Employment of Substandard Antiemetic Prophylaxis in Recent Trials of Chemotherapy-Induced Nausea and Vomiting

1. Coates A , Abraham S , Kaye SB , Sowerbutts T , Frewin C , Fox RM , On the receiving end—patient perception of the side-effects of cancer chemotherapy. Eur J Cancer Clin Oncol 1983; 19: 203–8.

2. de Boer-Dennert M , de Wit R , Schmitz PIM , Djontono J , v Beurden V , Stoter G . Patient perceptions of the side-effects of chemotherapy: the influence of 5HT ³ antagonists. Br J Cancer 1997; 76: 1055–61.

3. Gralla RJ , Osoba D , Kris MG , Kirkbride P , Hesketh PJ , Chinnery LW , Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. J Clin Oncol 1999; 17: 2971–94.

4. 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 1999; 56: 729–64.

5. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer (MASCC). Prevention of chemotherapy- and radiotherapy-induced emesis: results of the Perugia Consensus Conference. Ann Oncol 1998; 9: 811–9.

6. The Italian Group for Antiemetic Research. Transferability to clinical practice of the results of controlled clinical trials: the case of antiemetic prophylactic treatment for cancer chemotherapy–induced nausea and vomiting. Ann Oncol 1998; 9: 759–65.

7. Drug Utilization Review Team in Oncology (DURTO). Antiemetic prescription in Italian breast cancer patients submitted to adjuvant chemotherapy. Support Care Cancer 2003; 11: 785–9.

8. Fabi A , Barduagni M , Lauro S , Portalone L , Mauri M , Marinis F , Is delayed chemotherapy-induced emesis well managed in oncological clinical practice? An observational study. Support Care Cancer 2003; 11: 156–61.

9. Dranitsaris G , Leung P , Warr D . Implementing evidence based antiemetic guidelines in the oncology setting: results of a 4-month prospective intervention study. Support Care Cancer 2001; 9: 611–8.

10. Italian Group for Antiemetic Research. Persistence of efficacy of three antiemetic regimens and prognostic factors in patients undergoing moderately emetogenic chemotherapy. J Clin Oncol 1995; 13: 2417–26.

11. Italian Group for Antiemetic Research. Cisplatin-induced delayed emesis: pattern and prognostic factors during three subsequent cycles. Ann Oncol 1994; 5: 585–9.

12. Soukop M . Management of cyclophosphamide-induced emesis over repeat courses. Oncology 1996; 53 (suppl 1): 39–45.

13. Roila F . Control of acute cisplatin-induced emesis over repeat courses of chemotherapy. Oncology 1996; 53 (suppl 1): 65–72.

14. Ossi M , Anderson E , Freeman A . 5-HT₃ Receptor antagonists in the control of cisplatin-induced delayed emesis. Oncology 1996; 53 (suppl 1): 78–85.

15. Aspinall RL , Goodman NW . Denial of effective treatment and poor quality of clinical information in placebo controlled trials of ondansetron for postoperative nausea and vomiting: a review of published trials. BMJ 1995; 311: 844–6.

16. Citron ML . Placebos and principles: a trial of ondansetron. Ann Intern Med 1993; 118: 470–1.

17. Kris MG , Cubeddu LX , Gralla RJ , Cupissol D , Tyson LB , Venkatraman E , Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin. Cancer 1996; 78: 2193–8.

18. Holdsworth MT . Ethical issues regarding study designs used in serotonin-antagonist drug development. Ann Pharmacother 1996; 30: 1182–4.

19. Abang AM , Takemoto MH , Pham T , Mandanas RA , Roy V , Selby GB , Efficacy and safety of oral granisetron versus i.v. granisetron in patients undergoing peripheral blood progenitor cell and bone marrow transplantation. Anticancer Drugs 2000; 11: 137–42.

20. Slaby J , Trneny M , Prochazka B , Klener P . Antiemetic efficacy of three serotonin antagonists during high-dose chemotherapy and autologous stem cell transplantation in malignant lymphoma. Neoplasma 2000; 47: 319–22.

21. Thongprasert S . Efficacy and tolerability of tropisetron in the prevention of cisplatin-induced nausea and vomiting in advanced non–small cell lung cancer. Acta Oncol 2000; 39: 221–4.

22. Campos D , Pereira JR , Reinhardt RR , Carracedo C , Poli S , Vogel C , Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 2001; 19: 1759–67.

23. Sigsgaard T , Herrstedt J , Handberg J , Kjaer M , Dombernowsky P . Ondansetron plus metopimazine compared with ondansetron plus metopimazine plus prednisolone as antiemetic prophylaxis in patients receiving multiple cycles of moderately emetogenic chemotherapy. J Clin Oncol 2001; 19: 2091–7.

24. Ozgur Tan M , Sandikci Z , Uygur MC , Arik AI , Erol D . Combination of transcutaneous electrical nerve stimulation and ondansetron in preventing cisplatin-induced emesis. Urol Int 2001; 67: 54–8.

25. Cocquyt V , Van Belle S , Reinhardt RR , Decramer ML , O'Brien M , Schellens JH , Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis. Eur J Cancer 2001; 37: 835–42.

26. Feng F , Zhang P , He Y , Li Y , Zhou M , Chen G , Clinical comparison of the selective serotonin₃ antagonists ramosetron and granisetron in treating acute chemotherapy-induced emesis, nausea and anorexia. Chin Med Sci J 2002; 17: 168–72.

27. Kang YK , Park YH , Ryoo BY , Bang YJ , Cho KS , Shin DB , Ramosetron for the prevention of cisplatin-induced acute emesis: a prospective randomized comparison with granisetron. J Int Med Res 2002; 30: 220–9.

28. Lehoczky O , Udvary J , Pulay T . Freeze dried ondansetron: first observations with the fast dissolving oral antiemetic Zofran Zydis for the prophylaxis of the cisplatin-induced emesis in gynecological cancer patients. Neoplasma 2002; 49: 126–8.

29. Noda K , Ikeda M , Yoshida O , Yano S , Taguchi T , Shimoyama T , Clinical evaluation of ramosetron injections in the treatment of cisplatin-induced nausea and vomiting. J Int Med Res 2002; 30: 211–9.

30. Van Belle S , Lichinitser MR , Navari RM , Garin AM , Decramer ML , Riviere A , Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer 2002; 94: 3032–41.

31. Carmichael J , Harris AL . High-dose i.v. granisetron for the prevention of chemotherapy-induced emesis: cardiac safety and tolerability. Anticancer Drugs 2003; 14: 739–44.

32. Koizumi W , Tanabe S , Nagaba S , Higuchi K , Nakayama N , Saigenji K , A double-blind, crossover, randomized comparison of granisetron and ramosetron for the prevention of acute and delayed cisplatin-induced emesis in patients with gastrointestinal cancer: is patient preference a better primary endpoint? Chemotherapy 2003; 49: 316–23.

33. Sagae S , Ishioka S , Fukunaka N , Terasawa K , Kobayashi K , Sugimura M , Combination therapy with granisetron, methylprednisolone and droperidol as an antiemetic prophylaxis in CDDP-induced delayed emesis for gynecologic cancer. Oncology 2003; 64: 46–53.

34. Streitberger K , Friedrich-Rust M , Bardenheuer H , Unnebrink K , Windeler J , Goldschmidt H , Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial. Clin Cancer Res 2003; 9: 2538–44.

35. Eisenberg P , MacKintosh FR , Ritch P , Cornett PA , Macciocchi A . Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogenic cisplatin-based chemotherapy: a dose-ranging clinical study. Ann Oncol 2004; 15: 330–7.

36. Villalon A , Chan V . Multicenter, randomized trial of ramosetron plus dexamethasone versus ramosetron alone in controlling cisplatin-induced emesis. Support Care Cancer 2004; 12: 58–63.

37. Fauser AA , Pizzocaro G , Schueller J , Khayat D , Wilkinson P . A double-blind, randomised, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting. Support Care Cancer 2000; 8: 49–54.

38. Friedman CJ , Burris HA 3rd , Yocom K , Blackburn LM , Gruben D . Oral granisetron for the prevention of acute late onset nausea and vomiting in patients treated with moderately emetogenic chemotherapy. Oncologist 2000; 5: 136–43.

39. Hesketh PJ , Crews JR , Cohen R , Blackburn LM , Friedman CJ . Antiemetic efficacy of single-dose oral granisetron (1 mg vs 2 mg) with moderately emetogenic chemotherapy. Cancer J 2000; 6: 157–61.

40. Oge A , Alkis N , Oge O , Kartum A . Comparison of granisetron, ondansetron and tropisetron for control of vomiting and nausea induced by cisplatin. J Chemother 2000; 12: 105–8.

41. Aksoylar S , Akman SA , Ozgenc F , Kansoy S . Comparison of tropisetron and granisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy. Pediatr Hematol Oncol 2001; 18: 397–406.

42. Togo S , Akiyama H , Yamaguchi S , Ichikawa Y , Ike H , Shimada H . Clinical evaluation of granisetron as an inhibitor of nausea and vomiting induced by oral anticancer drugs. Oncol Rep 2002; 9: 277–82.

43. Numbenjapon T , Sriswasdi C , Mongkonsritragoon W , Leelasiri A , Prayoonwiwat W . Comparative study of low-dose oral granisetron plus dexamethasone and high-dose metoclopramide plus dexamethasone in prevention of nausea and vomiting induced by CHOP-therapy in young patients with non-Hodgkin's lymphoma. J Med Assoc Thai 2002; 85: 1156–63.

44. Eisenberg P , Figueroa-Vadillo J , Zamora R , Charu V , Hajdenberg J , Cartmell A , 99–04 Palonosetron Study Group. 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 2003; 98: 2473–82.

45. Gralla R , Lichinitser M , Van Der Vegt S , Sleeboom H , Mezger J , Peschel C , 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 2003; 14: 1570–7.

46. Inoue A , Yamada Y , Matsumura Y , Shimada Y , Muro K , Gotoh M , Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan. Support Care Cancer 2003; 11: 528–32.

47. Sigsgaard T , Herrstedt J , Christensen P , Andersen O , Dombernowsky P . Antiemetic efficacy of combination therapy with granisetron plus prednisolone plus the dopamine D₂ antagonist metopimazine during multiple cycles of moderately emetogenic chemotherapy in patients refractory to previous antiemetic therapy. Support Care Cancer 2000; 8: 233–7.

48. Markman M , Kennedy A , Webster K , Peterson G , Kulp B , Belinson J . The antiemetic efficacy of oral ondansetron plus intravenous dexamethasone in patients with gynecologic malignancies receiving carboplatin-based chemotherapy. Gynecol Oncol 2000; 78: 43–6.

49. Tsavaris N , Kosmas C , Vadiaka M , Kanelopoulos P , Kontos A , Katsorida M , Ondansetron and dexamethasone treatment with different dosing schedules (24 versus 32 mg) in patients with non–small-cell lung cancer under cisplatin-based chemotherapy: a randomized study. Chemotherapy 2000; 46: 364–70.

50. White L , Daly SA , McKenna CJ , Zhestkova N , Leal C , Breatnach F , A comparison of oral ondansetron syrup or intravenous ondansetron loading dose regimens given in combination with dexamethasone for the prevention of nausea and emesis in pediatric and adolescent patients receiving moderately/highly emetogenic chemotherapy. Pediatr Hematol Oncol 2000; 17: 445–55.

51. Herrington JD , Kwan P , Young RR , Lagow E , Lagrone L , Riggs MW . Randomized, multicenter comparison of oral granisetron and oral ondansetron for emetogenic chemotherapy. Pharmacotherapy 2000; 20: 1318–23.

52. Hesketh PJ , Roman A , Hesketh AM , Perez EA , Edelman M , Gandara DR . Control of high-dose-cisplatin-induced emesis with an all-oral three-drug antiemetic regimen. Support Care Cancer 2000; 8: 46–8.

53. Forni C , Ferrari S , Loro L , Mazzei T , Beghelli C , Biolchini A , Granisetron, tropisetron, and ondansetron in the prevention of acute emesis induced by a combination of cisplatin-adriamycin and by high-dose ifosfamide delivered in multiple-day continuous infusions. Support Care Cancer 2000; 8: 131–3.

54. Chua DT , Sham JS , Kwong DL , Kwok CC , Yue A , Foo YC , 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 2000; 23: 185–91.

55. Barrajon E , de las Peñas R . Randomised double blind crossover study comparing ondansetron, granisetron and tropisetron. A cost–benefit analysis. Support Care Cancer 2000; 8: 323–33.

56. Maisano R , Spadaro P , Toscano G , Caristi N , Pergolizzi S , Salimbeni V . Cisapride and dexamethasone in the prevention of delayed emesis after cisplatin administration. Support Care Cancer 2001; 9: 61–4.

57. Blaney S , Berg SL , Pratt C , Weitman S , Sullivan J , Luchtman-Jones L , A phase I study of irinotecan in pediatric patients: a Pediatric Oncology Group study. Clin Cancer Res 2001; 7: 32–7.

58. Bilgrami S , Bona RD , Edwards RL , Li Z , Naqvi B , Shaikh A , Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma. Bone Marrow Transplant 2001; 28: 137–43.

59. Tsukada H , Hirose T , Yokoyama A , Kurita Y . Randomised comparison of ondansetron plus dexamethasone with dexamethasone alone for the control of delayed cisplatin-induced emesis. Eur J Cancer 2001; 37: 2398–404.

60. Minami H , Ohtsu T , Fujii H , Igarashi T , Itoh K , Uchiyama-Kokubu N , Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance. Jpn J Cancer Res 2001; 92: 220–30.

61. de Wit R , de Boer AC , vd Linden GH , Stoter G , Sparreboom A , Verweij J . 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 2001; 85: 1099–101.

62. Fox-Geiman MP , Fisher SG , Kiley K , Fletcher-Gonzalez D , Porter N , Stiff P . Double-blind comparative trial of oral ondansetron versus oral granisetron versus IV ondansetron in the prevention of nausea and vomiting associated with highly emetogenic preparative regimens prior to stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 596–603.

63. Liaw CC , Chang HK , Liau CT , Huang JS , Lin YC , Chen JS . Reduced maintenance of complete protection from emesis for women during chemotherapy cycles. Am J Clin Oncol 2003; 26: 12–5.

64. Forni C , Loro L , Mazzei T , Beghelli C , Biolchini A , Tremosini M , Tropisetron and dexamethasone administered twice daily for the prevention of acute emesis in patients treated with continuous infusion of cisplatin–doxorubicin and high-dose ifosfamide over 48, 24, and 120 hours. Cancer Nurs 2003; 26: 331–4.

65. Aapro MS , Thuerlimann B , Sessa C , De Pree C , Bernhard J , Maibach R ; Swiss Group for Clinical Cancer Research. A randomized double-blind trial to compare the clinical efficacy of granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis. Ann Oncol 2003; 14: 291–7.

66. Chawla SP , Grunberg SM , Gralla RJ , Hesketh PJ , Rittenberg C , Elmer ME , Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 2003; 97: 2290–300.

67. Poli-Bigelli S , Rodrigues-Pereira J , Carides AD , Julie Ma G , Eldridge K , Hipple A , Aprepitant Protocol 054 Study Group. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 2003; 97: 3090–8.

68. Martin AR , Carides AD , Pearson JD , Horgan K , Elmer M , Schmidt C , Functional relevance of antiemetic control. Experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant. Eur J Cancer 2003; 39: 1395–401.

69. Hesketh PJ , Grunberg SM , Gralla RJ , Warr DG , Roila F , de Wit R , Aprepitant Protocol 052 Study Group. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study Group. J Clin Oncol 2003; 21: 4112–9.

70. de Wit R , Herrstedt J , Rapoport B , Carides AD , Carides G , Elmer M , Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 2003; 21: 4105–11.

71. Italian Group for Antiemetic Research. Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide. J Clin Oncol 2004; 22: 725–9.

72. Lehoczky O , Udvary J , Bagameri A , Pulay T . Does increasing the steroid dose enhance the efficacy of the antiemetic combination of granisetron and methylprednisolone in gynecologic cancer patients—a randomized study. Eur J Obstet Gynecol Reprod Biol 2004; 113: 94–7.

73. Minegishi Y , Ohmatsu H , Miyamoto T , Niho S , Goto K , Kubota K , Efficacy of droperidol in the prevention of cisplatin-induced delayed emesis: a double-blind, randomised parallel study. Eur J Cancer 2004; 40: 1188–92.

74. de Wit R Herrstedt J , Rapoport B , Carides AD , Guoguang-Ma J , Elmer M , The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials. Eur J Cancer 2004; 40: 403–10.

75. Bailes J . Managed care and oncology: the quality debate. J Clin Oncol 2000; 18: 705–7.

76. American Federation of Clinical Oncology Societies. Access to quality cancer care: consensus statement. J Clin Oncol 1998; 16: 1628–30.

77. Rothman KJ , Michels KB . The continuing unethical use of placebo controls. N Engl J Med 1994; 331: 394–8.

78. Enserink M . Psychiatry. Are placebo-controlled drug trials ethical? Science 2000; 288: 416.

79. Weijer C . The ethical analysis of risk. J Law Med Ethics 2000; 28: 344–61.

80. The Belmont Report: ethical principles and guidelines for the protection of human subjects of research. Washington, DC: US Government Printing Office, 1978. DHEW Publication no. (OS) 78-0012. Federal Register 1979; 44(Apr 18):23192.

81. Title 45, Code of Federal Regulations, Part 46. Protection of Human Subjects. Department of Health and Human Services; 2001. www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm (accessed 2005 Jan 18).

82. Freedman B . Equipoise and the ethics of clinical research. N Engl J Med 1987; 317: 141–5.

83. Grunberg SM , Cefalu WT . The integral role of clinical research in clinical care. N Engl J Med 2003; 348: 1386–8.

84. Joffe S , Weeks JC . Views of American oncologists about the purposes of clinical trials. J Natl Cancer Inst 2002; 94: 1847–53.

85. Miller FG , Rosenstein DL . The therapeutic orientation to clinical trials. N Engl J Med 2003; 348: 1383–6.

86. Horng S , Grady C . Misunderstanding in clinical research: distinguishing therapeutic misconception, therapeutic misestimation and therapeutic optimism. IRB: Ethics & Human Res 2003; 25: 11–6.