Oral Metoclopramide With or Without Diphenhydramine: Potential for Prevention of Late Nausea and Vomiting Induced by Cisplatin

Late nausea and vomiting lasting 2-7 days occurs in 20%-68% of patients receiving cisplatin. We therefore studied the effects of oral metoclopramide given at doses of 20, 50, or 100 mg four times a day for 25 doses (7 days) beginning after cisplatin to determine the maximum tolerated dose (MTD) for prophylactic oral antiemetic regimens. Patients were stratified into younger (less than or equal to 30 yr old) and older (greater than 30 yr old) groups. Dose escalation was performed without or with concomitant oral diphenhydramine. For the younger group, the MTD for metoclopramide without diphenhydramine was less than 20 mg, and the MTD with diphenhydramine was 20 mg. For the older group, the MTD without diphenhydramine was 20 mg, and the MTD with diphenhydramine was 50 mg. Extrapyramidal reactions in the younger group and agitated depression in the older group were the major dose-terminating toxic effects. Patient acceptance of these regimens was excellent.