Mitotane Associated With Cisplatin, Etoposide, and Doxorubicin in Advanced Childhood Adrenocortical Carcinoma
| Autor: | Sima Ferman, Maria Helena Andrade Santana, Brás H Oliveira, Leniza C.L. Lichtvan, Patrícia Zancanella, Luiz G Callefe, Mara Albonei Dudeque Pianovski, Sérvio Túlio Stinghen, Suely Z Voss, Bonald C. Figueiredo, Gislaine C Piovezan, Guilherme A Parise |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Oncology medicine.medical_specialty Time Factors Administration Oral Drug Administration Schedule Internal medicine Antineoplastic Combined Chemotherapy Protocols Adrenocortical Carcinoma Humans Medicine Adrenocortical carcinoma Doxorubicin Mitotane Prospective Studies Child Prospective cohort study Survival rate Etoposide Neoplasm Staging Cisplatin Dose-Response Relationship Drug business.industry Remission Induction Hematology medicine.disease Adrenal Cortex Neoplasms Survival Rate Treatment Outcome Child Preschool Pediatrics Perinatology and Child Health Disease Progression Drug Therapy Combination Female Drug Monitoring business Adrenocortical cancer Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Pediatric Hematology/Oncology. 28:513-524 |
| ISSN: | 1077-4114 |
| DOI: | 10.1097/01.mph.0000212965.52759.1c |
| Popis: | 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).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.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.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. |
| Databáze: | OpenAIRE |
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