurones. Br J Pharmacol 122:1195

    CAS  PubMed  Google Scholar 

  57. Jantunen IT, Muhononen TT, Kataja VV, Flander MK, Teerenhovi L (1993) 5-HT3 receptor antagonists in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy—a randomised study. Eur J Cancer 29A:1669

    CAS  PubMed  Google Scholar 

  58. Kaiser R, Sezer O, Papies A, Bouer S, Schelenz C, Tremblay P, Possinger K, Roots I, Brockmoller J (2002) Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol 20:2805

    Article  CAS  PubMed  Google Scholar 

  59. Kamanabrou D, on behalf of the Granisetron Study Group (1992) Intravenous granisetron—establishing the optimal dose. Eur J Cancer 28A:S6

    PubMed  Google Scholar 

  60. Kytril injection (granisetron hydrochloride) (1999) Prescribing information. SmithKline Beecham Pharmaceuticals, Philadelphia, PA

  61. Leclerc JM, Jacobson SJ, Cohn R, Upward J, Murdoch RD (1993) A double-blind dose-ranging study of IV granisetron in children undergoing highly emetogenic chemotherapy (abstract). Proc Am Soc Clin Oncol 12:437

    Google Scholar 

  62. Lemerle J, Amaral D, Southall DP, Upward J, Murdoch RD (1991) Efficacy and safety of granisetron in the prevention of chemotherapy-induced emesis in paediatric patients. Eur J Cancer 27:1081

    CAS  PubMed  Google Scholar 

  63. Lindley C, Blower P (2000) Oral serotonin type 3-receptor antagonists for prevention of chemotherapy-induced emesis. Am J Health Syst Pharm 57:1685

    CAS  PubMed  Google Scholar 

  64. Mantovani G, Macciò A, Bianchi A, Curreli L, Ghiani M, Proto E, Santona MC (1996) Comparison of granisetron, ondansetron and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial. Cancer 77:941

    Article  CAS  PubMed  Google Scholar 

  65. Mantovani G, Maccio A, Curreli L, Lampis B, Ghiani M, Bianchi A, Contu P (1998) Comparison of oral 5-HT3-receptor antagonists and low-dose oral metoclopramide plus i.m. dexamethasone for the prevention of delayed emesis in head and neck cancer patients receiving high-dose cisplatin. Oncol Rep 5:273

    CAS  PubMed  Google Scholar 

  66. Marr HE, Davey PT, Boyle EA, Blower PR (1994) Further studies of the antiemetic activity of granisetron against whole body X-irradiation or cisplatin-induced emesis in the ferret. Pharmacology 48:238

    Google Scholar 

  67. Martoni A, Piana E, Strocchi E, Angelelli, Guaraldi M, Zamagni C, Camaggi CM, Pannuti F (1998) Comparative crossover trial of two intravenous doses of granisetron (1 mg vs 3 mg) + dexamethasone in the prevention of acute cis-platinum-induced emesis. Anticancer Res 18:2799

    CAS  PubMed  Google Scholar 

  68. Marty M, Kleisbauer J-P, Fournel P, Vergnenegre A, Carles P, Loria-Kanza Y, Simonetta C, de Bruijn KM (1995) Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? Anticancer Drugs 6:15

    Google Scholar 

  69. Mayersohn M (1994) Pharmacokinetics in the elderly. Environ Health Perspect 102 [Suppl 11]:119

  70. Minami M, Endo T, Nemoto M, Hamaue N, Hirafuji M, Monma Y, Yajima T, Yoshioka M, Saito H (1995) How do toxic emetic stimuli cause 5-HT release in the gut and brain? In: Raynolds DJM, Andrews PLR, Davis CJ (eds) Serotonin and the scientific basis of anti-emetic therapy. Oxford Clinical Communications, Oxford, p 68

  71. Miner WD, Sanger GJ (1986) Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. Br J Pharmacol 88:497

    CAS  PubMed  Google Scholar 

  72. Navari RM, Kaplan HG, Gralla RJ, Grunberg SM, Palmer R, Fitts D (1994) Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin. J Clin Oncol 12:2204

    CAS  PubMed  Google Scholar 

  73. Navari R, Gandara D, Hesketh P, Hall S, Mailliard J, Ritter H, Friedman C, Fitts D (1995) Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. J Clin Oncol 13:1242

    CAS  PubMed  Google Scholar 

  74. Navoban (tropisetron hydrochloride) (1997) Approved product information. Novartis Pharmaceuticals Australia, North Ryde, NSW

  75. NCCN (1997) NCCN antiemesis practice guidelines (National Comprehensive Cancer Network, Rockledge, PA). Oncology (Huntingt) 11(11A):57

  76. Newberry NR, Watkins CJ, Sprosen TS, Blackburn TP, Grahame-Smith DG, Leslie RA (1993) BRL 46470 potently antagonizes neural responses activated by 5-HT3 receptors. Neuropharmacology 32:729

    Google Scholar 

  77. Palmer R (1994) Efficacy and safety of granisetron (Kytril) in two special patient populations: children and adults with impaired hepatic function. Semin Oncol 21:22

    CAS  PubMed  Google Scholar 

  78. Parker RM, Bentley KR, Barnes NM (1996) Allosteric modulation of 5-HT3 receptors: focus on alcohols and anaesthetic agents. Trends Pharmacol Sci. 17:95

    Google Scholar 

  79. Perez EA (1991) Review of the preclinical pharmacology and comparative efficacy of 5-hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis. J Clin Oncol 13:1036

    Google Scholar 

  80. Perez EA, Hesketh P, Sandbach J, Reeves J, Chawla S, Markman M, Hainsworth J, Bushnell W, Friedman C (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

    CAS  PubMed  Google Scholar 

  81. Riviere A, on behalf of The Granisetron Study Group (1994) Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. Br J Cancer 69:967

    CAS  PubMed  Google Scholar 

  82. Roila F, Tonato M, Basurto C, Bella M, Passalacqua R, Morsia D, DiCostanzo F, Donati D, Ballatori E, Tognoni G, Franzosi MG, Favero AD (1987) Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research. J Clin Oncol 5:141

    CAS  PubMed  Google Scholar 

  83. Rowinsky EK, Donehower RC (1995) Paclitaxel (Taxol). N Engl J Med 332:1004

    CAS  PubMed  Google Scholar 

  84. Sanchez LA, Holdsworth M, Bartel SB (2000) Stratified administration of serotonin 5-HT3 receptor antagonists (setrons) for chemotherapy-induced emesis. Pharmacoeconomics 18:533

    CAS  PubMed  Google Scholar 

  85. Sanwald P, David M, Dow J (1996) Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Drug Metab Dispos 24:602

    Google Scholar 

  86. Seynaeve C, Schuller J, Buser K, Porteder H, Van Belle S, Sevelda P, Christmann D, Schmidt M, Kitchener H, Paes D, de Mulder PHM (1992) Comparison of the anti-emetic efficacy of different doses of ondansetron, given as either a continuous infusion or a single intravenous dose, in acute cisplatin-induced emesis. A multicentre, double-blind, randomised, parallel group study. Br J Cancer 66:192

    CAS  PubMed  Google Scholar 

  87. Sigsgaard T, Herrstedt J, Anderson LJ, Havsteen H, Langer SW, Kjaerbol A-G, Lund H, Kjaer M, Dombernowsky P (1999) Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy. Br J Cancer 80:412

    Article  CAS  PubMed  Google Scholar 

  88. Smith IE (1993) A dose-finding study of granisetron, a novel antiemetic, in patients receiving cytostatic chemotherapy. J Cancer Res Clin Oncol 119:350

    CAS  PubMed  Google Scholar 

  89. Soukop M (1994) A dose-finding study of granisetron, a novel antiemetic, in patients receiving high-dose cisplatin. Support Care Cancer 2:177

    CAS  PubMed  Google Scholar 

  90. Terrey J-P, Aapro MS (1996) The activity of granisetron in patients who had previously failed ondansetron antiemetic therapy. Eur J Clin Res 8:281

    Google Scholar 

  91. Tsavaris N, Kosmas M, Vadiaka CH, Vadiaka M, Kontos A, Katsorida M, Dimitrakopoulos A, Zerai A, Koufos CH (2001) Efficacy of ondansetron treatment for acute emesis with different dosing schedules 8 vs 32 mg. A randomized study. J Exp Clin Cancer Res 20:29

    CAS  PubMed  Google Scholar 

  92. Tsuchida Y, Hayashi Y, Asami K, Yamamoto K, Yokoyama J, Mugishima H, Honna T, Mimaya J, Hara F, Sawada T, Matsumura T, Suita S, Sugimoto T, Kaneko M (1999) Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study. Int J Oncol 14:673

    CAS  PubMed  Google Scholar 

  93. Tuladhar BR, Womack MD, Naylor RJ (2000) Pharmacological characterization of the 5-HT receptor-mediated contraction in the mouse isolated ileum. Br J Pharmacol 131:1716

    CAS  PubMed  Google Scholar 

  94. Upward JW, Arnold BDC, Link C, Pierce DM, Allen A, Tasker TCG (1990) The clinical pharmacology of granisetron (BRL 43694), a novel specific 5-HT3 antagonist. Eur J Cancer 26 [Suppl 1]:S12

  95. van Belle SJ-P, Stamatakis L, Bleiberg H, Cocquyt VFJ, Michel J, de Bruijn KM (1994) Dose-finding study of tropisetron in cisplatin-induced nausea and vomiting. Ann Oncol 5:82

    Google Scholar 

  96. van Hooft JA, van der Haar E, Vijverberg HP (1997) Allosteric potentiation of the 5-HT3 receptor-mediated ion current in N1E-115 neuroblastoma cells by 5-hydroxyindole and analogues. Neuropharmacology 36:649

    Article  PubMed  Google Scholar 

  97. van Wijngaarden I, Tulp MT, Soudijn W (1990) The concept of selectivity in 5-HT receptor research. Eur J Pharmacol 138:301

    Google Scholar 

  98. Wei JY (1995) Cardiovascular comorbidity in the older cancer patient. Semin Oncol 22:9

    CAS  Google Scholar 

  99. Yancik R (1997) Cancer burden in the aged. Cancer 80:1273

    Article  CAS  PubMed  Google Scholar 

  100. Zofran injection (ondansetron hydrochloride) (1996) Prescribing information. Glaxo Wellcome, Research Triangle Park, NC

Download references

Acknowledgements

Support during the preparation of this report was provided by Hoffman-La Roche.

Author information

Affiliations

  1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, 0610293, Japan

    Masaru Minami

Authors
  1. Masaru Minami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaru Minami.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Minami, M. Granisetron: is there a dose–response effect on nausea and vomiting?. Cancer Chemother Pharmacol 52, 89–98 (2003). https://doi.org/10.1007/s00280-003-0652-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-003-0652-6

Keywords

  • Dose-response
  • Granisetron
  • 5-HT3 receptor antagonist
  • Antiemetic
  • Supportive care