Antiemetic Efficacy of 2-Hour Infusion of Granisetron in Patients Receiving High - Dose Cisplatin

Kim, Seung Taek; Lee, Ji Hyun; Lee, Kyung Soo; Lee, Jung A; Kim, Hye Young; Lee, Kee Hyung

Abstract

PURPOSE: The physiologic mechanism of chemotherapy induced emesis is poorly understood, but recently it is thought to be mediated by serotonergic (5-hydroxytryptamine-3 or 5-HT3) receptars. 5-HT3 is released by enterochromaffin cells in the gastrointestinal tract, which peaks 2-6 hours after the start of chemotherapy. In this study, the granisetron, an antiemetic agent, was given over 2-hour from the start of cisplatin administration to synchronize the peak level of the drug with that of 5-HT3 release.
MATERIALS AND METHODS
Chemotherapy-naive patients undergoing their first cycle of cisplatin ( > 60 mg/m)-based chemotherapy were included. One milligram of granisetron was given intravenously 15 minutes before the start of cisplatin as a loading dose, then 2 mg was given over 2-hour starting with the cisplatin.
RESULTS
24 of 25 patients were evaluable for efficacy and safety. Fifteen (62.5%) of the 24 evaluable patients had advanced gastric carcinoma and 21 (87.5%) received FP (5-FU/ Cisplatin) combination chemotherapy. The complete response rate for acute and delayed vomiting/retching was 58.3% (10/24) and 33.3% (8/24), respectively. The median latency time to first vomiting or retching was 20.3 hours. Side effects were tolerable, but central nervous symptoms (dizziness, headache, or anxiety) and diarrhea were frequently noted.
CONCLUSION
Two-hour infusion of granisetron with the beginning of cisplatin showed no superior efficacy compared with historical controls that used bolus administration of granisetron, but somewhat more frequent central nervous system and gastrointestinal symptoms were observed.