Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy.
This randomized, double-blind, double-dummy parallel study compared the anti-emetic efficacy and tolerability of the serotonin antagonist granisetron with prednisolone plus the dopamine D2 antagonist metopimazine during nine cycles of moderately emetogenic chemotherapy. Chemotherapy naive women with stage I or II breast cancer scheduled to intravenous cyclophosphamide, fluorouracil and methotrexate or cyclophosphamide, epirubicin and fluorouracil every 3 weeks were included. Patients received a single intravenous dose of granisetron 3 mg or a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day. A total of 223 women were enrolled and 218 patients (97.8%) were evaluable for efficacy. Granisetron (n = 109) was superior to prednisolone plus metopimazine (n = 109) in the prophylaxis of acute nausea and vomiting during the first cycle of chemotherapy (P < 0.001) and prednisolone plus metopimazine was superior on days 2-5 (P = 0.002). Overall, granisetron was superior on days 1-5 (P = 0.009). The median number of cycles completed with granisetron was five (95% confidence interval 4-6) compared with two (95% confidence interval 2-2) for prednisolone plus metopimazine (P = 0.0019). Constipation and rash were reported more frequently with granisetron (P < 0.001 and P = 0.043 respectively) and palpitations more frequently with prednisolone plus metopimazine (P = 0.015). In conclusion, the number of cycles completed with granisetron was significantly higher than the number completed with prednisolone plus metopimazine, but the anti-emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy.
Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.
T
T
Sigsgaard
J
J
Herrstedt
L J
LJ
Andersen
H
H
Havsteen
S W
SW
Langer
A G
AG
Kjaerbøl
H
H
Lund
M
M
Kjaer
P
P
Dombernowsky
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D017829:Granisetron / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007540:Isonipecotic Acids / Q000009:adverse effects / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D003520:Cyclophosphamide; D018492:Dopamine Antagonists; D015251:Epirubicin; D005472:Fluorouracil; D005938:Glucocorticoids; D017829:Granisetron; D007540:Isonipecotic Acids; D008727:Methotrexate; D011239:Prednisolone; D012702:Serotonin Antagonists; C005260:metopimazine