Ondansetron Compared with Metoclopramide in the Control of Emesis and Quality of Life during Repeated Chemotherapy for Breast Cancer

Abstract

This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide ≥ 500 mg/m²). Patients received an intravenous dose of 16mg dexa-methasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p < 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p < 0.001). The results for nausea also revealed highly statistically significant treatment differences (p < 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p < 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with ‘none’ or ‘mild’ nausea compared with 27% of patients receiving metoclopramide (p < 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p < 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19 % of patients in the metoclopramide group and resulted in 15 % of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer. Importantly, patients given ondansetron had a superior quality of life compared with those given metoclopramide.

Methylprednisolone enhances the efficacy of ondansetron in acute and delayed cisplatin-induced emesis over at least three cycles

“…However in these two studies corticosteroids were given only on the first day of each course. The present study confirms the major antiemetic efficacy of ondansetron and corticosteroids in combination already mentioned by various authors (Roila et al, 1991;Smith et al, 1991;Soukop et al, 1992) and confirms its activity over three identical chemotherapy courses. Moreover, this combination has shown its superiority over some of the reference antiemetic regimens: metoclopramide, dexamethasone and diphenhydramine (Italian Group for Anti-emetic Research, 1992).…”

“…These results confirm two previous studies one covering three cisplatin-containing chemotherapy courses (Italian Group for Anti-emetic Research, 1993) and the other one covering six moderately emetogenic chemotherapeutic courses (Soukop et al, 1992). However in these two studies corticosteroids were given only on the first day of each course.…”

Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy

“…In trials evaluating the efficacy of anti-emetic agents during multiple cycles of moderately emetogenic chemotherapy (non-cisplatin -Blijham, 1992;Martin et al, 1992;Soukop et al, 1992;Italian Group for Antiemetic Research, 1995a;Silva et al, 1996; non-cisplatin and cisplatin < 50 mg m -2 -de Wet et al, 1993;Kaizer et al, 1994) several diversities in patient population (Blijham, 1992;Martin et al, 1992;Soukop et al, 1992;de Wet et al, 1993;Kaizer et al, 1994;Italian Group for Antiemetic Research, 1995a;Silva et al, 1996), trial methodology (Blijham, 1992;Martin et al, 1992;Soukop et al, 1992;de Wet et al, 1993;Kaizer et al, 1994;Italian Group for Antiemetic Research, 1995a;Silva et al, 1996), or statistical analyses complicate the interpretation of results. Some authors include all patients in the evaluation of anti-emetic effect during multiple cycles (Martin et al, 1992;Soukop et al, 1992;Italian Group for Antiemetic Research, 1995a;Silva et al, 1996), whereas others include only patients with 'good' anti-emetic response during the first cycle of chemotherapy (de Wet et al, 1993;Kaizer et al, 1994) or only those who requested the same anti-emetic treatment in the following cycles (Blijham, 1992). It has been stated that the Kaplan-Meier method should be used for the calculation of the overall protection during multiple cycles (De Wit et al, 1996).…”

“…In two of the studies the number of patients still at risk decreased to less than 10% in cycles 8 and 10 respectively (Blijham, 1992;de Wet et al, 1993) and in the other three (Kaizer et al, 1994;Italian Group for Antiemetic Research, 1995a;Silva et al, 1996) the efficacy was only evaluated during the first three cycles. The trials reporting decreasing efficacy of anti-emetic treatment during multiple cycles evaluated the efficacy during six cycles of chemotherapy (Martin et al, 1992;Soukop et al, 1992). As in our study, only women were included.…”

“…Conclusions are not concordant as different methodology and different statistical analyses have been used. Some studies demonstrated a decrease in antiemetic efficacy (Martin et al, 1992;Soukop et al, 1992) whereas others found sustained efficacy (Blijham, 1992;de Wet et al, 1993;Kaizer et al, 1994;Italian Group for Antiemetic Research, 1995a;Silva et al, 1996). Cyclophosphamide-containing chemotherapy during multiple cycles is widely used as adjuvant treatment in patients with breast cancer (Early Breast Cancer Trialists' Collaborative Group, 1992).…”