Mechanisms and Treatment of Cytotoxic-Induced Nausea and Vomiting

  • A. L. Harris
  • B. M. J. Cantwell
Part of the Advances in Applied Neurological Sciences book series (NEUROLOGICAL, volume 3)


The most important subjective side-effects of cancer chemotherapy are nausea and vomiting. It is not known how such a wide variety of cytotoxic agents with different structures, modes of action and lipid solubility produce nausea and vomiting. The ability to recognise poisonous substances may have been of great evolutionary value but is a disadvantage in managing patients with cancer.


Area Postrema Proc ASCO Antiemetic Efficacy Free Nerve Ending Chemoreceptor Trigger Zone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Aapro M, Menoud M, Peytramann R, Alberto P (1984) Antiemetic combination dexamethasone, droperidol, diphenhydramine for DTIC or cisplatin-induced nausea and vomiting. Proc ASCO 3: C - 393Google Scholar
  2. Alayi JB, Tom S, Glick JH (1984) High dose oral metoclopramide: an effective antiemetic agent. Proc ASCO 3: C - 424Google Scholar
  3. Allan S, Combleet M, Warrington P, Leonard R, Smythe J (1984) Trial of dexamethasone and high dose metoclopramide vs placebo and high dose metoclopramide in cis-platinum induced emesis. Proc ASCO 3: C - 345Google Scholar
  4. Anthony LB, Krozely MG, Woodward NJ, Hainsworth JD, Harde KR, Brenner DE, Graco FA, Burish TG (1984) Antiemetic effect of oral vs intravenous metoclopramide in patients receiving cisplatin: a randomised double-blind study. Proc ASCO 3: C - 404Google Scholar
  5. Arnold DJ, Ribiero V, Bulkin W (1980) Metoclopramide vs prochlorperazine in the prevention of vomiting from diammine dichloroplatinum. Proc ASCO 21: 344Google Scholar
  6. Belt RJ, Rhodes J, Taylor S (1981) Antiemetic therapy for patients receiving cisdiamminedichloroplatinum (11): a randomised double-blind study comparing metoclopramide and prochlorperazine. In: Poster DS, Penta JS, Bruno S (eds) Treatment of cancer chemotherapy-induced nausea and vomiting. Masson, New York, pp 153–158Google Scholar
  7. Bowcock SJ, Stockdale AD, Bolton JAR, Kang AA, Retsas S (1984) Antiemetic prophylaxis with high dose metoclopramide or lorazepam in vomiting induced by chemotherapy. Br Med J 288: 1879CrossRefGoogle Scholar
  8. Borison HL, McCarthy LE (1983) Neuropharmacologic mechanisms of emesis In Laszlo J (ed) Antiemetics and cancer chemotherapy. Williams and Wilkins, Baltimore, pp 6–29Google Scholar
  9. Borison HL, Wang SC (1953) Physiology and pharmacology of vomiting. Pharmacol Rev 5: 192–230Google Scholar
  10. Borison HL, Brand D, Orchard RH (1958) Emetic action of nitrogen mustard in dogs and cats. Am J Physiol 192: 410–416PubMedGoogle Scholar
  11. Broadwell RD, Brightman MW (1976) Entry of peroxidase into neurons of the central and peripheral nervous system from extracerebral and cerebral blood. J Comp Neurol 166: 257–284PubMedCrossRefGoogle Scholar
  12. Bui NB, Marit G, Hoerni B (1982) High dose metoclopramide in cancer chemotherapy-induced nausea and vomiting. Cancer Treat Rep 66: 2107–2108PubMedGoogle Scholar
  13. Carr B, Pulone B, Bertrand M, Browning S, Doroshow J, Klein L, Presant C, Change FF (1982) A double-blind comparison of metoclopramide and prochlorperazine for cisplatinum-induced emesis. Proc ASCO 1: 66Google Scholar
  14. Carr BI, Leong L, Cecchi G, Braly P, Staples R, Blayney D, Goldberg D, Maryslin K, Bertrand M, Doroshow J (1984) Safety and efficacy of higher than conventional doses of prochlorperazine for chemotherapy-associated emesis. Proc ASCO 3: G394Google Scholar
  15. Cassileth PA, Lusk EJ, Toni S, DiNubile N, Gerson SL (1983) Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. Arch Intern Med 143: 1347–1349PubMedCrossRefGoogle Scholar
  16. Chang SE, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, Simon RM, Rosenberg SA (1979) Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high dose methotrexate. Ann Intern Med 91: 819–824PubMedGoogle Scholar
  17. Citron ML, Johnston-Early A, Boyer MW, Krasnow SH, Priebat DA, Cohen MH (1984) Droperidol: optimal dose and time of initiation. Proc ASCO 3: C - 415Google Scholar
  18. Cognetti F, Pinnaro P, Carlini P, Conti EM, Cortese M, Pollera CF (1984) Randomised open cross-over trial between metoclopramide and dexamethasone for the prevention of cisplatininduced nausea and vomiting. Eur J Cancer Clin Oncol 20: 183–187PubMedCrossRefGoogle Scholar
  19. Cotanch PH (1983) Relaxation techniques as antiemetic therapy. In: Laszlo J (ed) Antiemetics and cancer chemotherapy. Williams and Wilkins, Baltimore, pp 164–175Google Scholar
  20. Costello DJ, Borison HL (1977) Naloxone antagonises narcotic self-blockade of emesis in the cat. J Pharmacol Exp Ther 203: 222–230PubMedGoogle Scholar
  21. Deppe G, Smith P, Wall D, Malviya VK (1984) A comparison of the antiemetic effects of low dose and high dose metoclopramide in gynecologic cancer patients receiving cisplatin. Proc ASCO 3: C - 365Google Scholar
  22. D’Olimpio JT, Camacho FJ, Chandra P, Lesser M, Maldonado M, Wollner D, Wiernik PH (1984) Antiemetic treatment of patients receiving cisplatin-based chemotherapy with high dose dexamethasone v placebo. Proc ASCO 3: C - 371Google Scholar
  23. D’Souza DP, Reyntjens A, Thornes RD (1980) Domperidone in the prevention of nausea and vomiting induced by antineoplastic agents: a three-fold evaluation. Curr Ther Res 27: 384–390Google Scholar
  24. Edge S, Fundhouser W, Berman A, Seipp C, Tanner A, Wesley R, Rosenburg S, Chang A (1984) Randomised evaluation of high dose oral and intravenous metoclopramide in adriamycin/ cytoxan induced emesis. Proc ASCO 3: C - 378Google Scholar
  25. Ettinger DS, Sheidler V, Markman M, Quaskey SA, Mellits ED (1984) Antiemetic efficacy of dexamethasone: randomised double-blind crossover study with prochlorperazine. Proc ASCO 3: C - 350Google Scholar
  26. Fetting JH, Grochow LB, Folstein MF, Ettinger DS, Colvin M (1982) The course of nausea and vomiting after high dose cyclophosphamide. Cancer Treat Rep 66: 1487–1493PubMedGoogle Scholar
  27. Friedlander M, Kearsley JH, Tattersall MHN (1981) Oral lorazepam to improve tolerance of cytotoxic therapy. Lancet 1: 1316–1317PubMedCrossRefGoogle Scholar
  28. Frytak S, Moertel CG (1981) Management of nausea and vomiting in the cancer patient. JAMA 245: 393–396PubMedCrossRefGoogle Scholar
  29. Frytak S, Moertel CG, O’Fallon JR (1979) Delta-9-tetrahydrocanna-binol as an antiemetic for patients receiving cancer chemotherapy. Ann Intern Med 91: 825–830PubMedGoogle Scholar
  30. Gagen M, Gochnour D, Young D, Gaginella T, Neidhart J (1984) Dexamethasone and lorazepam vs metoclopramide for prevention of chemotherapy-induced vomiting. Proc ASCO 3: C396Google Scholar
  31. Gercovich FG, Nahmod VE, Pirole CJ, Morgenfeld EL, Rivarola EJ (1984) A double-blind randomised cross-over study comparing domperidone to metoclopramide as an antiemetic prevention in cancer chemotherapy. Proc ASCO 3: C - 344Google Scholar
  32. Gralla RJ, Hri LM, Pisko SE, Squillante AE, Kelsen DP, Braun DW Jr, Bordin LA, Braun TJ, Young CW (1981) Antiemetic efficacy of high-dose metoclopramide. Randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. N Engl J Med 305: 905–909PubMedCrossRefGoogle Scholar
  33. Gralla RJ, Tyson LB, Clark RA, Bordin LA, Kelsen DP, Kalman LB (1982) Antiemetic trials with high dose metoclopramide: superiority over THC and preservation of efficacy in subsequent chemotherapy courses. Proc ASCO 1: 58Google Scholar
  34. Guidotti A, Baraldi M, Costa E (1979) 1–4-Benzodiazepines and gamma-aminobutyric acid: pharmacological and biochemical correlates. Pharmacology 19:267–277PubMedCrossRefGoogle Scholar
  35. Harris AL (1982) Cytotoxi99-therapy-induced vomiting is mediated via enkephalin pathways. Lancet 1: 714–716PubMedCrossRefGoogle Scholar
  36. Hamers J (1978) Cytostatic therapy induced vomiting inhibited by domperidone: a double-blind cross-over study. Biomedicine 29: 242–244PubMedGoogle Scholar
  37. Herz A, Hoolt V, Gramsch C, Seizinger BR (1982) In: Costa E, Trabbuch M (eds) Regulatory peptides from molecular biology to function. Raven, New York, pp 51–59Google Scholar
  38. Herman TS, Einhorn LH, Jones SE, Hagy C, Chester AB, Dean JC, Fumas B, Williams SD, Leigh SA, Don RT, Moon TE (1979) Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. N Engl J Med 300: 1295–1297PubMedCrossRefGoogle Scholar
  39. Huys J (1978) Cytostati99-associated vomiting effectively inhibited by domperidone. Cancer Chemother Pharmacol 1: 215–218PubMedCrossRefGoogle Scholar
  40. Jacobs AJ, Deppe G, Cohen CJ (1980) A comparison of the antiemetic effects of droperidol and prochlorperazine in chemotherapy with cis-platinum. Gynecol Oncol 10: 55–57PubMedCrossRefGoogle Scholar
  41. Jardine I, Ferselav C, Appler M et al. (1978) Quantitation by gas chromatography - chemical ionisation, mass spectrometry of cyclophosphamide, phosphoramide mustard and nornitrogen mustard in the plasma and urine of patients receiving cyclophosphamide therapy. Cancer Res 38: 408PubMedGoogle Scholar
  42. Kelley SL, Braun TJ, Rempel P, Meyer TJ, Pearlman NW (1984) Phase 1 trial of droperidol as an antiemetic in cisplatin-induced emesis. Proc ASCO 3: C - 382Google Scholar
  43. Kessler JF, Plezia PM, Alberts DS, Aapro MS, Surwitt EA, Graham V, Chase J (1984) Five frug antiemetic combination for prevention of chemotherapy related nausea and vomiting. Proc ASCO 3: C - 406Google Scholar
  44. Lane R, McGee R, Riukin S (1982) Antiemetic combinations for control of platinum induced emesis. Proc ASCO 1: 65Google Scholar
  45. Levitt M, Wilson A, Burman D, Fairman C, Kemel S, Krepart G, Schipper H, Weinerman B, Weinerman R (1981) Dose vs response of tetrahydrocannabinol vs prochlorperazine as chemotherapy antiemetics. Proc ASCO 22: 422Google Scholar
  46. Long A, Mioduszewski J, Natale R (1982) A randomised double-blind crossover comparison of the antiemetic activity of levonantrodol and prochlorperazine. Proc ASCO 1: 57Google Scholar
  47. McCabe M, Smith FP, Goldberg D, MacDonald J, Woolley PV, Warren R, Brodeur R, Schein PS (1981) Comparative trial of oral 9-tetrahydrocannabinol and prochlorperazine for cancer chemotherapy-related nausea and vomiting. Proc ASCO 22: 416Google Scholar
  48. McDermed JE, Waugh WJ, Strum SB (1984) A preliminary pharmacokinetic evaluation of high dose metoclopramide in patients receiving cisplatinum chemotherapy. Proc ASCO 3: C - 409Google Scholar
  49. Meyer BR, Lewin M, Drayer DE, Pasmartier M, Lonski L, Reidenberg MM (1984) Optimizing metoclopramide control of cisplatin-induced emesis. Ann Intern Med 100: 393–395PubMedGoogle Scholar
  50. Meyers F, Stanton W, Dow G, Rocchio G (1984) Reduced adverse effects with optimal anti-emetic dosage schedule of delta-9-tetrahydrocannabinol. Proc ASCO 3: C - 366Google Scholar
  51. Moertel CG, Reitemeier RJ (1973) Controlled studies of metopimazine for the treatment of nausea and vomiting. J Clin Pharmacol 13: 282–287Google Scholar
  52. Moertel CG, Reitemeier RJ, Gage RS (1963) A controlled clinical evaluation of antiemetic drugs. JAMA 186: 116–118PubMedGoogle Scholar
  53. Morran C, Smith DC, Anderson DA, McArdle CS (1979) Incidence of nausea and vomiting with cytotoxic chemotherapy. A prospective randomised trial of antiemetics. Br Med J 1: 1223–1224Google Scholar
  54. Morrow GR, Loughner JE, Bennett JM (1984) Prevalence of nausea and vomiting and other side effects in patients receiving cytoxan, methotrexate, fluorouracil therapy with and without prednisolone. Proc ASCO 3: C - 408Google Scholar
  55. Nagy CM, Fumas BE, Einhorn LH, Bond WH (1978) Nabilone antiemetic crossover study in cancer chemotherapy patients. Proc AACR 19: 30Google Scholar
  56. Neidhart JA, Gagen M, Young D, Wilson HE (1981) Specific anti-emetics for specific cancer chemotherapeutic agents. Cancer 47: 1439–1443PubMedCrossRefGoogle Scholar
  57. Orr LE; Mckernan JF, Bloome B (1980) Antiemetic effect of tetrahydrocannabinol compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. Arch Intern Med 140: 1431–1433PubMedCrossRefGoogle Scholar
  58. Penta J, Poster D, Bruno S (1983) The pharmacological treatment of nausea and vomiting caused by cancer chemotherapy — a review. In: Laszlo J (ed) Antiemetics and cancer chemotherapy. Williams and Wilkins, Baltimore, pp 81–82Google Scholar
  59. Peroutka SJ, Snyder SH (1982) Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet 1: 658–659PubMedCrossRefGoogle Scholar
  60. Roberts WS, Wisniewski BJ, Cavanaugh D, Marsden DE (1984) Intravenous droperidol versus chlorpromazine-promethazine suppositories for the control of cis-platinum induced nausea and vomiting. Proc ASCO 3: C - 419Google Scholar
  61. Roche H, Hyman G, Nahas G, Stoopler M, Ellison RR (1984) Unexpected efficacy of prochlorperazine i.v. in preventing cisplatin-induced emesis. Proc ASCO 3: C - 420Google Scholar
  62. Sallan SE, Cronin C, Zelan M, Zinberg NE (1980) Antiemetics in patients receiving chemotherapy for cancer. A randomised comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med 302: 135–138PubMedCrossRefGoogle Scholar
  63. Sawicka J, Sallan S (1977) Transdermal therapeutic system scopolamine: prevention of vomiting associated with cancer chemotherapy. Proc ASCO 18: 302Google Scholar
  64. Schurig JE, Florczyk AP, Rose, WC, Bradner WT (1982) Antiemetic activity of butorphanol against cis-platinum induced emesis in ferrets and dogs. Cancer Treat Rep Oct; 66 (10): 1831–8Google Scholar
  65. Stambaugh JE, McAdams J, Vreeland F (1982) A phase II randomised trial of the antiemetic activity of levonantrodol in cancer patients receiving chemotherapy. Proc ASCO 1: 62Google Scholar
  66. Sridhar KS, Donnelly E, Rosenfeld C (1984) Combination antiemetic regimen including diphenhydramine, droperidol, metoclopramide and dexamethasone in cis-platin based chemotherapy regimens. Proc ASCO 3: C - 388Google Scholar
  67. Steele N, Gralla RJ, Braun DW (1980) Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treat Rep 64: 219–224PubMedGoogle Scholar
  68. Strum SB, McDermed JE, Streng B, McDermott N (1984) Combination metoclopramide and dexamethasohe — an effective antiemetic regimen in outpatients receiving doxorubicin/cyclophosphamide chemotherapy. Proc ASCO 3: C - 411Google Scholar
  69. Swann IL, Thompson EN, Quershi K (1979) Domperidone or metoclopramide in preventing chemotherapeutically induced nausea and vomiting. Br Med J 2: 11–88CrossRefGoogle Scholar
  70. Tyson LB, Gralla RJ, Clark RA, Kris MG, Bosl GJ, Reich LM, Young CW (1984a) High dose oral metoclopramide: dose-finding efficacy and preliminary pharmacokinetic evaluation. Proc ASCO 3:99–397Google Scholar
  71. Tyson LB, Stockdale AD, Bolton JAR, Kang AA, Retsas S (1984b) Antiemetic prophylaxis with high dose metoclopramide or lorazepam in vomiting induced by chemotherapy. Br Med J 288:18–79CrossRefGoogle Scholar
  72. Vincent BJ, McQuiston DJ, Einhorn LH, Nagy CM, Brames MJ (1983) Review of cannabinoids and their antiemetic effectiveness. Drugs 25 [Suppl 1]: 52–62PubMedCrossRefGoogle Scholar
  73. Weaving A, Bezwoda WR, Derman DP (1984) Seizures after antiemetic treatment with high dose domperidone: report of four cases. Br Med J 288: 17–28CrossRefGoogle Scholar
  74. Williams CJ, Bolton A, de Pemberton R, Whitehouse JM (1980) Antiemetics for patients treated with antitumour chemotherapy. Cancer Clin Trials 3: 363–367PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • A. L. Harris
    • 1
  • B. M. J. Cantwell
    • 2
  1. 1.Department of RadiotherapyUniversity of Newcastle-upon-Tyne,Newcastle General HospitalNewcastle-upon-TyneUK
  2. 2.Wolfson Unit of Clinical PharmacologyUniversity of Newcastle-upon-TyneUK

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