Efficacy & tolerability of ondansetron compared to metoclopramide in dose dependent cisplatin-induced delayed emesis.

ABSTRACT

BACKGROUND & OBJECTIVES: Delayed emesis with cisplatin is a significant problem, which is often poorly controlled with conventional antiemetics. There is a relative paucity of data on the control of delayed emesis and rather inconsistent results have been reported. The present study aimed to compare the efficacy and tolerability of ondansetron versus metoclopramide in dose related grades of cisplatin-induced delayed emesis. METHODS: A total of 80 chemotherapy naive patients with malignancy were randomized to receive cisplatin 60 mg/m2 intravenously (iv) either as a single dose on day 1 (high dose regimen) or split into three doses of 20 mg/m2 each on 3 days (low dose regimen) along with bleomycin +5- fluorouracil in 40 patients each. Patients were further randomized in each cisplatin regimen to receive either 20 mg metoclopramide (20 patients) or 8 mg ondansetron (20 patients) iv 30 min prior to cisplatin administration followed by the respective antiemetic orally 8 hourly for five days after the last cisplatin administration. Ten patients receiving high dose cisplatin in each group were also given dexamethasone 8 mg iv with the primary antiemetic. The assessment period started 24 h after last cisplatin infusion and ended at midnight on day 5. RESULTS: In low dose cisplatin regimen, complete suppression of delayed emesis occurred in 55 per cent patients receiving ondansetron and in 30 per cent patients receiving metoclopramide. Neither ondansetron nor metoclopramide could completely suppress delayed emesis in high dose cisplatin regimen. Protection from nausea in the delayed phase was seen in 85 per cent patients receiving ondansetron and in 70 per cent patients receiving metoclopramide in low dose regimen, while nausea protection rates were 70 vs 0 per cent respectively in the high dose regimen. Addition of dexamethasone to metoclopramide significantly augmented its antiemetic efficacy (P<0.02) and the combination of metoclopramide + dexamethasone was found to be as efficacious as ondansetron monotherapy. Twenty out of 80 patients reported 39 adverse events of mild intensity. No significant effects on QOL (quality of life) parameters were observed in any group over the 5-day period. INTERPRETATION & CONCLUSION: The results demonstrate that delayed emesis due to cisplatin is also dose related, and superior antiemetic efficacy of ondansetron compared to metoclopramide is maintained, though its superiority is less marked than against acute emesis. Metoclopramide and dexamethasone combination matched the antiemetic efficacy of ondansetron monotherapy.