Supportive Care in Cancer

, Volume 27, Issue 3, pp 895–899 | Cite as

Impact of adjuvant lorazepam with granisetron on chemotherapy-induced nausea and vomiting in pediatric patients with acute lymphoblastic leukemia

  • Akane Ono
  • Kenji KishimotoEmail author
  • Daiichiro Hasegawa
  • Ran D. Goldman
  • Yoshiyuki Kosaka
Original Article



Chemotherapy-induced nausea and vomiting (CINV) affects quality of life for patients with cancer undergoing chemotherapy. We aimed to assess the effect of lorazepam with granisetron on CINV in children with acute lymphoblastic leukemia (ALL).


We reviewed the records of 71 consecutive patients with newly diagnosed ALL who received chemotherapy including vincristine, anthracycline, and systemic steroids between January 2011 and December 2016 in our hospital. The number of chemotherapy cycles reviewed was 164. All patients received granisetron as CINV prophylaxis.


Nausea was observed in 51/71 patients (72%) and 93/164 cycles (57%). Vomiting was observed in 47/71 patients (66%) and 79/164 cycles (48%). Age and gender distribution were not significantly different between patients who received lorazepam at the initiation of the chemotherapy cycle (LZP group, n = 30) and those who did not receive lorazepam (non-LZP group, n = 134). There were no significant differences in the incidence of CIN and CIV between the LZP group and non-LZP group (CIN, 67% vs. 57%, P = 0.31; CIV, 53% vs. 47%, P = 0.98). In multivariate logistic regression, female gender and older age (> 5 years) were significant risk factors for CIV (female, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.3–5.0, P = 0.007; older age, OR 2.5, CI 1.3–4.8, P = 0.008).


We found no beneficial effect of providing lorazepam as adjuvant antiemetic for prevention of CINV in children with ALL.


Lorazepam Chemotherapy Nausea Vomiting Antiemetics 



We would like to thank the doctors and nurses of the Department of Hematology and Oncology in Hyogo Prefectural Kobe Children’s Hospital, Japan, for their support and cooperation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Hesketh PJ (2008) Chemotherapy-induced nausea and vomiting. N Engl J Med 358(23):2482–2494CrossRefGoogle Scholar
  2. 2.
    Cefalo MG, Ruggiero A, Maurizi P, Attinà G, Arlotta A, Riccardi R (2009) Pharmacological management of chemotherapy-induced nausea and vomiting in children with cancer. J Chemother 21(6):605–610CrossRefGoogle Scholar
  3. 3.
    Flank J, Robinson PD, Holdsworth M, Phillips R, Portwine C, Gibson P, Maan C, Stefin N, Sung L, Dupuis LL (2016) Guideline for the treatment of breakthrough and the prevention of refractory chemotherapy-induced nausea and vomiting in children with cancer. Pediatr Blood Cancer 63:1144–1151CrossRefGoogle Scholar
  4. 4.
    Rao KV, Faso A (2012) Chemotherapy-induced nausea and vomiting: optimizing prevention and management. Am Health Drug Benefits 5(4):232–240Google Scholar
  5. 5.
    Dupuis LL, Milne-Wren C, Cassidy M, Barrera M, Portwine C, Johnston DL, Silva MP, Sibbald C, Leaker M, Routh S, Sung L (2010) Symptom assessment in children receiving cancer therapy: the parents' perspective. Support Care Cancer 18(3):281–299CrossRefGoogle Scholar
  6. 6.
    Dupuis LL, Nathan PC (2010) Optimizing emetic control in children receiving antineoplastic therapy beyond the guidelines. Pediatr Drugs 12(1):51–61CrossRefGoogle Scholar
  7. 7.
    Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, Clark-Snow RA, Dupuis LL, Einhorn LH, Feyer P, Hesketh PJ, Jordan K, Olver I, Rapoport BL, Roscoe J, Ruhlmann CH, Walsh D, Warr D, van der Wetering M, On behalf of the participants of the MASCC/ESMO Consensus Conference Copenhagen2015 (2016) 2016 MASCC and ESMO guideline update for the prevention of chemotherapy-and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 27(supplement 5):v119–v133CrossRefGoogle Scholar
  8. 8.
    Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Somerfield MR, Lyman GH (2017) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 35(28):3240–3261CrossRefGoogle Scholar
  9. 9.
    National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Antiemesis. Version 2.2017_March 28,2017. Accessed Oct 4,2017
  10. 10.
    Takeuchi H, Saeki T, Aiba K, Tamura K, Aogi K, Eguchi K, Okita K, Kagami Y, Tanaka R, Nakagawa K, Fujii H, Boku N, Wada M, Akechi T, Udagawa Y, Okawa Y, Onozawa Y, Sasaki H, Shima Y, Shimoyama N, Takeda M, Nishidate T, Yamamoto A, Ikeda T, Hirata K (2016) Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary. Int J Clin Oncol 21(1):1–12CrossRefGoogle Scholar
  11. 11.
    Malik IA, Khan WA, Qazilbash M, Ata E, Butt A, Khan MA (1995) Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol 18(2):170–175CrossRefGoogle Scholar
  12. 12.
    Molino A, Guglielmo L, Azzolini ME, Biondani P, Capelli MC, Grandinetti A, Griso C, Martinelli G, Martini N, Zanotti R et al (1991) The antiemetic activity of high-dose metoclopramide and high-dose alizapride in combination with lorazepam in patients receiving cancer chemotherapy. A prospective, randomized, double-blind study. Oncology 48(2):111–115CrossRefGoogle Scholar
  13. 13.
    Relling MV, Mulhern RK, Fairclough D, Baker D, Pui CH (1993) Chlorpromazine with and without lorazepam as antiemetic therapy in children receiving uniform chemotherapy. J Pediatr 123(5):811–816CrossRefGoogle Scholar
  14. 14.
    Dupuis LL, Nathan PC (2003) Options for the prevention and management of acute chemotherapy-induced nausea and vomiting in children. Pediatr Drugs 5(9):597–613CrossRefGoogle Scholar
  15. 15.
    Sepúlveda-Vildósola AC, Betanzos-Cabrera Y, Lastiri GG, Rivera-Márquez H, Villasis-Keever MA, Del Angel VW, Díaz FC, López-Aguilar E (2008) Palonosetron hydrochloride is an effective and safe option to prevent chemotherapy-induced nausea and vomiting in children. Arch Med Res 39(6):601–606CrossRefGoogle Scholar
  16. 16.
    Herrstedt J, Rapoport B, Warr D, Roila F, Bria E, Rittenberg C, Hesketh PJ (2011) Acute emesis: moderately emetogenic chemotherapy. Support Care Cancer 19(Supplement 1):S15–S23CrossRefGoogle Scholar
  17. 17.
    Dupuis LL, Boodhan S, Holdsworth M, Robinson PD, Hain R, Portwine C, O’Shaughnessy E, Sung L (2013) Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer 60(7):1073–1082CrossRefGoogle Scholar
  18. 18.
    Roila F, Warr D, Aapro M, Clark-Snow RA, Einhorn L, Gralla RJ, Herrstedt J, Saito M, Tonato M (2011) Delayed emesis: moderately emetogenic chemotherapy (single-day chemotherapy regimens only). Support Care Cancer 19(Supplement 1):S57–S62CrossRefGoogle Scholar
  19. 19.
    Roila F, Warr D, Clark-Snow RA, Tonato M, Gralla RJ, Einhorn LH, Herrstedt J (2005) Delayed emesis: moderately emetogenic chemotherapy. Support Care Cancer 13(2):104–108CrossRefGoogle Scholar
  20. 20.
    Dupuis LL, Boodhan S, Holdsworth M, Robinson PD, Hain R, Portwine C, O’Shaughnessy E, Sung L. Guideline for classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients. Version date: February 28, 2013. Accessed Oct 4,2017
  21. 21.
    Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458CrossRefGoogle Scholar
  22. 22.
    Shillingburg A, Biondo L (2014) Aprepitant and fosaprepitant use in children and adolescent at an academic medical center. J Pediatr Phamacol Ther 19(2):127–131Google Scholar
  23. 23.
    Holdsworth MT, Raisch DW, Frost J (2006) Acute and delayed nausea and emesis control in pediatric oncology patients. Cancer 106:931–940CrossRefGoogle Scholar
  24. 24.
    Loeffen EAH, Kremer LCM, Mulder RL, Font-Gonzalez A, Dupuis LL, Sung L, Robinson PD, van de Wetering MD, Tissing WJE (2017) The importance of evidence-based supportive care practice guidelines in childhood cancer—a plea for their development and implementation. Support Care Cancer 25:1121–1125CrossRefGoogle Scholar
  25. 25.
    Yokoi M, Tsuji D, Suzuki K, Kawasaki Y, Nakao M, Ayuhara H, Kogure Y, Shibata K, Hayashi T, Hirai K, Inoue K, Hama T, Takeda K, Nishio M, Itoh K (2018) Genetic risk factors for chemotherapy-induced nausea and vomiting in patients with cancer receiving cisplatin-based chemotherapy. Support Care Cancer 26(5):1505–1513Google Scholar
  26. 26.
    Sekine I, Segawa Y, Kubota K, Saeki T (2013) Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci 104(6):711–717CrossRefGoogle Scholar
  27. 27.
    Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Grunberg SM (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24(18):2932–2947CrossRefGoogle Scholar
  28. 28.
    Laszlo J, Clark RA, Hanson DC, Tyson L, Crumpler L, Gralla R (1985) Lorazepam in cancer patients treated with cisplatin: a drug having antiemetic, amnesic, and anxiolytic effects. J Clin Oncol 3(6):864–869CrossRefGoogle Scholar
  29. 29.
    Razavi D, Delvaux N, Farvacques C, De BF, Van HC, Kaufman L, Derde MP, Beauduin M, Piccart M (1993) Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam. J Clin Oncol 11(7):1384–1390CrossRefGoogle Scholar
  30. 30.
    Hayashi M, Takao Y, Hata C, Teramachi H, Tsuchiya T (2010) Clonazepam use for prevention of acute and delayed vomiting induced by cisplatin-based chemotherapy for lung cancer. Biol Pharm Bull 33(11):1907–1910CrossRefGoogle Scholar
  31. 31.
    Mughal TI (1983) Improved tolerance of cytotoxic chemotherapy with lorazepam. A pilot study. Oncology 40(6):392–394CrossRefGoogle Scholar
  32. 32.
    Bowcock SJ, Stockdale AD, Bolton JA, Kang AA, Retsas S (1984) Antiemetic prophylaxis with high dose metoclopramide or lorazepam in vomiting induced by chemotherapy. Br Med J (Clin Res Ed) 288(6434):1879CrossRefGoogle Scholar
  33. 33.
    Harousseau JL, Zittoun R, Bonneterre J, Hedouin M, Ouvry J (2000) Improvement in the control of chemotherapy induced emesis with ondansetron, methylprednisolone and lorazepam combination in patients treated by a moderate emetic treatment and uncontrolled by a previous antiemetic combination. Bull Cancer 87(6):491–497Google Scholar
  34. 34.
    Ahn MJ, Lee JS, Lee KH, Suh C, Choi SS, Kim SH (1994) A randomized double-blind trial of ondansetron alone versus in combination with dexamethasone versus in combination with dexamethasone and lorazepam in the prevention of emesis due to cisplatin-based chemotherapy. Am J Clin Oncol 17(2):150–156CrossRefGoogle Scholar
  35. 35.
    Marx W, McCarthy AL, Ried K, McKavanagh D, Vitetta L, Sali A, Lohning A, Isenring E (2017) The effect of a standardized ginger extract on chemotherapy-induced nausea-related quality of life in patients undergoing moderately or highly emetogenic chemotherapy: a double blind, randomized, Placebo Controlled Trial. Nutrients 9(8):867CrossRefGoogle Scholar
  36. 36.
    Lindley CM, Hirsch JD, O’Neill CV, Transau MC, Gilbert CS, Osterhaus JT (1992) Quality of life consequences of chemotherapy-induced emesis. Qual Life Res 1(5):331–340CrossRefGoogle Scholar
  37. 37.
    Dupuis LL, Taddio A, Kerr EN, Kelly A, MacKeigan L (2006) Development and validation of the pediatric nausea assessment tool for use in children receiving antineoplastic agents. Pharmacotherapy 26(9):1221–1231CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Akane Ono
    • 1
  • Kenji Kishimoto
    • 1
    Email author
  • Daiichiro Hasegawa
    • 1
  • Ran D. Goldman
    • 2
    • 3
  • Yoshiyuki Kosaka
    • 1
  1. 1.Department of Hematology and Oncology, Children’s Cancer CenterKobe Children’s HospitalKobeJapan
  2. 2.Pediatric Research in Emergency Therapeutics ( Program, Division of Translational Therapeutics, Division of Emergency Medicine, Department of PediatricsUniversity of British ColumbiaVancouverCanada
  3. 3.Evidence to InnovationBC Children’s Hospital Research InstituteVancouverCanada

Personalised recommendations