Dose granisetron remain effective over multiple cycles? The Granisetron Study Group.

Intravenous (i.v.) granisetron was made available to patients who had received the drug during their first course of chemotherapy and requested granisetron prophylaxis at subsequent cycles. Initially at each further cycle patients received 40 micrograms/kg in each further cycle; this was later simplified to 3 mg. 574 patients were treated with 40 micrograms/kg over 1966 cycles of emetogenic chemotherapy in study 1. 335 patients (81 of whom transferred from study 1) received 3 mg over 785 cycles in study 2. With either regimen about 60% of all patients gained complete protection of symptoms over the 24-h postchemotherapy for up to 8 cycles. Complete response was maintained at around 70% in the subgroup of patients treated with moderately emetogenic regimens. Efficacy decreased over 5 cycles of cisplatin (greater than or equal to 50 mg/m2) from approximately 59% at the first additional cycle to around 37% at the fifth. This could, in part, be explained by a reversal in the proportions of males (low risk) to females (high risk) during the study. Withdrawal was largely due to completion of chemotherapy courses; approximately 15% of patients discontinued treatment for reasons possibly related to poor emetic control and 10% for unspecified reasons. Granisetron was well tolerated and no new toxicity developed following repeated exposure. In conclusion, granisetron maintained its efficacy over repeated cycles in most patients, although some fall-off occurred with high-dose cisplatin. 40 micrograms/kg and 3 mg were equally effective.