Reach further, in an Open Access Journal Endocrinology, Diabetes & Metabolism Case Reports

ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2010) 22 P29 

Benefit to risk ratio of mitotane high starting dose strategy in 22 patients with adrenocortical carcinoma (ACC): a prospective evaluation

Sophie Mauclère-Denost1, Sophie Leboulleux1, Isabelle Borget1, Abir Al Ghuzlan1, Jacques Young2, Laurence Drouard1, Angelo Paci1, Philippe Chanson2, Martin Schlumberger1 & Eric Baudin1

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Background: The benefit to risk ratio of mitotane high starting dose regimen in ACC remains unknown.

Methods: To evaluate a high starting dose strategy, we performed a single-center, prospective study with three main objectives: 1) to assess the time taken to reach a mitotane plasma level above 14 mg/l (benefit); 2) to evaluate mitotane tolerance (risk) in the first 3 months of treatment and 3) to analyse the correlation using a regression analysis test between the shortest length of time to reach the mitotane therapeutic window (1 month) and the following parameters: age, BMI, treatment for dyslipidemia, tumour weight and size, hormone production, Weiss score, ENSAT Staging and mitotane dose.

Twenty-two patients with ACC have been prospectively enrolled. Mitotane has been administrated at a starting dosage of 2–3 g/d which was rapidly increased up to the maximal tolerated dose (max 9 g/d) within 2 weeks. Plasma mitotane levels were measured monthly using HPLC.

Results: The mitotane high starting dose strategy (median 6 g/d within two weeks) allowed the therapeutic threshold of >14 mg/l to be reached at 1, 3 or 6 months in 6/22 patients (27%) 7/22 patients (32%) and 10/19 patients (53%), respectively. Finally, 16 out of 22 patients (73%) reached the therapeutic window during the total follow-up period (median, 2 months; range 1–27 months). Eleven patients (50%) interrupted transiently the treatment for toxicity. Grade 3–4 neurological or haematological toxicities were observed in three patients (13.6%). There was a tendency for an association between a concomitant lipid-lowering treatment and a shorter time for reaching mitotane therapeutic window (OR=0.143; CI 0.016–1.265; P=0.08).

Conclusions: High starting dose of mitotane allows o,p’DDD therapeutic levels to be reached within 1 month in 27% of patients with an acceptable tolerance. Lipid-lowering therapy could be associated with a shorter time to achieve mitotane therapeutic levels.

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