1227 Dose-response trial across four oral doses of dolasetron (DM) for emesis prevention after moderately emetogenic chemotherapy (CT)

Abstract

This double-blind multicenter trial studied four oral doses of OM for antiemetic effectiveness in 319 predominately CT-naive cancer patients, receiving IV CT. Patients were randomized to one of four treatments: 25, 50, 100, or 200 mg of DM, 30 minutes prior to CT with doxorubicin (in combination: 25–75 mg/m2 or alone: ≥ 40 mg/m2) and/or cyclophosphamide (500–1200 mg/m2). Efficacy was compared across doses using complete response (CR: no emetic episodes [EE] and no escape medication [EM]); CR + major response (CMR: 1–2 EE and no EM); patients assessment of nausea < 5 mm = no nausea) and satisfaction with antiemetic therapy via a 100 mm visual analog scale (VAS). At 24 hours, statistically significant linear trends (P < 0.0001) were detected across the 25, 50, 100, and 200 mg doses of DM, respectively, for CR (31%, 34%, 49%, and 46%), for CMR (28%, 43%, 52%, 56%), and for CR + no nausea (20.5%, 26.5%, 37.5%, 39.7%). Lineartrends with dose were also statistically significant for patient assessment of nausea (P < 0.0006) and general satisfaction (P < 0.0009). No significant dose related trends in the incidence of headache or elevated transaminases were detected. Single oral doses of DM are effective in preventing emesis in cancer patients with excellent safety and efficacy recorded with both the 100 and 200 mg doses of dolasetron. This double-blind multicenter trial studied four oral doses of OM for antiemetic effectiveness in 319 predominately CT-naive cancer patients, receiving IV CT. Patients were randomized to one of four treatments: 25, 50, 100, or 200 mg of DM, 30 minutes prior to CT with doxorubicin (in combination: 25–75 mg/m2 or alone: ≥ 40 mg/m2) and/or cyclophosphamide (500–1200 mg/m2). Efficacy was compared across doses using complete response (CR: no emetic episodes [EE] and no escape medication [EM]); CR + major response (CMR: 1–2 EE and no EM); patients assessment of nausea < 5 mm = no nausea) and satisfaction with antiemetic therapy via a 100 mm visual analog scale (VAS). At 24 hours, statistically significant linear trends (P < 0.0001) were detected across the 25, 50, 100, and 200 mg doses of DM, respectively, for CR (31%, 34%, 49%, and 46%), for CMR (28%, 43%, 52%, 56%), and for CR + no nausea (20.5%, 26.5%, 37.5%, 39.7%). Lineartrends with dose were also statistically significant for patient assessment of nausea (P < 0.0006) and general satisfaction (P < 0.0009). No significant dose related trends in the incidence of headache or elevated transaminases were detected. Single oral doses of DM are effective in preventing emesis in cancer patients with excellent safety and efficacy recorded with both the 100 and 200 mg doses of dolasetron.