Comparison of intermittent versus continuous infusion metoclopramide in control of acute nausea induced by cisplatin chemotherapy.

Abstract

Sixty previously untreated patients with newly diagnosed advanced-stage lung cancer (21 small-cell, 39 non-small-cell) received chemotherapy with cisplatin and etoposide. Bleomycin was also used in the patients with non-small-cell lung cancer. During the first cycle of chemotherapy, 30 patients received antiemetic therapy with intermittent metoclopramide (regimen A), and the other 30 patients received continuous infusion metoclopramide (regimen B). During the second course of chemotherapy, patients were switched to the alternate regimen. Regimen A consisted of lorazepam, 1 mg, orally; dexamethasone, 10 mg, intravenously (IV) every four hours for three doses; diphenhydramine, 0.5 mg/kg, IV every four hours for three doses; metoclopramide, 1 mg/kg, IV bolus every two hours for six doses. Regimen B was identical to A except metoclopramide was administered as 1 mg/kg, IV bolus followed by 0.5 mg/kg/h for ten hours. Fifty-eight patients completed both antiemetic regimens. Thirty-nine of the 58 patients had total control of acute nausea and vomiting (0-1 episodes) with regimen A or B. Fourteen patients had poor control of acute nausea and vomiting (more than one episode) with regimen A but total control with regimen B. Five patients had poor control with either regimen. Dystonic reactions, akathisia, or diarrhea occurred in 20 of the 58 patients on regimen A, but in only eight of the 58 patients on regimen B. Compared with intermittent bolus, continuous infusion metoclopramide is more effective in total control of acute nausea and vomiting and has less toxicity.

Reducing Chemotherapy-Induced Nausea and Vomiting Current Perspectives and Future Possibilities

“…The results of comparative studies between continuous intravenous infusion and repeated bolus injection regimens often gave contrasting results regarding efficacy, toxicity and preference expressed by the patients (Agostinucci et al 1986;Danaet al 1987;Navari 1989;Ribelles et al 1991;Saito et al 1992;Warrington et al 1986;Weiss et al 1987). However, the most convincing evidence that emerges from these studies suggests that no substantial difference in efficacy or tolerability exists between continuous or repeated bolus infusion of metoclopramide, making bolus administration preferable on the basis of its simpler schedule of administration and lower cost with respect to other doses and schedules (Roila et al 1991a).…”

Optimal Control of Acute Cisplatin-lnduced Emesis

“…resulted in a similar overall complete control rate of 60% [19,20], In a few relatively small studies the efficacy of MCP given as 1 mg/kg bolus followed by 0.5 mg/kg/h infusion for 24 h was superior to 3-5 bolus doses of 1 mg/kg i.v. every 2 h [21][22][23][24]. In an unblinded, crossover study in 58 patients given MCP with loraze pam, dexamethasone and diphenhydramine [24], the to tal control of nausea and vomiting was 65 vs. 90% in favour of the continuous infusion regimen.…”

“…every 2 h [21][22][23][24]. In an unblinded, crossover study in 58 patients given MCP with loraze pam, dexamethasone and diphenhydramine [24], the to tal control of nausea and vomiting was 65 vs. 90% in favour of the continuous infusion regimen. However, due to the limitations related to the design of this study, con clusions are difficult.…”

Methodology in Anti-Emetic Trials

“…Only after phase 1 dose-finding studies should a drug enter phase II studies to estimate its efficacy. The results of phase II studies are then used to decide whether phase III comparisons of the new drug with standard ther- [3][4][5]. It is the phase III studies where methodological issues are most prominent.…”