Randomized, double-blinded, placebo-controlled trial of ondansetron plus dexamethasone with or without metoclopramide as antiemetic prophylaxis in patients receiving high-dose cisplatin in medical practice
- 346 Downloads
Ondansetron plus dexamethasone are standard antiemetic agents for highly emetogenic chemotherapy. Metoclopramide is a dopamine antagonist, which may enhance efficacy of ondansetron and dexamethasone. The objective of this study was to assess the efficacy and tolerability of metoclopramide added to standard antiemetic regimen for prophylaxis of cisplatin-induced emesis.
Patients who received ≥50 mg/m2 of cisplatin for the first time were given intravenous ondansetron and dexamethasone on day 1 and were randomized to receive either standard antiemetics (ondansetron 8 mg orally bid on days 2–5 and dexamethasone 8 mg orally bid on days 2–4) plus metoclopramide 20 mg orally qid on days 2–5 or a placebo. The primary endpoint was a complete response (CR) rate defined as no emesis and no rescue treatment over a 120-h period. Secondary endpoints included severity of nausea and vomiting, time to first emesis, quality of life, and adverse effects.
Among 162 patients, 50 patients (60%) in the metoclopramide group and 42 patients (53%) in the control group achieved CR (p = 0.36). The mean times to first emesis in the metoclopramide and control groups were 88 and 75 h, respectively (p = 0.18). The degrees of nausea and vomiting in both groups were similar. Eleven patients (13%) in the metoclopramide group and 20 (25%) in the control group required rescue treatment (p = 0.05). Quality of life and adverse effects were not different between the two groups.
The addition of metoclopramide to ondansetron plus dexamethasone reduced the use of rescue medication, but did not affect complete response rate, quality of life or adverse effects.
KeywordsEmetogenic chemotherapy Anti-emetic Metoclopramide
The study protocol was granted by the Siriraj Research Development Fund (managed by Routine to Research, R2R).
Conflicts of interest
The authors indicated no conflict of interest.
- 2.Blanchard EM, Hesketh PJ (2008) Nausea and vomiting. In: Devita VT, Lawrence TS, Rosenberg SA (eds) Cancer principles & practice of oncology, 8th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2639–2646Google Scholar
- 4.National Comprehensive Cancer Network (2009) Antiemesis. National Comprehensive Cancer Network Guideline Version 4.2009Google Scholar
- 10.Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R et al (2003) 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 21:4112–4119PubMedCrossRefGoogle Scholar
- 11.Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie MG, Eldridge K, Hipple A et al (2003) 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 97:3090–3098PubMedCrossRefGoogle Scholar
- 15.Picus J, Martin MG (2008) Gastrointestinal complications of chemotherapy. In: Perry MC (ed) The chemotherapy source book, 14th edn. Lippincott Williams & Wilkins, Philadelphia, pp 197–208Google Scholar
- 16.Roila F, Ballatori E, Angelis VD, Tonato M, Favero AD (1997) Ondansetron versus metoclopramide, both combined with dexamethasone, in prevention of cisplatin-induced delayed emesis. J Clin Oncol 15:124–130Google Scholar