RESUMO
We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27 weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study suggests the possible application of O-TIE treatment in a neoadjuvant setting during pregnancy and recommends a schedule that can be considered for the treatment of patients with high-risk sarcomas who cannot be treated with intensive chemotherapy for various reasons.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Rabdomiossarcoma Alveolar/tratamento farmacológico , Administração Oral , Adolescente , Ciclofosfamida/administração & dosagem , Ciclofosfamida/análogos & derivados , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Feminino , Humanos , Idarubicina/administração & dosagem , Gravidez , PrognósticoRESUMO
BACKGROUND: Carboplatin dosing in children is based on renal function and there exists a wealth of formulae available for calculating the body surface area (BSA), the glomerular filtration rate (GFR), and the carboplatin dose. PATIENTS AND METHODS: A fictitious group of children with different ages and body builds was 'constructed'. For comparison of formulae, bias and precision were assessed. RESULTS: BSA calculations according to DuBois-DuBois, Gehan-George, Mosteller, and Boyd showed good agreement. GFR calculations according to the weight-based Cole formula and the Léger formula gave comparable results. Regarding GFR in young children, the weight-and creatinine-based Cole and the Schwartz formula showed clear differences. Again, carboplatin dose calculations according to Marina, Newell, and Chatelut are comparable. Moreover, the precision of the creatinine measurement has a clear influence on the result of the dose calculation. CONCLUSIONS: The choice of the GFR formula is more important for the carboplatin dose calculation compared to the BSA or dose equation. GFR calculations in children show marked, age-dependent variations. A sequence of multiple calculation steps (especially for the Schwartz and Marina formulae) may lead to considerable uncertainty and proneness to error in the clinical routine. In high-risk patients, GFR should be measured precisely and complemented by therapeutic drug monitoring.
Assuntos
Carboplatina/administração & dosagem , Carboplatina/farmacocinética , Quimioterapia Assistida por Computador/métodos , Rim/metabolismo , Modelos Biológicos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Peso Corporal , Simulação por Computador , Relação Dose-Resposta a Droga , Esquema de Medicação , Taxa de Filtração Glomerular , Humanos , Rim/efeitos dos fármacos , Taxa de Depuração Metabólica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy. METHODS: All patients received 4 courses of cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites. RESULTS: Patients with localized malignant NGGCT (n = 116) demonstrated 5-year progression-free survival (PFS) and overall survival (OS) of 0.72 ± 0.04 and 0.82 ± 0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar, 5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3 patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen were local, 6 combined, and 7 distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n = 33) demonstrated 5-year PFS and OS of 0.68 ± 0.09 and 0.75 ± 0.08, respectively; 1 patient died following progression on treatment and 9 (27%) relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/mL, 19/149 patients, of whom 11 relapsed; P < 0.0003) and residual disease following treatment, including after second-look surgery (n = 52/145 evaluable patients, 26 relapsed; P = 0.0002) as significant prognostic indicators in this cohort. CONCLUSION: In localized malignant NGGCT, craniospinal radiotherapy could be avoided without increased relapses outside the radiotherapy field. Chemotherapy and craniospinal radiotherapy remain the gold standard for metastatic disease.