Sains Malaysiana 50(6)(2021): 1707-1714

http://doi.org/10.17576/jsm-2021-5006-17

 

Efficacy of Granisetron in the Prevention of Nausea and Vomiting among Paediatric Oncology Patients Receiving Moderate to Highly Emetogenic Chemotherapy: A Single-Blinded, Non-Inferiority Trial

(Keberkesanan Granisetron dalam Mencegah Loya dan Muntah di Kalangan Pesakit Pediatrik Onkologi yang Menerima Kemoterapi Emetogenik Sederhana hingga Tinggi: Suatu Kajian Kesamarataan, Rabun Satu Pihak)

 

SIE CHONG DORIS LAU, CHENG KHAI SOH, C-KHAI LOH, SYED ZULKIFLI SYED ZAKARIA & HAMIDAH ALIAS*

 

Department of Paediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Kuala Lumpur, Federal Territory, Malaysia

 

Received: 18 March 2020/Accepted: 15 October 2020

 

ABSTRACT

This single-blinded, non-inferiority trial was conducted over an 8-month period to examine the efficacy of intravenous granisetron at two differing doses in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) among paediatric patients receiving moderate to highly emetogenic chemotherapy. Seventeen patients (9 males and 8 females) were recruited and randomly assigned to receive alternating granisetron dosages of 0.01 mg/kg and 0.04 mg/kg during each chemotherapy cycle. The severity of CINV during and three days post-completion of chemotherapy, as well as common side effects of granisetron were recorded. A total of 78 cycles of chemotherapy (38 cycles of 0.01 mg/kg and 40 cycles of 0.04 mg/kg) were evaluated. The median age of the study population was 5.2 years (interquartile range 25th, 3.8; 75th, 8.7). Patients’ diagnoses comprised of haematological malignancy, bone tumour and cerebral neoplasm. From this study, we demonstrated that intravenous (IV) granisetron 0.01 mg/kg was non-inferior to 0.04 mg/kg in terms of achieving a complete response for acute CINV. However, a similar observation was not seen in the post-treatment period analysis (delayed CINV). In conclusion, IV granisetron at 0.04 mg/kg/dose provides effective protection and prophylaxis of both acute and delayed CINV. Further study with a larger sample size may be required before a definite conclusion can be made with regards to efficacy of 0.01 mg/kg dose.

 

Keywords: Chemotherapy; granisetron; nausea and vomiting; non-inferiority; paediatric

 

ABSTRAK

Kajian kesamarataan, rabun satu pihak ini dijalankan selama tempoh 8 bulan untuk melihat keberkesanan ubat granisetron intravena pada 2 dos yang berbeza dalam mencegah loya dan muntah di kalangan pesakit pediatrik yang menerima kemoterapi tahap emetogenik sederhana hingga tinggi. Tujuh belas pesakit (9 lelaki dan 8 perempuan) telah direkrut dan dibahagikan secara rawak untuk menerima dos granisetron 0.01 mg/kg dan 0.04 mg/kg secara berselang setiap kitaran kemoterapi. Tahap keterukan loya dan muntah semasa (akut) dan 3 hari selepas (tertangguh) kemoterapi, serta kesan sampingan granisetron dicatatkan. Sebanyak 78 kitaran kemoterapi (38 kitaran dengan dos 0.01 mg/kg dan 40 kitaran dengan dos 0.04 mg/kg) telah dikaji. Umur median pesakit kajian adalah 5.2 tahun (kuartil ke-25, 3.8; ke-75, 8.7). Diagnosis pesakit merangkumi kanser darah, tulang dan otak. Daripada kajian ini, kami menunjukkan bahawa granisetron intravena dos 0.01 mg/kg tidak kurang keberkesanannya apabila dibandingkan dengan dos 0.04 mg/kg untuk mencapai respons sepenuhnya bagi mencegah loya dan muntah akut. Namun, pemerhatian yang sama tidak dilihat untuk loya dan muntah tertangguh selepas kemoterapi. Kesimpulannya, dos granisetron intravena 0.04 mg/kg memberikan perlindungan dan pencegahan yang berkesan untuk loya dan muntah akut serta tertangguh. Kajian lanjut dengan saiz sampel yang lebih besar diperlukan sebelum kesimpulan yang pasti boleh dibuat mengenai keberkesanan dos 0.01 mg/kg.

 

Kata kunci: Kemoterapi; granisetron; kesamarataan; loya dan muntah; pediatrik

 

REFERENCES

Aksoylar, S., Akman, S.A., Özgenç, F. & Kansoy, S. 2001. Comparison of tropisetron and granisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy. Pediatric Hematology and Oncology 18(6): 397-406.

Baxter, A.L., Watcha, M.F., Baxter, W.V., Leong, T. & Wyatt, M.M. 2011. Development and validation of a pictorial nausea rating scale for children. Pediatrics 127(6): e1542-e1549.

Bender, C.M., McDaniel, R.W., Murphy-Ende, K., Pickett, M., Rittenberg, C.N., Rogers, M.P., Schneider, S.M. & Schwartz, R.N. 2002. Chemotherapy-induced nausea and vomiting. Clinical Journal of Oncology Nursing 6(2): 94-102.

Berrak, S.G., Ozdemir, N., Bakirci, N., Turkkan, E., Canpolat, C., Beker, B. & Yoruk, A. 2007. A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy. Supportive Care in Cancer 15(10): 1163-1168.

Dupuis, L.L. & Nathan, P.C. 2010. Optimizing emetic control in children receiving antineoplastic therapy beyond the guidelines. Pediatric Drugs 12(1): 51-61.

Dupuis, L.L., Sung, L., Molassiotis, A., Orsey, A.D., Tissing, W. & van de Wetering, M. 2017. 2016 updated MASCC/ESMO consensus recommendations: Prevention of acute chemotherapy-induced nausea and vomiting in children. Supportive Care in Cancer 25(1): 323-331.

Dupuis, L.L., Boodhan, S., Holdsworth, M., Robinson, P.D., 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. Pediatric Blood & Cancer 60(7): 1073-1082.

Dupuis, L.L., Boodhan, S., Sung, L., Portwine, C., Hain, R., McCarthy, P. & Holdsworth, M. 2011. Guideline for classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients. Pediatric Blood & Cancer           57(2): 191-198.

Emir, S., Erturgut, P. & Vidinlisan, S. 2013. Comparison of granisetron plus dexamethasone versus an antiemetic cocktail containing midazolam and diphenhydramine for chemotherapy induced nausea and vomiting in children. Indian Journal of Medical and Paediatric Oncology 34(4): 270-273.

Flank, J., Robinson, P.D., Holdsworth, M., Phillips, R., Portwine, C., Gibson, P., Maan, C., Stefin, N., Sung, L. & Dupuis, L.L. 2016. Guideline for the treatment of breakthrough and the prevention of refractory chemotherapy-induced nausea and vomiting in children with cancer. Pediatric Blood & Cancer 63(7): 1144-1151.

Hählen, K., Quintana, E., Pinkerton, C.R. & Cedar, E. 1995. A randomized comparison of intravenously administered granisetron versus chlorpromazine plus dexamethasone in the prevention of ifosfamide-induced emesis in children. The Journal of Pediatrics 126(2): 309-313.

Hesketh, P.J. 2008. Chemotherapy-induced nausea and vomiting. New England Journal of Medicine 358(23): 2482-2494.

Jaing, T.H., Tsay, P.K., Hung, I.J., Yang, C.P. & Hu, W.Y. 2004. Single-dose oral granisetron versus          multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia. Pediatric Hematology and Oncology 21(3): 227-235.

Komada, Y., Matsuyama, T., Takao, A., Hongo, T., Nishimura, Y., Horibe, K. & Sakurai, M. 1991. A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy. European Journal of Cancer 35(7): 1095-1101.

Lemerle, J., Amaral, D., Southall, D.P., Upward, J. & Murdoch, R.D. 1991. Efficacy and safety of granisetron in the prevention of chemotherapy-induced emesis in paediatric patients. European Journal of Cancer and Clinical Oncology 27(9): 1081-1083.

Mabro, M., Cohn, R., Zanesco, L., Madon, E., Hählen, K., Margueritte, G., Breatnach, F., Gentet, J.C. & Plouvier, É. 2000. Granisétron en solution buvable dans la prevention des vomissements chimio-induits de l’enfant: Comparison en double aveugle de deux posologies. Bulletin du Cancer 87(3): 259-264.

Morrow, G.R., Roscoe, J.A., Kirshner, J.J., Hynes, H.E. & Rosenbluth, R.J. 1998. Anticipatory nausea and vomiting in the era of 5-HT 3 antiemetics. Supportive Care in Cancer 6(3): 244-247.

Roscoe, J.A., Morrow, G.R., Aapro, M.S., Molassiotis, A. & Olver, I. 2011. Anticipatory nausea and vomiting. Supportive Care in Cancer 19(10): 1533-1538.

Tsuchida, Y., Hayashi, Y., Asami, K., Yamamoto, K., Yokoyama, J., Mugishima, H., Honna, T., Mimaya, J., Hara, F., Sawada, T., Matsumura, T., Suita, S., Sugimoto, T. & Kaneko, M. 1999. Effects of granisetron in children undergoing high-dose chemotherapy: A multi-institutional, cross-over study. International Journal of Oncology 14(4): 673-679.

 

*Corresponding author; email: midalias@ppukm.ukm.edu.my

 

 

 

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