Abstract 37P
Background
Mitotane is the cornerstone of both adjuvant and metastatic treatment of adrenocortical carcinoma (ACC). The side effects of this drug include those related to its estrogenic mimetic action, which has not been well studied.
Methods
We conducted a retrospective study to assess the rate of menometrorrhagia, endometrial thickness, and ovarian cysts among female ACC patients (F-ACC), as well as gynecomastia among male ACC patients (M-ACC patients) who had been taking mitotane for at least 6 months. Secondary objectives were to examine the correlation between these toxicities and possible clinical factors.
Results
35 F-ACC and 25 M-ACC patients were enrolled; of these, 22 (36.7%) F-ACC and 7 (11.7%) M-ACC patients developed mitotane-related estrogenic effects, respectively. Among F-ACCs, 10 (28.6%) had menometrorrhagia, 8 (22.9%) endometrial thickening, and 13 (37.1%) ovarian cysts. Serum levels of testosterone (p 0.006) and DHEAS (p 0.002) had an inverse correlation with these side effects, but there was no correlation with mitotane plasma concentration, duration of mitotane therapy (p 1.0) and serum levels of LH (p 0.5), FSH (p 1.0), estradiol (p 0.587), cortisol (p 0.234), ACTH (p 0.139), 17-OH progesterone (p 0.381). M-ACC patients developing gynecomastia had higher mitotane concentrations (median: 17 mg/l vs 10 mg/l, p 0.005). Whereas there was no statistically significant correlation between this side effect and serum values of estradiol (p 0.643), testosterone (p 0.222), cortisol (p 1.0), ACTH (p 0.71), 17-OH progesterone (p 0.857) and DHEAS (p 0.143).
Conclusions
Women with ACC are particularly susceptible to estrogen-mimetic side effects of mitotane, which are inversely correlated with androgen levels. Serum mitotane levels can affect men's gynecomastia.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
A. Berruti.
Funding
Has not received any funding.
Disclosure
S. Grisanti: Financial Interests, Personal, Advisory Board: Roche, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Roche, AstraZeneca. A. Berruti: Financial Interests, Personal, Advisory Board: HRA; Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Personal, Research Grant: Janssen, Sanofi, Novartis. All other authors have declared no conflicts of interest.