Efficacy and safety of granisetron (Kytril) in two special patient populations: children and adults with impaired hepatic function
Palmer, R.
Seminars in Oncology 21(3 Suppl 5): 22-25
1994
ISSN/ISBN: 0093-7754 PMID: 8042033 Document Number: 6668
The 5-HT3 receptor antagonists have redefined efficacy and safety in the treatment of chemotherapyinduced nausea and vomiting. These agents have been shown to be effective and well tolerated in patients who are undergoing antineoplastic chemotherapy but who are otherwise "normal," in patients with altered metabolism due to hepatic dysfunction, and in pediatric patients. Measurement of pharmacokinetic parameters showed considerable variability. In patients with hepatic dysfunction due to liver metastases, total clearance of granisetron was halved and area under the curve values correspondingly doubled in patients with hepatic impairment. This is not unexpected since granisetron is eliminated predominantly by oxidative metabolism, which occurs largely in the liver. There was no evidence that granisetron was less effective in preventing symptoms of nausea and vomiting induced by cytostatic drugs in patients with hepatic impairment than in patients with normal liver function. In addition, despite higher concentrations of granisetron in hepatically impaired patients, it was equally well tolerated in both groups of patients. The discovery of the antiemetic properties of 5-HT3 receptor antagonists has altered the approach to the treatment of chemotherapy-induced emesis in children. Clinical trials have shown that granisetron is a useful agent in the treatment of chemotherapy-induced emesis in children and that a dose of 10 to 40 µg/kg administered prior to chemotherapy is effective and well tolerated. Study results reviewed here have shown that granisetron is effective and well tolerated in the antiemetic treatment of pediatric cancer patients, whether they are chemotherapy naive9 or have received multiple cycles.' Granisetron remained effective when used over repeat cycles," and is effective and well-tolerated in the antiemetic treatment of children receiving moderate or highly emetogenic chemotherapy."'9 There remain children, particularly adolescents receiving cisplatin or ifosfamide, in whom granisetron effectiveness was incomplete. Further studies are needed to determine whether the addition of dexamethasone may improve efficacy, as in the case of other 5-HT3 antagonists. Although the schedule used has proven to have little influence in adults, additional research will be required to evaluate repeated doses or continuous infusion schedules in refractory pediatric patients.
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