Antiemetic combination for PAC (cisplatin-adriamycin-cyclophosphamide) chemotherapy-induced emesis in ovarian cancer

Twenty-six patients suffering from disseminated epithelial ovarian cancer (FIGO stages III and IV) under treatment with Cisplatin (80-100 mg/m2 in 8 hours) in combination on the same day with Cyclophosphamide (500 mg/m2 IV) and Adriamycin (50 mg/m2), a severely emetogenic regimen, entered a randomized, double-blind, cross-over trial comparing the antiemetic activity of high-dose IV Metoclopramide (1 mg/kg/dose X 5 doses) with that of a combination of Metoclopramide (same schedule) plus Nortriptyline (50 mg PO X 2 doses) plus Thiethylperazine (10 mg IV X 3 doses). The antiemetic combination was designed in an attempt to act simultaneously on gastrointestinal motility and neuroreceptors at the central emetic pathways (dopamine D-2, histamine H-1 and muscarinic cholinergic). This combination significantly reduced the emesis due to chemotherapy when compared with Metoclopramide alone and was also preferred by a significant number of patients after passing through both the antiemetic arms being compared.