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Comparison of Two Mitotane Starting dose Regimens in Patients with Advanced Adrenocortical Carcinoma
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2013 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 12, 2281- p.Article in journal (Refereed) Published
Abstract [en]


Mitotane is the only approved drug for treatment of adrenocortical carcinoma(ACC). Its pharmacokinetic properties are not fully elucidated and different dosing regimens have never been compared head-to-head.


To investigate the relationship between mitotane dose and plasma concentration comparing two dosing regimens.


Prospective open-label multicenter trial of a predefined duration of twelve weeks.


Forty mitotane-naïve patients with metastatic ACC were assigned to a predefined low- or high-dose regimen by the local investigator. Thirty-two could be evaluated in detail.

Main Outcome Measure:

Difference in median mitotane plasma levels between both treatment groups.


Despite a difference in mean cumulative dose (440±142g versus 272±121g), median maximum plasma levels were not significantly different between the two groups (high-dose 14.3mg/L (6.3-29.7,n=20) versus 11.3mg/L (5.5-20.0,n=12), p=0.235). Ten out of twenty patients on the high-dose regimen reached plasma concentrations ≥14mg/L after 46 days (18-81 days) compared to four of twelve patients on the low-dose regimen after 55 days (46-74 days,p=0.286). All patients who reached 14mg/L at 12 weeks displayed a level ≥4.1 mg/L on day 33 (100% sensitivity). There were no significant differences in frequency and severity of adverse events. Among patients not receiving concomitant chemotherapy mitotane exposure was higher in the high-dose group: 1013±494mg.d/L versus 555±168mg.d/L, p=0.080.


The high-dose starting regimen did neither result in significantly different mitotane levels nor in a different rate of adverse events, but concomitant chemotherapy influenced these results. Thus, for mitotane monotherapy the high-dose approach is favorable, whereas for combination therapy a lower dose seems reasonable.

Place, publisher, year, edition, pages
2013. Vol. 98, no 12, 2281- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-208545DOI: 10.1210/jc.2013-2281ISI: 000328477200048PubMedID: 24057287OAI: oai:DiVA.org:uu-208545DiVA: diva2:653001
Available from: 2013-10-02 Created: 2013-10-02 Last updated: 2014-02-05Bibliographically approved

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