Skip to main content

First-Generation 5-HT3 Receptor Antagonists

  • Chapter
  • First Online:
Management of Chemotherapy-Induced Nausea and Vomiting

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect of cancer therapy and can lead to poor compliance with therapy, treatment delays, dehydration, hospitalization, and a marked decrement in patient quality of life. With appropriate CINV control, safe outpatient administration of chemotherapy can be accomplished with no change in patients’ pre-therapy quality of life. Over the last 30 years, developments have improved in the control of CINV, including the advent of 5-hydroxytryptamine-3 (5HT-3) receptor antagonists which are an integral ingredient in regimens used today. With the variety of chemotherapy regimens today and the ongoing development of new combinations in addition to targeted therapy, there have been corresponding dynamic goals for control of not only CINV in general but in differentiating control of nausea over and above that of vomiting. In fact, current antiemetic therapy conceptually fulfills the true definition of “targeted therapy” as there is significant understanding of pathways involved in emesis as well as specific targeted antagonists to these pathways. This chapter will focus on the 5HT-3 pathway and the specific receptor antagonists to this pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Markman M (2002) Progress in preventing chemotherapy-induced nausea and vomiting. Cleve Clin J Med 69:609–610, 612, 615–7

    Article  PubMed  Google Scholar 

  2. Roila F, Herrstedt J, Aapro M et al (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(Suppl 5):v232–v243

    Article  PubMed  Google Scholar 

  3. Kris MG, Gralla RJ, Clark RA et al (1985) Incidence, course, and severity of delayed nausea and vomiting following the administration of high-dose cisplatin. J Clin Oncol 3:1379–1384

    CAS  PubMed  Google Scholar 

  4. Thumas L (1891) Ueber das Brechcentrum und über die Wirkung einiger pharmakologischer Mittel auf dasselbe. Virchows Arch 123:44–69

    Article  Google Scholar 

  5. Wang SC, Borison HL (1950) The vomiting center; a critical experimental analysis. Arch Neurol Psychiatry 63:928–941

    Article  CAS  PubMed  Google Scholar 

  6. Koga T, Fukuda H (1992) Neurons in the nucleus of the solitary tract mediating inputs from emetic vagal afferents and the area postrema to the pattern generator for the emetic act in dogs. Neurosci Res 14:166–179

    Article  CAS  PubMed  Google Scholar 

  7. Andrews PL, Davis CJ, Bingham S et al (1990) The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity. Can J Physiol Pharmacol 68:325–345

    Article  CAS  PubMed  Google Scholar 

  8. Leslie RA, Shah Y, Thejomayen M et al (1990) The neuropharmacology of emesis: the role of receptors in neuromodulation of nausea and vomiting. Can J Physiol Pharmacol 68:279–288

    Article  CAS  PubMed  Google Scholar 

  9. Kris MG, Gralla RJ, Tyson LB et al (1985) Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine. Results of consecutive trials in 255 patients. Cancer 55:527–534

    Article  CAS  PubMed  Google Scholar 

  10. Butler A, Hill JM, Ireland SJ et al (1988) Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors. Br J Pharmacol 94:397–412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Fozard JR, Mobarok Ali AT, Newgrosh G (1979) Blockade of serotonin receptors on autonomic neurones by (-)-cocaine and some related compounds. Eur J Pharmacol 59:195–210

    Article  CAS  PubMed  Google Scholar 

  12. Buchheit KH, Costall B, Engel G et al (1985) 5-Hydroxytryptamine receptor antagonism by metoclopramide and ICS 205–930 in the guinea-pig leads to enhancement of contractions of stomach muscle strips induced by electrical field stimulation and facilitation of gastric emptying in-vivo. J Pharm Pharmacol 37:664–667

    Article  CAS  PubMed  Google Scholar 

  13. Yan D, Schulte MK, Bloom KE et al (1999) Structural features of the ligand-binding domain of the serotonin 5-HT3 receptor. J Biol Chem 274:5537–5541

    Google Scholar 

  14. National Center for Biotechnology Information. PubChem Compound Database; CID = 4595. http://pubchem.ncbi.nlm.nih.gov/compound/ondansetron#section=Top. Accessed 11 Feb 2015

  15. National Center for Biotechnology Information (2015) PubChem Compound Database; CID = 3148. http://pubchem.ncbi.nlm.nih.gov/compound/3148. Accessed 11 Feb 2015

  16. National Center for Biotechnology Information (2015) PubChem Compound Database; CID = 656665. http://pubchem.ncbi.nlm.nih.gov/compound/tropisetron. Accessed 11 Feb 2015

  17. National Center for Biotechnology Information (2015) PubChem Compound Database; CID = 5284566. http://pubchem.ncbi.nlm.nih.gov/compound/granisetron. Accessed 11 Feb 2015

  18. Blackwell CP, Harding SM (1989) The clinical pharmacology of ondansetron. Eur J Cancer Clin Oncol 25(Suppl 1):S21–S24, discussion S25–7

    PubMed  Google Scholar 

  19. Pritchard JF, Bryson JC, Kernodle AE et al (1992) Age and gender effects on ondansetron pharmacokinetics: evaluation of healthy aged volunteers. Clin Pharmacol Ther 51:51–55

    Article  CAS  PubMed  Google Scholar 

  20. Zuo P, Haberer LJ, Fang L et al (2014) Integration of modeling and simulation to support changes to ondansetron dosing following a randomized, double-blind, placebo-, and active-controlled thorough QT study. J Clin Pharmacol 54:1221–1229

    Article  CAS  PubMed  Google Scholar 

  21. Boxenbaum H, Gillespie T, Heck K et al (1992) Human dolasetron pharmacokinetics: I. Disposition following single-dose intravenous administration to normal male subjects. Biopharm Drug Dispos 13:693–701

    Article  CAS  PubMed  Google Scholar 

  22. Kees F, Farber L, Bucher M et al (2001) Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers. Br J Clin Pharmacol 52:705–707

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Kim MK, Cho JY, Lim HS et al (2003) Effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects. Eur J Clin Pharmacol 59:111–116

    CAS  PubMed  Google Scholar 

  24. Carmichael J, Cantwell BM, Edwards CM et al (1989) A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response. Cancer Chemother Pharmacol 24:45–49

    CAS  PubMed  Google Scholar 

  25. Clark RD, Miller AB, Berger J et al (1993) 2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists. J Med Chem 36:2645–2657

    Article  CAS  PubMed  Google Scholar 

  26. National Center for Biotechnology Information (2015) PubChem Compound Database; CID = 6337614. http://pubchem.ncbi.nlm.nih.gov/compound/Palonosetron. Accessed 11 Feb 2015

  27. Yavas C, Dogan U, Yavas G et al (2012) Acute effect of palonosetron on electrocardiographic parameters in cancer patients: a prospective study. Support Care Cancer 20:2343–2347

    Article  CAS  PubMed  Google Scholar 

  28. Yang LP, Scott LJ (2009) Palonosetron: in the prevention of nausea and vomiting. Drugs 69:2257–2278

    Article  CAS  PubMed  Google Scholar 

  29. Cubeddu LX, Hoffmann IS, Fuenmayor NT et al (1990) Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med 322:810–816

    Article  CAS  PubMed  Google Scholar 

  30. Cupissol DR, Serrou B, Caubel M (1990) The efficacy of granisetron as a prophylactic anti-emetic and intervention agent in high-dose cisplatin-induced emesis. Eur J Cancer 26(Suppl 1):S23–S27

    PubMed  Google Scholar 

  31. Cubeddu LX, Hoffman IS, Fuenmayor NT et al (1990) Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens. J Clin Oncol 8:1721–1727

    CAS  PubMed  Google Scholar 

  32. Ikeda M, Taguchi T, Ota K et al (1992) Evaluation of SN-307 (ondansetron), given intravenously in the treatment of nausea and vomiting caused by anticancer drugs including cisplatin – a placebo-controlled, double-blind comparative study. Gan To Kagaku Ryoho 19:2071–2084

    CAS  PubMed  Google Scholar 

  33. Kondo M, Furue H, Taguchi T et al (1995) Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drug; a placebo-controlled, multicenter, double-blind comparative study. Gan To Kagaku Ryoho 22:1223–1234

    CAS  PubMed  Google Scholar 

  34. McVie JG, de Bruijn KM (1992) Methodology of antiemetic trials. Drugs 43(Suppl 3):1–5

    Article  PubMed  Google Scholar 

  35. Kris MG, Cubeddu LX, Gralla RJ et al (1996) Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin. Cancer 78:2193–2198

    Article  CAS  PubMed  Google Scholar 

  36. Grunberg SM, Lane M, Lester EP et al (1993) Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis. Cancer Chemother Pharmacol 32:268–272

    Article  CAS  PubMed  Google Scholar 

  37. Riviere A (1994) Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group. Br J Cancer 69:967–971

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Soukop M (1994) A dose-finding study of granisetron, a novel antiemetic, in patients receiving high-dose cisplatin. Granisetron Study Group. Support Care Cancer 2:177–183

    Article  CAS  PubMed  Google Scholar 

  39. Van Belle SJ, Stamatakis L, Bleiberg H et al (1994) Dose-finding study of tropisetron in cisplatin-induced nausea and vomiting. Ann Oncol 5:821–825

    PubMed  Google Scholar 

  40. Kris MG, Grunberg SM, Gralla RJ et al (1994) Dose-ranging evaluation of the serotonin antagonist dolasetron mesylate in patients receiving high-dose cisplatin. J Clin Oncol 12:1045–1049

    CAS  PubMed  Google Scholar 

  41. Hainsworth J, Harvey W, Pendergrass K et al (1991) A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy. J Clin Oncol 9:721–728

    CAS  PubMed  Google Scholar 

  42. De Mulder PH, Seynaeve C, Vermorken JB et al (1990) Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study. Ann Intern Med 113:834–840

    Article  PubMed  Google Scholar 

  43. Marty M, Pouillart P, Scholl S et al (1990) Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. N Engl J Med 322:816–821

    Article  CAS  PubMed  Google Scholar 

  44. Warr D, Willan A, Fine S et al (1991) Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis. J Natl Cancer Inst 83:1169–1173

    Article  CAS  PubMed  Google Scholar 

  45. Marty M (1992) A comparison of granisetron as a single agent with conventional combination antiemetic therapies in the treatment of cytostatic-induced emesis. The Granisetron Study Group. Eur J Cancer 28A(Suppl 1):S12–S16

    Article  PubMed  Google Scholar 

  46. Warr D, Wilan A, Venner P et al (1992) A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis. An NCI Canada Clinical Trials Group Phase III Trial. Eur J Cancer 29A:33–36

    CAS  PubMed  Google Scholar 

  47. Jantunen IT, Kataja VV, Muhonen TT (1997) An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting. Eur J Cancer 33:66–74

    Article  CAS  PubMed  Google Scholar 

  48. Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. Italian Group for Antiemetic Research (1998) J Clin Oncol 16:2937–2942

    Google Scholar 

  49. Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide (2004) J Clin Oncol 22:725–729

    Google Scholar 

  50. Ruff P, Paska W, Goedhals L et al (1994) Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. The Ondansetron and Granisetron Emesis Study Group. Oncology 51:113–118

    Article  CAS  PubMed  Google Scholar 

  51. Noble A, Bremer K, Goedhals L et al (1994) A double-blind, randomised, crossover comparison of granisetron and ondansetron in 5-day fractionated chemotherapy: assessment of efficacy, safety and patient preference. The Granisetron Study Group. Eur J Cancer 30A:1083–1088

    Article  CAS  PubMed  Google Scholar 

  52. Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis. Italian Group of Antiemetic Research (1995) Ann Oncol 6:805–810

    Google Scholar 

  53. Bonneterre J, Hecquet B (1995) Granisetron (IV) compared with ondansetron (IV plus oral) in the prevention of nausea and vomiting induced by moderately-emetogenic chemotherapy. A cross-over study. Bull Cancer 82:1038–1043

    CAS  PubMed  Google Scholar 

  54. Navari R, Gandara D, Hesketh P et al (1995) Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol 13:1242–1248

    CAS  PubMed  Google Scholar 

  55. Stewart A, McQuade B, Cronje JD et al (1995) Ondansetron compared with granisetron in the prophylaxis of cyclophosphamide-induced emesis in out-patients: a multicentre, double-blind, double-dummy, randomised, parallel-group study. Emesis Study Group for Ondansetron and Granisetron in Breast Cancer Patients. Oncology 52:202–210

    Article  CAS  PubMed  Google Scholar 

  56. Martoni A, Angelelli B, Guaraldi M et al (1996) An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens. Eur J Cancer 32A:82–85

    Article  CAS  PubMed  Google Scholar 

  57. Chua DT, Sham JS, Kwong DL et al (2000) Comparative efficacy of three 5-HT3 antagonists (granisetron, ondansetron, and tropisetron) plus dexamethasone for the prevention of cisplatin-induced acute emesis: a randomized crossover study. Am J Clin Oncol 23:185–191

    Article  CAS  PubMed  Google Scholar 

  58. Oge A, Alkis N, Oge O et al (2000) Comparison of granisetron, ondansetron and tropisetron for control of vomiting and nausea induced by cisplatin. J Chemother 12:105–108

    CAS  PubMed  Google Scholar 

  59. Audhuy B, Cappelaere P, Martin M et al (1996) A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesylate and granisetron in patients receiving high dose cisplatin chemotherapy. Eur J Cancer 32A:807–813

    CAS  PubMed  Google Scholar 

  60. Fauser AA, Duclos B, Chemaissani A et al (1996) Therapeutic equivalence of single oral doses of dolasetron mesylate and multiple doses of ondansetron for the prevention of emesis after moderately emetogenic chemotherapy. European Dolasetron Comparative Study Group. Eur J Cancer 32A:1523–1529

    Article  CAS  PubMed  Google Scholar 

  61. Lofters WS, Pater JL, Zee B et al (1997) Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy. J Clin Oncol 15:2966–2973

    CAS  PubMed  Google Scholar 

  62. Hesketh PJ (2000) Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Investig 18:163–173

    Article  CAS  Google Scholar 

  63. Jordan K, Hinke A, Grothey A et al (2007) A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis. Support Care Cancer 15:1023–1033

    Article  CAS  PubMed  Google Scholar 

  64. Clarke SE, Austin NE, Bloomer JC et al (1994) Metabolism and disposition of 14C-granisetron in rat, dog and man after intravenous and oral dosing. Xenobiotica 24:1119–1131

    Article  CAS  PubMed  Google Scholar 

  65. Dimmitt DC, Choo YS, Martin LA et al (1999) Intravenous pharmacokinetics and absolute oral bioavailability of dolasetron in healthy volunteers: part 1. Biopharm Drug Dispos 20:29–39

    Article  CAS  PubMed  Google Scholar 

  66. Needles B, Miranda E, Garcia Rodriguez FM et al (1999) A multicenter, double-blind, randomized comparison of oral ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with highly emetogenic chemotherapy. S3AA3012 Study Group. Support Care Cancer 7:347–353

    Article  CAS  PubMed  Google Scholar 

  67. Rubenstein EB, Gralla RJ, Hainsworth JD et al (1997) Randomized, double blind, dose-response trial across four oral doses of dolasetron for the prevention of acute emesis after moderately emetogenic chemotherapy. Oral Dolasetron Dose-Response Study Group. Cancer 79:1216–1224

    Article  CAS  PubMed  Google Scholar 

  68. Bleiberg HH, Spielmann M, Falkson G et al (1995) Antiemetic treatment with oral granisetron in patients receiving moderately emetogenic chemotherapy: a dose-ranging study. Clin Ther 17:38–51

    Article  CAS  PubMed  Google Scholar 

  69. Krzakowski M, Graham E, Goedhals L et al (1998) A multicenter, double-blind comparison of i.v. and oral administration of ondansetron plus dexamethasone for acute cisplatin-induced emesis. Ondansetron Acute Emesis Study Group. Anticancer Drugs 9:593–598

    Article  CAS  PubMed  Google Scholar 

  70. Gralla RJ, Navari RM, Hesketh PJ et al (1998) Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy. J Clin Oncol 16:1568–1573

    CAS  PubMed  Google Scholar 

  71. 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 16:754–760

    CAS  PubMed  Google Scholar 

  72. Spector JI, Lester EP, Chevlen EM et al (1998) A comparison of oral ondansetron and intravenous granisetron for the prevention of nausea and emesis associated with cisplatin-based chemotherapy. Oncologist 3:432–438

    CAS  PubMed  Google Scholar 

  73. Navari RM, Madajewicz S, Anderson N et al (1995) Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo. J Clin Oncol 13:2408–2416

    CAS  PubMed  Google Scholar 

  74. Olver I, Paska W, Depierre A et al (1996) A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron Delayed Emesis Study Group. Ann Oncol 7:945–952

    Article  CAS  PubMed  Google Scholar 

  75. Geling O, Eichler HG (2005) Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol 23:1289–1294

    Article  CAS  PubMed  Google Scholar 

  76. Lanciano R, Sherman DM, Michalski J et al (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 19:763–772

    Article  CAS  PubMed  Google Scholar 

  77. Spitzer TR, Friedman CJ, Bushnell W et al (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 26:203–210

    Article  CAS  PubMed  Google Scholar 

  78. Rojas C, Stathis M, Thomas AG et al (2008) Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg 107:469–478

    Article  CAS  PubMed  Google Scholar 

  79. Rojas C, Thomas AG, Alt J et al (2010) Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol 626:193–199

    Article  CAS  PubMed  Google Scholar 

  80. Gralla R, Lichinitser M, Van Der Vegt S et al (2003) Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 14:1570–1577

    Article  CAS  PubMed  Google Scholar 

  81. Eisenberg P, Figueroa-Vadillo J, Zamora R et al (2003) Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 98:2473–2482

    Article  CAS  PubMed  Google Scholar 

  82. Aapro MS, Grunberg SM, Manikhas GM et al (2006) A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 17:1441–1449

    Article  CAS  PubMed  Google Scholar 

  83. Saito M, Aogi K, Sekine I et al (2009) Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 10:115–124

    Article  CAS  PubMed  Google Scholar 

  84. Boccia R, Grunberg S, Franco-Gonzales E et al (2013) Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial. Support Care Cancer 21:1453–1460

    Article  PubMed Central  PubMed  Google Scholar 

  85. Gurpide A, Sadaba B, Martin-Algarra S et al (2007) Randomized crossover pharmacokinetic evaluation of subcutaneous versus intravenous granisetron in cancer patients treated with platinum-based chemotherapy. Oncologist 12:1151–1155

    Article  CAS  PubMed  Google Scholar 

  86. Roila F, Del Favero A (1995) Ondansetron clinical pharmacokinetics. Clin Pharmacokinet 29:95–109

    Article  CAS  PubMed  Google Scholar 

  87. Howell J, Smeets J, Drenth HJ et al (2009) Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting. J Oncol Pharm Pract 15:223–231

    Article  CAS  PubMed  Google Scholar 

  88. Boccia RV, Gordan LN, Clark G et al (2011) Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer 19:1609–1617

    Article  PubMed Central  PubMed  Google Scholar 

  89. Heller J, Barr J (2005) Biochronomer technology. Expert Opin Drug Deliv 2:169–183

    Article  CAS  PubMed  Google Scholar 

  90. Raftopoulos H, Cooper W, O’Boyle E et al (2015) Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial. Support Care Cancer 23:723–732

    Article  PubMed Central  PubMed  Google Scholar 

  91. Hesketh PJ, Kris MG, Grunberg SM et al (1997) Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 15:103–109

    CAS  PubMed  Google Scholar 

  92. Basch E, Prestrud AA, Hesketh PJ et al (2011) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29:4189–4198

    Article  PubMed  Google Scholar 

  93. Raftopoulos H, Boccia RV, Cooper W et al (2014) A prospective, randomized, double-blind phase 3 trial of extended-release granisetron (APF530) versus palonosetron (PALO) for preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately (MEC) or highly (HEC) emetogenic chemotherapy: does a reanalysis using newer ASCO emetogenicity criteria affect study conclusions? ASCO Meet Abstr 32:9648

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harry Raftopoulos MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Chen, R., Deng, K., Raftopoulos, H. (2016). First-Generation 5-HT3 Receptor Antagonists. In: Navari, R. (eds) Management of Chemotherapy-Induced Nausea and Vomiting. Adis, Cham. https://doi.org/10.1007/978-3-319-27016-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-27016-6_3

  • Published:

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-27014-2

  • Online ISBN: 978-3-319-27016-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics