Adrenal function following high-dose steroids in ovarian cancer patients.
OBJECTIVE
Steroid doses similar to those used to prevent paclitaxel-associated hypersensitivity reactions and cisplatin-induced nausea have been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression. We assessed HPA function in patients receiving high-dose steroids as part of their chemotherapy regimen for epithelial ovarian cancer.


METHODS
From January to July 1994, a cross-sectional study of HPA function was performed on patients receiving dexamethasone (DEX) as part of their paclitaxel and cisplatin chemotherapy regimen (n = 9). Patients received 20 mg of DEX orally, 6 and 12 hr prior to paclitaxel (135 mg/m2) and 10-20 mg intravenously before cisplatin (50-100 mg/m2). In addition, patients received approximately 12 mg/day of DEX orally for 4 days after their chemotherapy as an antiemetic. HPA integrity was evaluated by the administration of synthetic adrenocorticotropic hormone (ACTH). The ACTH stimulation test was performed 11-19 days after the completion of the course of DEX. Patients had fasting baseline cortisol levels drawn at approximately 0800 followed by a 25-unit intravenous injection of ACTH. Post-ACTH cortisol levels were repeated at 30 and 60 min.


RESULTS
The mean (+/- SEM) fasting baseline level of cortisol was 12.4 +/- 2.3 micrograms/dl (normal, 7-23 micrograms/dl). At 30 min following ACTH administration, the mean cortisol level rose 17.1 micrograms to 29.5 +/- 1.8 micrograms/dl; at 60 min it rose 21.4 micrograms to 33.8 +/- 2.5 micrograms/dl [P < 0.001] (normal increase 9-39 micrograms). All patients demonstrated a sufficient increase in their plasma cortisol after ACTH stimulation, indicating normal HPA function on the days tested. However, there was a significant trend toward lower increases in plasma cortisol at 30 and 60 min as the interval from ACTH stimulation testing to the DEX regimen decreased (r = 0.986; P < 0.0001). The chemotherapy cycle number had no impact on cortisol response in the multivariate analysis. Based on multiple linear regression, HPA function may be suppressed for approximately 8 days, but up to 14 days from the start of this DEX regimen.


CONCLUSIONS
Current steroid regimens prescribed with chemotherapy transiently decrease HPA function, but do not appear to inhibit the HPA axis long term. HPA function may be suppressed for approximately 8 days from the commencement of chemotherapy cycles involving DEX. Patients presenting within the first 8 days of a chemotherapy cycle using steroids with symptoms attributable to HPA suppression may benefit from HPA axis testing.
Del Priore
G
G
Department of Obstetrics and Gynecology, University of Rochester School of Medicine, New York 14642, USA.
Gurski
K J
KJ
Warshal
D P
DP
Angel
C
C
Dubeshter
B
B
D000932:Antiemetics / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D016014:Linear Models; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*
D000932:Antiemetics; D003907:Dexamethasone; D006854:Hydrocortisone