ADRENAL-FUNCTION FOLLOWING HIGH-DOSE STEROIDS IN OVARIAN-CANCER PATIENTS

Purpose: Steroid doses similar to those used to prevent paclitaxel-ass ociated hypersensitivity reactions and cisplatin-induced nausea have b een associated with hypothalamic-pituitary-adrenal (HPA) axis suppress ion. We assessed HPA function in patients receiving high-dose steroids as part of their chemotherapy regimen for epithelial ovarian cancer, Patients and Methods: From January to July 1994, a cross-sectional stu dy 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 pac litaxel (135 mg/m(2)) and 10-20 mg intravenously before cisplatin (50- 100 mg/m(2)). In addition, patients received approximately 12 mg/day o f DEX orally for 4 days after their chemotherapy as an antiemetic, HPA integrity was evaluated by the administration of synthetic adrenocort icotropic hormone (ACTH). The ACTH stimulation test was performed 11-1 9 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 re peated at 30 and 60 min. Results: The mean (+/-SEM) fasting baseline l evel of cortisol was 12.4 +/- 2.3 mu g/dl (normal, 7-23 mu g/dl). At 3 0 min following ACTH administration, the mean cortisol level rose 17.1 mu g to 29.5 +/- 1.8 mu g/dl; at 60 min it rose 21.4 mu g to 33.8 +/- 2.5 mu g/dl [P < 0.001] (normal increase 9-39 mu g). All patients dem onstrated a sufficient increase in their plasma cortisol after ACTH st imulation, indicating normal HPA function on the days tested, However, there was a significant trend toward lower increases in plasma cortis ol at 30 and 60 min as the interval from ACTH stimulation testing to t he DEX regimen decreased (r = 0.986; P < 0.0001), The chemotherapy cyc le number had no impact on cortisol response in the multivariate analy sis. Based on multiple linear regression, HPA function may be suppress ed for approximately 8 days, but up to 14 days from the start of this DEX regimen, Conclusion: Current steroid regimens prescribed with chem otherapy transiently decrease HPA function, but do not appear to inhib it the HPA axis long term. HPA function may be suppressed for approxim ately 8 days from the commencement of chemotherapy cycles involving DE X. Patients presenting within the first 8 days of a chemotherapy cycle using steroids with symptoms attributable to HPA suppression may bene fit from HPA axis testing. (C) 1995 Academic Press, Inc.