The control of acute cisplatin-induced emesis--a comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone. Granisetron Study Group.
The anti-emetic efficacy and safety of granisetron, a highly selective and potent 5-HT3 receptor antagonist, was compared with that of high-dose metoclopramide plus dexamethasone in 281 patients due to receive single-day cisplatin chemotherapy (> or = 49 mg m-2). In this single-blind, multicentre study, granisetron (40 micrograms kg-1) was administered as a single prophylactic 5-min infusion. Dexamethasone (12 mg) was administered as a 30-min infusion followed by a loading dose of 3 mg kg-1 metoclopramide. A maintenance dose of metoclopramide 4 mg kg-1 was then infused over 8 h. A single prophylactic dose of granisetron was as effective as the combination regimen in the prevention of cisplatin-induced emesis. Of 143 granisetron-treated patients, 100 (70%) were complete responders (no vomiting and no or only mild nausea) compared with 93/138 (67%) patients who received the comparator regimen. Twenty-three percent of granisetron-treated patients experienced one of more adverse events compared with 33% of patients in the comparator group. No extrapyramidal reactions were reported in the granisetron group compared with 13 in comparator-treated patients (8%). This difference was significant (P < 0.05). The commonest adverse event in the granisetron group, headache (9.8%) described by the majority of patients as mild, was significantly higher than that reported in the comparator group (3% P = 0.02). Granisetron appears to be a safe and effective agent which can be used as a single agent for the prophylaxis of cisplatin-induced emesis. The simplicity of administration, a single 5-min infusion prior to chemotherapy, and the lack of somnolence or extrapyramidal reactions offer clear advantages over the comparator combination regimen.
Chevallier
B
B
Service de Médicine Interne et Chimiothérapie, Centre Henri Becquerel, Rouen, France.
D001794:Blood Pressure / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D017829:Granisetron; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008787:Metoclopramide / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; D011674:Pulse / Q000187:drug effects
D002945:Cisplatin; D003907:Dexamethasone; D017829:Granisetron; D007191:Indazoles; D008787:Metoclopramide