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Artigo Produção Nacional Revisado por pares
BIBTEX RIS

Mitotane Associated With Cisplatin, Etoposide, and Doxorubicin in Advanced Childhood Adrenocortical Carcinoma

2006; Lippincott Williams & Wilkins; Volume: 28; Issue: 8 Linguagem: Inglês

10.1097/01.mph.0000212965.52759.1c

ISSN

1536-3678

Autores

Patrícia Zancanella, Mara Albonei Dudeque Pianovski, Brás Heleno de Oliveira, Sima Ferman, Gislaine Custodio Custodio Piovezan, Leniza L. Lichtvan, Suely Z. Voss, Sérvio Túlio Stinghen, Luiz G. Callefe, Guilherme A. Parise, Maria Helena Andrade Santana, Bonald C. Figueiredo,

Tópico(s)

Cancer, Hypoxia, and Metabolism

Resumo

Purpose To define a mitotane dose for pediatric patients with adrenocortical cancer (ACC) that maintains therapeutic plasma levels (TL) between 14 and 20 μg/mL and to verify its antitumor efficacy in association with 8 cycles of cisplatin, etoposide, and doxorubicin (CED). Methods Powdered mitotane was dissolved in a medium chain triglyceride oil and administered to 11 children with ACC (2.4 to 15.4 y of age); an initial low dose was increased to 4 g/m2/d. Ten of the 11 children had a germline TP53 R337H mutation. Mitotane plasma levels were determined using high-performance liquid chromatography. Results The mitotane dose to maintain TL in 7 patients ranged from 1.0 to 5.3 g/m2/d. Six children reached mitotane levels of 10 μg/mL in 3.6 months (1.5 to 5.0 mo), whereas 5 children took 8 months (6.5 to 12.5 mo). Minor to partial tumor remission was found in 5 patients (<1 y) and complete remission was found in 2 patients. Of the 3 patients who are alive at the time of report, 1 patient has been without disease for 16 months, and 2 patients have progressive disease. All patients had recurrent metastatic disease (2 to 9 times). Mitotane toxic effects were nausea, diarrhea, vomiting, neurologic alterations, gynecomastia, a rare case of hypertensive encephalopathy, and CED-related hematologic toxic effects. Conclusions Mitotane daily dose to maintain TL is variable and monitoring should start 1.5 months after the beginning of treatment. CED combined with mitotane is the best available pharmacologic treatment for ACC, but further studies are required to characterize different profiles of therapeutic response.

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