Comparison of Antiemetic Activity of Chloropromazine and High Doses of Metoclopramide in Cisplatin-Based Chemotherapy

Abstract

High dose metoclopramide and different phenothiazines are widely used antiemetics in cancer patients receiving chemotherapy. In a prospective randomized study we compared the antiemetic efficacy of high dose metoclopramide (M) and chloropromazine (C). We also tested the role of dexamethasone (D) when combined with either of these drugs. A total of 165 patients were randomly allocated to 5 groups with 33 patients in each group. Group A received only M, group B: M + D, group C: C + D, group D: M + D + C and group E: M + C. All patients received combination chemotherapy with cisplatin for the first time and were evaluated only once in order to exclude anticipatory nausea and vomiting. Patients in group C had less antiemetic protection than the other groups (p less than 0.001). Groups A, B, D, E, had more or less equal antiemetic efficacy, although the efficacy in group B was somewhat better; this difference was not statistically significant. Side-effects were minimal. Chloropromazine seemed to protect patients who received metoclopramide from extrapyramidal manifestations. In conclusion the results suggest that high dose metoclopramide has a better antiemetic effect than chloropromazine, dexamethasone is a helpful adjuvant drug when used in combination with an effective antiemetic agent, and chloropromazine and dexamethasone may prevent the extrapyramidal side-effects that can occur when metoclopramide is used as single antiemetic drug.

Antiemetic Efficacy of High-Dose Metoclopramide and Dexamethasone in Patients Receiving Cisplatin Chemotherapy: A Randomized Trial

“…The mechanism of action of corticosteroids remains unclear, although an antiprostaglandin effect has been suggested [24] and 20% of patients may benefit from them [13,16]. Several investigators have reported improved antiemetic efficacy of MCP plus DXM compared to MCP alone [13,14],…”

“…It is known that the effective regimens currently available contain MCP and DXM [13,17,18], with or without other agents [ 10,13]. So in our study we kept the quantity of DXM constant, and increased the amount of MCP slightly, using usual therapeutic doses, to try to study the interaction between the two agents.…”

“…To try to increase the antiemetic efficacy of MCP, ad juvant drugs such as corticosteroids, phenothiazines, and benzodiazepines have been added in different combina tions to the principle drugs and seem to contribute to the antiemetic effect [8][9][10][11][12][13]. It has been established that com bination antiemetic therapy offers the best protection against emesis [8][9][10][11][12][13].…”

“…It has been established that com bination antiemetic therapy offers the best protection against emesis [8][9][10][11][12][13].…”

“…In order to potentiate the efficacy of antiemetic drugs, adjuvant drugs have been used, such as antidopaminergic, anticholinergic and antihistaminic agents, glucocorticosteroids, benzodiazepines, marijuana, and nabilone either alone or in combination [10][11][12], According to the literature, combinations of MCP and dexamethasone (DXM) may be superior to MCP alone [11][12][13][14], but the mechanism of action of corticosteroids in nausea and vomiting is still unknown. Both high-dose methylprednisone [15,16] and DXM [12,[17][18][19][20][21][22], have been used in this situation to good effect.…”