Vicente Guillem Porta, Rafael López López, Julio Rifá Ferrer, Isidro Barneto Aranda, A. Luque, Alfredo Carrato Mena, Javier Martín Broto, Enrique Aranda Aguilar, Amalia Gómez Bernal, Severina Domínguez Fernández, Virtudes Soriano Teruel, Alvaro Rodríguez Lescure
Introduction. Effectiveness of 5-HT3 receptor antagonists in preventing cyclophosphamide-induced emesis suggests that it is mediated by serotonin release. Since urinary 5-hydroxyindoleacetic acid (5-HIAA) is not significantly increased, the mechanism of emesis induction remains poorly understood, and the usefulness of these drugs in late-onset emesis prevention remains controversial. Material and methods. In this randomised, double-blind, and placebo-controlled trial, 139 chemotherapy-naïve breast cancer patients received intravenous chemotherapy combinations containing cyclophosphamide at doses >=500 mg/m2. Total anti-emetic control was the primary efficacy parameter. On day 0 all patients received intravenous granisetron (3 mg) prior to chemotherapy. On day 1 patients were randomly assigned either to oral granisetron (1 mg bid) or to placebo, for a 2-day course. Patients remained hospitalised during the study period. Rescue therapy (up to 2 doses of i.v. granisetron 3 mg) was promptly administered should there be a second episode of vomiting. Twenty-four hour urine samples were collected on days -1 to +2, for analysis of 5-HIAA excretion. Results. Relative to the control group, significantly more patients in the oral granisetron group experienced total control of emesis on day 1 (67% versus 49%; p=0.04), on day 2 (76% versus 52%; p<0.01), and on days 1-2 (60% versus 42%; p=0.04). Excretion of 5-HIAA was significantly increased on day 0, day 1 and day 2 compared to levels on day -1 (p<0.01 for all paired comparisons). The type of chemotherapy administered and the patient's history of vomiting were the variables influencing the total control of emesis. Conclusions. Oral granisetron provided high rates of effective and safe control of late-onset emesis induced by cyclophosphamide-based chemotherapy. Urinary excretion of 5-HIAA was significantly increased during the entire emesis period.