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

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.

Comparison of ondansetron with metoclopramide in prevention of acute emesis associated with low dose & high dose cisplatin chemotherapy.

BACKGROUND & OBJECTIVES: Nausea and vomiting remain the most distressing side effects of cancer chemotherapy. The present study aimed to study the efficacy and tolerability of ondansetron versus (vs) metoclopramide in different dose related grades of cisplatin induced acute emesis. METHODS: A total of 137 patients were enrolled and 80 completed the study. Cisplatin 60 mg/m2 was given intravenously (iv) either as a single dose on day 1 (high dose regimen) or in three doses of 20 mg/m2 each on days 1-3 (low dose regimen) along with bleomycin +5-flurouracil in 40 patients each. Patients were 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 20 mg metoclopramide or 8 mg ondansetron orally 8 h respectively for 24 h 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. Patients were assessed for 24 h after the last cisplatin injection. RESULTS: In low dose cisplatin regimen, complete suppression of acute emesis occurred in 65 per cent patients receiving ondansetron versus 30 per cent receiving metoclopramide, while in high dose regimen, complete response rate was 20 per cent with ondansetron versus 0 per cent with metoclopramide. Dexamethasone significantly augmented the antiemetic efficacy of metoclopramide but not that of ondansetron. Protection from nausea in the acute phase was seen in 95 per cent patients receiving ondansetron vs 70 per cent receiving metoclopramide in low dose regimen. With high dose the protection rates were 90 vs 0 per cent respectively. Combination of dexamethasone + metoclopramide achieved 70 per cent protection while dexamethasone + ondansetron was effective in 90 per cent. Dropouts and withdrawals were more among patients receiving high dose cisplatin and antiemetic regimens without dexamethasone. Thirty nine adverse events were reported by 20 out of 80 patients. All adverse events were mild. INTERPRETATION & CONCLUSION: The results demonstrate dose related emetogenicity of cisplatin and superior antiemetic efficacy of ondansetron, especially against high dose cisplatin regimen. Dexamethasone potentiated efficacy of metoclopramide but not that of ondansetron. The combination of metoclopramide plus dexamethasone was found to be as efficacious as ondansetron monotherapy.