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.
Service de Médicine Interne et Chimiothérapie, Centre Henri Becquerel, Rouen, France.
B
B
Chevallier
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