Mitotane associated with cisplatin, etoposide, and doxorubicin in advanced childhood adrenocortical carcinoma: mitotane monitoring and tumor regression.

PURPOSE: To define a mitotane dose for pediatric patients with adrenocortical cancer (ACC) that maintains therapeutic plasma levels (TL) between 14 and 20 microg/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 microg/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.

Linfoma De Burkitt / Burkitt's Lymphoma

Introdução: o linfoma pertence ao grupo dos linfomas não-Hodgkin, apresentando condições malignas heterogêneas que surgem de células muito diversificadas do sistema imunológico, tendo origem no linfócito B. Acomete principalmente crianças. Relato de Caso: paciente masculino, com cinco anos de indade, caucasiano, apresentou-se com aumento de volume em hemiface esquerda com trinta dias de evolução, indolor de crescimento rápido. Não foram notadas alterações dentárias. Observou-se abaulamento em hemiface esquerda. A tomografia computadorizada mostrou uma lesão destrutiva de aspecto sólido, acometendo a porção alveolar da mandíbula bilateralmente e as paredes de ambos os seios maxilares, invadindo os antros. A análise cromossômica mostrou o linfoma de Burkitt. O tratamento foi quimioterápico, observando-se redução da lesão após a vigésima sessão. O paciente permanece sem sinal de doença, decorridos cinco anos do início do tratamento. Discussão: esse tipo de linfoma é de crescimento rápido, etiologia incerta, mas com provável envolvimento do vírus Epstein-Barr e origem genética. A lesão tem uma predominância em crianças, com ocorrência maior em meninos. Apresenta duas subclasses, a forma endêmica ou africana e a forma não endêmica ou amaericana; alguns autores citam uma terceira subclasse que seria associada com imunodeficiência adquirida. No entanto, todos esses subtipos são idênticos histologicamente, diferenciando-se apenas nas características epidemiológicas e biológicas.

Introduction: burkitt's lymphoma belongs to the group of the Non-Hodgkin's lymphomas. It presents heterogenic malignant conditions that usually stem from highly diversified cells of the immune system, having their origin in B lymphocytes. Case report: a male Caucasian 5-year-old patient presented a painless growth on his left hemiface for 30 days. No dental disorders were found. The extraoral exam showed a lump in his left hemiface. The computed tomography showed a solid-looking destructive lesion in the alveolar region of the mandible (bilaterally), left mandibular ramus, maxilla (bilaterally), and the walls of both maxillary sinuses, reaching the antra. The Burktt's lymphoma diagnosis was confirmed through the chromosome analysis. The treatment consisted of 20 sessions of chemotherapy, with tumor reduction. The patient remains disease-free after 5 years from the begining of the treatment. Discussion: this kind of lymphoma is a fast-growing tumor whose etiology is uncertain, but which may have association with the Epstein-Barr virus, and/or with genetic conditions. It is a childhood tumor afflicting mainly the boys. It has 2 subclasses, the endemic (or African) form, and the non-endemic (or American) one. Some authors claim that there is a third subclass which would be associated to acquired immunodeficiency. Despite that, all subtypes present identical histology with different epidemiologic and biologic features.