Indian Journal of Medical Research - 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.
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Methods: A total of 80 chemotherapy nave patients with malignancy were randomized to receive cisplatin 60 mg/m^sup 2^ intravenously (iv) either as a single dose on day 1 (high dose regimen) or split into three doses of 20 mg/m^sup 2^ each on 3 days (low dose regimen) along with bleomycin 5-flurouracil 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 cispaltin 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
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 dexamethnsone combination matched the antiemetic efficacy of ondansetron monotherapy.
Key words Cisplatin * delayed emesis * dexamethasone * metoclopramide * ondansetron
Nausea and vomiting are the most distressing side effects of cytotoxic chemotherapy1. In contrast to the prolonged monophasic pattern of emesis induced by agents like cyclophosphamide, cisplatin induces a biphasic pattern of emesis. The initial phase referred to as ‘acute emesis’ is more severe and peaks over the first 6-8 h2. The second phase ‘delayed emesis’, begins after 24 h and lasts for 4-5 days. Though less severe than acute emesis, it is debilitating and more resistant to conventional antiemetics3. The overall incidence of delayed emesis and nausea has been reported to vary from 43 to 89 per cent4″6 and its intensity peaks between 24 to 72 h following cisplatin administration3.
The pathophysiology of delayed emesis in contrast to that of acute emesis is largely undefined, though response to the antiemetic medication in the acute phase is the most important predictor for delayed emesis7,8. The usual practice for prevention of delayed emesis is extended administration of the antiemetic for 4 to 5 days.
There is paucity of data on control of delayed emesis and rather inconsistent results have been reported9-11. Efficacy of 5-hydroxytryptamine (5-HT3) antagonists though established against acute emesis, is controversial against delayed emesis9-11. Moreover, there are very few studies assessing the effect of antiemetics on quality of life (QOL) of cancer patients. Further, no studies have been done to compare efficacy of antiemetics against dose related grades12′14 of delayed emesis. We have earlier reported superior antiemetic efficacy of ondansetron in comparison to metoclopramide in cisplatin induced acute emesis15. The present study compares efficacy and tolerability of ondansetron with metoclopramide in delayed emesis induced by 60 mg/m^sup 2^ cisplatin given either as a single dose (high dose regimen) or split into multiple doses of 20 mg/m^sup 2^ over three days (low dose regimen) and their effect on QOL parameter. Dexamethasone has been reported to improve the control of nausea and vomiting by the primary antiemetic and the effect of a single dose administered before cispaltin injection may persist beyond the acute phase and help in control of delayed emesis as well16″18. Therefore, the effect of addition of dexamethasone to the primary antiemetic was also assessed.
Material & Methods
The study was conducted at the Department of Radiotherapy, LokNayak Hospital and Department of Pharmacology, Maulana Azad Medical College, New Delhi, over a period of 10 months (April 1998 to February 1999). It was a randomized, observer blind, prospective, parallel group study. The study protocol was approved by the institutional ethics committee. Written informed consent was obtained from all patients before inclusion in the study.
