Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms.
The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.
Peterson
C
C
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Hursti
T J
TJ
Börjeson
S
S
Avall-Lundqvist
E
E
Fredrikson
M
M
Fürst
C J
CJ
Lomberg
H
H
Steineck
G
G
D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008558:Melphalan / Q000008:administration & dosage; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D017294:Ondansetron / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D000932:Antiemetics; D017294:Ondansetron; D003907:Dexamethasone; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan; D006854:Hydrocortisone