Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center.
| Autor: | Baudry C; Department of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France., Coste J, Bou Khalil R, Silvera S, Guignat L, Guibourdenche J, Abbas H, Legmann P, Bertagna X, Bertherat J |
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| Jazyk: | angličtina |
| Zdroj: | European journal of endocrinology [Eur J Endocrinol] 2012 Oct; Vol. 167 (4), pp. 473-81. Date of Electronic Publication: 2012 Jul 19. |
| DOI: | 10.1530/EJE-12-0358 |
| Abstrakt: | Context: Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first- or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD. Objective: Evaluation of the efficacy and tolerance of mitotane in CD patients. Design and Setting: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. Main Outcome Measure: Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC). Results: Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5 ± 8.9 mg/l, with a mean daily dose of 2.6 ± 1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P<0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), P=0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery. Conclusion: Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients. |
| Databáze: | MEDLINE |
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