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Supportive Care in Cancer

, Volume 2, Issue 3, pp 150–160 | Cite as

Antiemetics in cancer chemotherapy: historical perspective and current state of the art

  • M. Tonato
  • F. Roila
  • A. Del Favero
  • E. Ballatori
Review Article

Abstract

Chemotherapy-related nausea and vomiting can today be controlled with available antiemetics in a high percentage of patients but emesis remains a problem for some patients, with certain drugs and with repeated cycles of chemotherapy. The fundamental steps of clinical research in antiemetics towards the improvement of the control of nausea and vomiting with new drugs or combinations are presented. Special emphasis is given to cisplatin-induced nausea and vomiting because of the frequency and relevance of this phenomenon. The use of high-dose metoclopramide, its combination with steroids, and later the addition of lorazepam or diphenhydramine represented the evolving standard of the 1980s, with the level of complete protection from vomiting improving from 30%–40% to 60%–70% with the three-drug combination. The introduction of new agents such as the 5-hydroxytryptamine 3 (5-HT3) receptor antagonists has recently offered new possibilities because of their activity and lack of toxicity. In particular, the combination of ondansetron plus dexamethasone is today the most efficacious and least toxic antiemetic treatment for prevention of emesis in patients treated with a single high dose or low repeated doses of cisplatin. A comparison of different 5-HT3 antagonists, always in combination with steroids, is now considered necessary. For patients treated with moderately emetogenic chemotherapy the use of steroids can still be considered the standard treatment. In this setting, the role of 5-HT3 receptor antagonists, alone or in combination with steroids, has to be better defined through large, well-planned clinical trials, which should have a cost-effectiveness analysis as one of their goals.

Key words

Antiemetics Chemotherapy-induced emesis 

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References

  1. 1.
    Allan SG, Cornbleet MA, Warrington PS, et al (1984) Dexamethasone and high-dose metoclopramide: efficacy in controlling cisplatin induced nausea and vomiting. Br Med J 13:235–237Google Scholar
  2. 2.
    Andrews PLR, Rapeport WG, Sanger GJ (1988) Neuropharmacology of emesis induced by anti-cancer therapy. Trends Pharmacol Sci 9:334–341Google Scholar
  3. 3.
    Ballard HS, Bottino G, Bottino J (1992) Ondansetron and chest pain (letter). Lancet 340:1107Google Scholar
  4. 4.
    Basurto C, Roila F, Bracarda S, et al (1988) A double-blind trial comparing antiemetic efficacy and toxicity of metoclopramide versus methylprednisolone versus domperidone in patients receiving doxorubicin chemotherapy alone or in coimbination with other antiblastic agents. Am J Clin Oncol 11:594–596Google Scholar
  5. 5.
    Basurto C, Roila F, Del Favero A, et al (1988) A prospective randomized double-blind crossover study comparing the antiemetic activity of alizapride and metoclopramide in patients receiving cisplatin chemotherapy. Cancer Invest 6:475–479Google Scholar
  6. 6.
    Beck TM, Madajewicz S, Navari RM, et al (1992) A double-blind, stratified, randomized comparison of intravenous (iv) ondansetron administered as a multiple dose regimen versus two single dose regimens in the prevention of cisplatin-induced nausea and vomiting. Proc Am Soc Clin Oncol 11:378Google Scholar
  7. 7.
    Bécouarn Y, Bui NB, David M, et al (1986) Improved control of cis-platin-induced emesis with a combination of high doses of methylprednisolone and metoclopramide: a single-blind randomized trial. Eur J Cancer Oncol 22:1421–1424Google Scholar
  8. 8.
    Benrubi GI, Norvell M, Nuss RC, et al (1985) The use of methylprednisolone and metoclopramide in control of emesis in patients receiving cisplatin. Gynecol Oncol 21:306–313Google Scholar
  9. 9.
    Blackwell CP, Harding SM (1989) The clinical pharmacology of ondasetron. Eur J Cancer Clin Oncol 25:521–524Google Scholar
  10. 10.
    Bonneterre J, Chevallier B, Metz R, et al (1990) A randomized doubleblind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil and doxorubicin or epirubicin chemotherapy. J Clin Oncol 8:1063–1069Google Scholar
  11. 11.
    Burton G, Huang A, Lazarus H, et al (1990) A double-blind randomized comparison of three doses of i.v. ondansetron for prevention of emesis induced by multi-day cisplatin therapy. Proc Am Soc Clin Oncol 9:328Google Scholar
  12. 12.
    Castle WM, Cunningham K, Kanarek BB (1992) Ondansetron is not associated with vascular adverse events, thrombocytopenia or renal failure (letter). Ann Oncol 3:773–774Google Scholar
  13. 13.
    Chevallier B, on behalf of the Granisetron Study Group (1990) Efficacy and safety of granisetron compared with high-dose metoclopramide plus dexamethasone in patients receiving high-dose cisplatin in a single-blind study. Eur J Cancer 26 [Suppl 1]:33–36Google Scholar
  14. 14.
    Chiara S, Scarfi P, Campora E, et al (1984) Low-dose metoclopramide versus methylprednisolone in controlling chemotherapy-induced nausea and vomiting. Chemioterapia 3:333–336Google Scholar
  15. 15.
    Chiara S, Campora E, Lionetto R, et al (1987) Methylprednisolone for the control of CMF-induced emesis. Am J Clin Oncol 10:264–267Google Scholar
  16. 16.
    Coates A, Abraham S, Kaye SB, et al (1983) On the receiving end—patient perception of the side-effects of cancer chemo-therapy. Eur J Cancer Clin Oncol 19:203–208Google Scholar
  17. 17.
    Coates AS, Childs A, Cox K, et al (1992) Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron. Ann Oncol 3:719–722Google Scholar
  18. 18.
    Cognetti F, Pinnarò P, Carlini P, et al (1984) Randomized open crossover trial between metoclopramide (MCP) and dexamethasone (DXM) for the prevention of cisplatin induced nausea and vomiting. Eur J Cancer Clin Oncol 20:183–187Google Scholar
  19. 19.
    Cunningham D, Turner A, Hawthorn J, et al (1989) Ondansetron with and without dexamethasone to treat chemotherapy-induced emesis. Lancet I:1323Google Scholar
  20. 20.
    Dana BW, Everts EC, Dickinson D (1985) Dexamethasone vs placebo for cisplatin induced emesis. A randomized cross-over trial. Am J Clin Oncol 8:426–428Google Scholar
  21. 21.
    David M, Durand M, Chauvergne J, et al (1984) Cyclophosphamide, methotrexate, and 5-FU (CMF)-induced nausea and vomiting: a controlled study with high-dose metoclopramide. Cancer Treat Rep 68:921–922Google Scholar
  22. 22.
    De Haan LD, De Mulder PHM, Beex LVAM, et al (1988) The efficacy of GR38032F an antagonist of 5-hydroxytryptamine-3 (5-HT3) in the prophylaxis of cisplatin (CDDP)-induced nausea and vomiting. Eur J Cancer Clin Oncol 24:1383–1384Google Scholar
  23. 23.
    De Mulder PHM, Seynaeve C, Vermorken JAB, 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 113:8334–8340Google Scholar
  24. 24.
    Dicato M (1991) Oral treatment with ondansetron in an outpatient setting. Eur J Cancer 27 [Suppl 1]:518–519Google Scholar
  25. 25.
    Diehl V, on behalf of the Granisetron Study Group (1992) Fractionated chemotherapy—granisetron or conventional antiemetics? Eur J Cancer 28A [Suppl 1]:21–28Google Scholar
  26. 26.
    Dobrow RB, Coppock MA, Hosenpud JR (1991) Extrapyramidal reaction caused by ondansetron. J Clin Oncol 9:1921Google Scholar
  27. 27.
    D'Olimpo JT, Camacho F, Chandra P, et al (1985) Antiemetic efficacy of high-dose dexamethasone vs placebo in patients receiving cisplatin-based chemotherapy: a randomized double blind controlled clinical trial. J Clin Oncol 3:1133–1135Google Scholar
  28. 28.
    Edge SB, et al (1987) High-dose oral and intravenous metoclopramide in doxorubicin/cyclophosphamide-induced emesis. Am J Clin Oncol 10:257–263Google Scholar
  29. 29.
    Einhorn LH, Nagy C, Werner K, et al (1990) Ondansetron: a new antiemetic for patients receiving cisplatin chemotherapy. J Clin Oncol 8:731–735Google Scholar
  30. 30.
    Fetting JH, Grochow LB, Folstein MF, et al (1982) The course of nausea and vomiting after high-dose cyclophosphamide. Cancer Treat Rep 66:1487–1493Google Scholar
  31. 31.
    Fetting JH, McCarthy LE, Borison HL, et al (1982) Vomiting induced by cyclophosphamide and phosphoramide mustard in cats. Cancer Treat Rep 66:1625–1629Google Scholar
  32. 32.
    Fraschini G, Ciociola A, Esparaza L, et al (1991) Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy. J Clin Oncol 9:1268–1274Google Scholar
  33. 33.
    Frustaci S, Grattoni E, Tumolo S, et al (1986) Randomized cross-over antiemetic study in cisplatin treated patients. Comparison between high-dose IV metoclopramide and high-dose IV dexamethasone. Cancer Chemother Pharmacol 17:75–79Google Scholar
  34. 34.
    Gralla RJ (1992) Serotonin antagonist antiemetics: progress and concerns (editorial). Ann Oncol 3:677–678Google Scholar
  35. 35.
    Gralla RJ, Braun TJ, Squillante A, et al (1981) Metoclopramide: initial clinical studies of high dosage regimen in cisplatin-induced emesis. In: Poster D (ed) The treatment of nausea and vomiting induced by cancer chemotherapy. Masson, New York, pp 167–176Google Scholar
  36. 36.
    Gralla RJ, Itri LM, Piski SE, et al (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 305:905–909Google Scholar
  37. 37.
    Grunberg SM, Stevenson LL, Russell CA, et al (1989) GR38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis. J Clin Oncol 7:700–705Google Scholar
  38. 38.
    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 9:721–728Google Scholar
  39. 39.
    Hainsworth JD, Omura GA, Khoiasteh A, et al (1991) Ondansetron (GR38032F): a novel antiemetic effective in patients receiving a multiple-day regimen of cisplatin chemotherapy. Am J Clin Oncol 14:336–340Google Scholar
  40. 40.
    Hawthorne J, Cunningham D (1990) Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret. Br J Cancer 61:56–60Google Scholar
  41. 41.
    Hesketh PJ, Murphy WK, Lester EP, et al (1989) GR38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis. J Clin Oncol 7:700–705Google Scholar
  42. 42.
    Hesketh PJ, Twaddell T, Finn A (1990) A possible role for cisplatin in the transient hepatic enzyme elevations noted after ondansetron administration. Proc Am Soc Clin Oncol 9:323Google Scholar
  43. 43.
    Higgins GA, Kilpatrick GJ, Bruce KT, et al (1989) 5-HT3 receptor antagonists injected into the area postrema inhibit cisplatin-induced emesis in the ferret. Br J Pharmacol 97:247–255Google Scholar
  44. 44.
    Homesley HD, Gainey JM, Jobson VN, et al (1982) Double-blind placebo-controlled study of metoclopramide in cisplatin-induced emesis. N Engl J Med 307:250–251Google Scholar
  45. 45.
    Italian Group for Antiemetic Research (1992) Ondansetron+dexamethasone vs metoclopramide+dexamethasone+diphenhydramine in prevention of cisplatin-induced emesis. Lancet 340:96–99Google Scholar
  46. 46.
    Jones AL, Hill AS, Soukop M, et al (1991) Comparison of ondansetron vs dexamethasone in the prophylaxis of emesis induced by moderately emetogenic chemotherapy. Lancet 338:483–487Google Scholar
  47. 47.
    Jordan NS, Schauer PK, Schauer A, et al (1985) The effect of administration rate of cisplatin induced emesis. J Clin Oncol 3:559–561Google Scholar
  48. 48.
    Joss RA, Galeazzi RL, Bischoff AK, et al (1986) The antiemetic activity of high-dose alizapride and high-dose metoclopramide in patients receiving cancer chemotherapy: a prospective, randomized, double-blind trial. Clin Pharmacol Ther 39:619–624Google Scholar
  49. 49.
    Kaasa S, Kvalov S, Dicato MA, et al (1990) A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, doubleblind study. Eur J Cancer 26:311–314Google Scholar
  50. 50.
    Kris MG, Tyson LB, Gralla RJ, et al (1983) Extrapyramidal reactions with high-dose metoclopramide. N Engl J Med 309:433Google Scholar
  51. 51.
    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 55:527–534Google Scholar
  52. 52.
    Kris MG, Gralla RJ, Clark RA, et al (1987) Antiemetic control and prevention of side efects of anticancer therapy with lorezapam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial. Cancer 60:2816–2822Google Scholar
  53. 53.
    Kris MG, Gralla RJ, Clark RA, et al (1988) Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. J Clin Oncol 6:659–662Google Scholar
  54. 54.
    Kris MG, Gralla RJ, Clark RA, et al (1989) Phase II trials of the serotonin antagonist GR38032F for the control of vomiting caused by cisplatin. J Natl Cancer Inst 81:42–46Google Scholar
  55. 55.
    Lane M, Grunberg SM, Lester EP, et al (1990) A double-blind comparison of three dose levels of i.v. ondansetron in the prevention of cisplatin-induced nausea and vomiting. Proc Soc Clin Oncol 9:329Google Scholar
  56. 56.
    Markman M, Sheidler V, Ettinger DS, et al (1984) Antiemetic efficacy of dexamethasone. Randomized, double-blind, crossover study with prochlorperazine in patients receiving cancer chemotherapy. N Engl J Med 311:549–552Google Scholar
  57. 57.
    Marschner NW, Adler M, Nagel GA, et al (1991) Double-blind randomized trial of the antiemetic efficacy and safety of ondansetron and metoclopramide in advanced breast cancer patients treated with epirubicin and cyclophosphamide. Eur J Cancer 27:1137–1140Google Scholar
  58. 58.
    Marty M, Droz JP, Pouillart P, et al (1989) GR38032F, a 5HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting. Cancer Chemother Pharmacol 23:389–391Google Scholar
  59. 59.
    Marty M, on behalf of the Granisetron Study Group (1990) A comparative study of the use of granisetron, a selective 5-HT3 antagonist, versus a standard anti-emetic regimen of chloropromazine plus dexamethasone in the treatment of cytostatic-induced emesis. Eur J Cancer 26 [Suppl 1]: 28–32Google Scholar
  60. 60.
    Marty M, d'Allens H, et le Groupe Multicentrique Francais (1990) Etude randomisée en double-insu comparant l'efficacité de l'ondansetron selon deux modes d'administration: injection unique et perfusion continue. Cah Cancer 2:541–546Google Scholar
  61. 61.
    Marty M, Pouillart P, School S, et al (1990) Comparison of the 5-hydroxytryptamine 3 (serotonin) antagonist ondansetron (GR38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. N Engl J Med 322:816–821Google Scholar
  62. 62.
    Mellink WA, Blinihim GH, Van Deyk WA (1984) Amitriptyline plus fluphenazine to prevent chemotherapy-induced emesis in cancer patients: a double-blind randomized cross-over study. Eur J Cancer Clin Oncol 20:1147–1150Google Scholar
  63. 63.
    Metz CA, Freedman RS, Magrina JF (1987) Methylprednisolone in cisplatin induced nausea and emesis: a placebo-controlled trial. Gynecol Oncol 27:84–89Google Scholar
  64. 64.
    Morran C, Smith DC, Anderson DA, et al (1979) Incidence of nausea and vomiting with cytotoxic chemotherapy. A prospective randomized trial of antiemetics. Br Med J 1:1323–1324Google Scholar
  65. 65.
    Peroutka SJ, Snyder SH (1982) Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet I:658–659Google Scholar
  66. 66.
    Pollera CF, Nardi M, Marolla P, et al (1989) Effective control of CMF-related emesis with high-dose dexamethasone: results of a double-blind crossover trial with metoclopramide and placebo. Am J Clin Oncol 12:524–529Google Scholar
  67. 67.
    Roila F, Tonato M, Basurto C, et al (1985) Antiemetic activity of two different high doses of metoclopramide in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research. Cancer Treat Rep 69:1353–1357Google Scholar
  68. 68.
    Roila F, Tonato M, Basurto C, et al (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 5:141–149Google Scholar
  69. 69.
    Roila F, Tonato M, Basurto C, et al (1987) Double-blind controlled trial of the antiemetic efficacy and toxicity of methylprednisolone (MP), metoclopramide (MTC) and domperidone (DMP) in breast cancer patients treated with iv CMF. Eur J Cancer Clin Oncol 23:615–617Google Scholar
  70. 70.
    Roila F, Basurto C, Minotti V, et al (1988) Methylprednisolone versus metoclopramide for prevention of nausea and vomiting in breast cancer patients treated with intravenous cyclophosphamide, methotrexate, 5-fluorouracil: a double-blind randomized study. Oncology 45:346–349Google Scholar
  71. 71.
    Roila F, Tonato M, Basurto C, et al (1989) Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone versus metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian Oncology Group for Clinical Research. J Clin Oncol 7:1693–1700Google Scholar
  72. 72.
    Roila F, Bracarda S, Tonato M, et al (1990) Ondansetron (GR38032F) in the prophylaxis of acute and delayed cisplatin0induced emesis. Clin Oncol 2:268–272Google Scholar
  73. 73.
    Roila F, Basurto C, Bracarda S, et al (1991) Double-blind crossover trial of single vs divided dose of metoclopramide in a combined regimen for treatment of cisplatin-induced emesis. Eur J Cancer 27:119–121Google Scholar
  74. 74.
    Roila F, Tonato M, Cognetti F, et al (1991) Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol 9:675–678Google Scholar
  75. 75.
    Roila F, Tonato M, Del Favero A (1991) Publication of unethical studies on the treatment of chemotherapy-induced emesis. J Clin Oncol 9:891Google Scholar
  76. 76.
    Saller R, Hellenbrecht D (1985) Comparison of the antiemetic efficacy of two high-dose benzamides, metoclopramide and alizapride, against antiemetic-induced emesis. Cancer Treat Rep 69:1301–1303Google Scholar
  77. 77.
    Schallier D, Van Belle S, De Greve J, et al (1985) Methylprednisolone as an antiemetic drug. A randomized double blind study. Cancer Chemother Pharmacol 14:235–237Google Scholar
  78. 78.
    Seynaeve C, Schuller J, Buser K, et al (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, randomized, parallel group study. Br J Cancer 66:192–197Google Scholar
  79. 79.
    Shinkai T, Saii N, Eguchi K, et al (1986) Antiemetic efficacy of high-dose intravenous metoclopramide and dexamethasone in patients receiving cisplatin-based chemotherapy: a randomized controlled trial. Jpn J Clin Oncol 16:279–287Google Scholar
  80. 80.
    Sledge GW, Einhorn LH, Nagy C, et al (1990) Randomized trial of ondansetron and metoclopramide as antiemetic therapy for cisplatin-based chemotherapy. Proc Am Soc Clin Oncol 9:323Google Scholar
  81. 81.
    Smaldone L, Al-Sarraf M, Aapro M, et al (1991) Randomized double-blind crossover comparison of batanopride (BMY-25801) and metoclopramide (MTC) in patients receiving cisplatinbased chemotherapy. Proc Am Soc Clin Oncol 10:342Google Scholar
  82. 82.
    Smaldone L, Murphy R, Gralla R, et al (1991) Antiemetic activity of batanopride (BMY-25801) in patients receiving cisplatin: a randomized double-blind parallel comparison of two doses. Proc Am Soc Clin Oncol 10:326Google Scholar
  83. 83.
    Smith DB, Newlands ES, Spruyt OW, et al (1990) Ondansetron (GR38032F) plus dexamethasone: effective anti-emetic prophylaxis for patients receiving cytotoxic chemotherapy. Br J Cancer 61:323–324Google Scholar
  84. 84.
    Smith DB, Newlands ES, Rustin GJS, et al (1991) Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Lancet 338:487–490Google Scholar
  85. 85.
    Smith IE, on behalf of the Granisetron Study Group (1990) A comparison of two dose levels of granisetron in patients receiving moderately emetogenic cytostatic chemotherapy. Eur J Cancer 26 [Suppl 1]:19–23Google Scholar
  86. 86.
    Smith RH (1989) Safety of ondansetron. Eur J Cancer Clin Oncol 25:547–550Google Scholar
  87. 87.
    Smyth JF, Coleman RE, Nicolson M, et al (1991) Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron? Br Med J 303:1423–1426Google Scholar
  88. 88.
    Sorbe B, Frankendal B, Glimelius B, et al (1990) A multicentre randomized study comparing the anti-emetic effects of the 5-HT3 antagonist IC5 205-930 with a metoclopramide-containing anti-emetic cocktail in patients receiving cisplatin chemotherapy. Ann Oncol 1 [Suppl]:113Google Scholar
  89. 89.
    Soukop M, on behalf of the Granisetron Study Group (1990) A comparison of two dose levels of granisetron in patients receiving high-dose cisplatin. Eur J Cancer 26 [Suppl 1]:15–19Google Scholar
  90. 90.
    Strum SB, McDermed JE, Liponi DF (1985) High-dose intravenous metoclopramide vs combination high-dose metoclopramide and intravenous dexamethasone in preventing cisplatin-induced nausea and emesis: a single-blind cross-over comparison of antiemetic efficacy. J Clin Oncol 3:245–251Google Scholar
  91. 91.
    Tonato M, Roila F, Del Favero A (1991) Methodology of antiemetic trials: a review. Ann Oncol 2:107–114Google Scholar
  92. 92.
    Tyers MD, Bunce KT, Humphrey PPA (1989) Pharmacological and antiemetic properties of ondansetron. Eur J Cancer Clin Oncol 25 [Suppl 1]:15–19Google Scholar
  93. 93.
    Venner P, for the clinical trials group of National Cancer Institute of Canada (1990) Granisetron for high dose cisplatin induced emesis: a randomized double blind study. Proc Am Soc Clin Oncol 9:320Google Scholar
  94. 94.
    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 83:1169–1173Google Scholar
  95. 95.
    Weissbach L, for the Multi-day Cisplatin Emesis Study Group (1991) Ondansetron. Lancet 338:753Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • M. Tonato
    • 1
  • F. Roila
    • 1
  • A. Del Favero
    • 2
  • E. Ballatori
    • 3
  1. 1.Division of Medical OncologyPoliclinicoPerugiaItaly
  2. 2.Institute of Internal Medicine IUniversity of PerugiaPerugiaItaly
  3. 3.Institute of StatisticsUniversity of PerugiaPerugiaItaly

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