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1.
Med Pediatr Oncol ; 37(1): 30-5, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11466720

RESUMO

BACKGROUND: Fewer than 10% of Ewing family of tumors (EFT) arise in the vertebrae. Little information is available regarding the clinical presentation and outcome of these tumors. PROCEDURE: We reviewed the clinical features, prognostic factors, and outcome of EFT of the spine identified at our institution between 1962 and 1999. RESULTS: Thirty-three (10%) of 344 patients with EFT had a primary vertebral tumor. There were 21 (64%) males. Median age at diagnosis was 13.3 years. Six patients had metastatic disease and 10 had tumors > or = 8 cm in diameter. Primary sites were sacral (13), thoracic (10), lumbar (8), and cervical (2) vertebrae. We found no association between the affected spinal region and outcome, although sacral tumors were associated with delayed diagnosis (4 vs. 2 months after onset of symptoms, P = 0.076). Pain (n = 32) and neurologic deficits (n = 31; 82% motor, 58% sensory, 42% bladder, 27% bowel) were the most common presenting features. All patients received combination chemotherapy and local radiotherapy. With a median follow up of 9.7 years, 5-year survival and event-free survival ( +/- SD) estimates were 48.1% (8.9%) and 35.6% (8.6%), respectively, comparable to those of other patients with EFT. Outcome was better for patients with tumor size < 8 cm (P = 0.008) or localized disease (P = 0.084). Treatment era and specific tumor site did not affect outcome. CONCLUSIONS: Outcomes are similar for primary EFT of the spine and primary EFT in other sites. Unlike others, we found that patients with sacral tumors did not fare worse than patients with tumors at other spinal sites.


Assuntos
Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Criança , Pré-Escolar , Diagnóstico Diferencial , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Sarcoma de Ewing/secundário , Neoplasias da Coluna Vertebral/secundário , Resultado do Tratamento
2.
Med Pediatr Oncol ; 36(6): 605-11, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11344491

RESUMO

BACKGROUND: Preclinical studies suggest a role of insulin-like growth factor-1 (IGF-1) in the proliferation of osteosarcoma cells in vivo. The purpose of this study is to address the relationship between serum levels of IGF-1 and its binding protein (IGFBP-3), and the clinical behavior and outcome of osteosarcoma in children, and to compare those levels present in osteosarcoma patients with a normal population. PROCEDURE: Serum IGF-1 and IGFBP-3 levels were determined by ELISA in 37 patients with osteosarcoma treated on the same treatment regimen (OS-91 protocol), and who had available serum samples from diagnosis. IGF-1 and IGFBP-3 levels were compared with those previously established in the normal population, matched for age and gender, and were correlated with the presence of metastatic disease, histologic response to preoperative chemotherapy, and event-free survival. RESULTS: In osteosarcoma patients the median IGF-1 level was 275 ng/ml (range, 105-613) and the median IGFBP-3 level was 3.4 mg/L (range, 2.3-5.1). IGF-1 levels differed from those in the normal population (P = 0.029); although we anticipated higher IGF-1 levels than normal children, 68% of observed standardized scores were less than 0. Furthermore, IGF-1 or IGFBP-3 levels failed to correlate with the presence of metastatic disease (P = 0.12 and P = 0.12, respectively), histologic response (Rosen-Huvos grades 3/4 vs. grades 1/2) (P = 0.95 and P = 0.71, respectively), or event-free survival (P = 0.52 and P = 0.41, respectively). There was a strong association observed between IGF-1 and IGFBP-3 levels (P < 0.001). CONCLUSIONS: In this retrospective study of 37 patients, we found that circulating levels of IGF-1 and IGFBP-3 are not predictive of the development or clinical characteristics of pediatric osteosarcoma. However, further studies on a larger patient population should be performed in order to investigate this relationship.


Assuntos
Neoplasias Ósseas/diagnóstico , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Osteossarcoma/diagnóstico , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/sangue , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Metástase Neoplásica , Osteossarcoma/sangue , Osteossarcoma/patologia , Estudos Retrospectivos , Resultado do Tratamento
3.
Cancer Chemother Pharmacol ; 47(3): 211-21, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11320664

RESUMO

PURPOSE: To develop a highly reproducible model of disseminated childhood neuroblastoma in mice to allow secondary evaluation of therapeutics against microscopic disseminated disease. METHODS: CB17/Icr SCID were injected i.v. with 10(3) to 5 x 10(6) human NB-1691 neuroblastoma cells. NB-1691 cells were detected by PCR for synaptophysin and tyrosine hydroxylase in peripheral blood, and bone marrow. Therapeutic studies evaluated topotecan and vincristine as single agents or in combination. Topotecan was administered i.v. daily for 5 days on two consecutive weeks. Courses were repeated every 21 days for three cycles. Vincristine (1 mg/kg) was administered i.v. every 7 days for nine consecutive weeks. Treatment started 11-21 days after tumor cell inoculation. RESULTS: Following injection of > or = 1 x 10(5) cells 100% of mice developed disease. Mice inoculated with 10(7) cells survived a median of 42 days. Survival time was a linear function of the cell inoculum. At autopsy, gross tumor was routinely detected in many organs in particular liver, ovaries, kidneys and adrenals. NB-1691 cells were detected by PCR in peripheral blood, and bone marrow. Immunohistochemical staining showed that lesions were strongly positive for synaptophysin, chromogranin A and negative for leukocyte common antigen. Topotecan (0.6 mg/kg) alone extended median survival from 44 days (controls) to 95 days. When treatment was started 21 days after inoculation of NB-1691 cells, topotecan extended median survival from 39 days (controls) to 91 and 99 days at dose levels of 0.3 and 0.6 mg/kg, respectively. Vincristine (1 mg/kg) extended survival by a median of 9.5 days. In combination with vincristine (1 mg/kg), median survival was increased to 141 days (topotecan 0.6 mg/kg) and 159 days (topotecan 1.0 mg/kg). CONCLUSION: This model of disseminated neuroblastoma is highly reproducible. As this model may more closely simulate childhood disease it may be a valuable adjunct in developing new approaches to advanced stage, poor prognosis neuroblastoma.


Assuntos
Modelos Animais de Doenças , Neuroblastoma , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camundongos , Camundongos SCID , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Topotecan/uso terapêutico , Células Tumorais Cultivadas , Vincristina/uso terapêutico
4.
J Pediatr Hematol Oncol ; 23(2): 93-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11216713

RESUMO

PURPOSE: The benefit of whole-lung irradiation (WLI) for patients who have pulmonary metastases (PM) of Ewing sarcoma family tumors (ESFT) is unclear. At our institution, WLI is reserved for patients with PM that do not respond completely to induction chemotherapy. We reviewed our experience to assess the impact of WLI on clinical outcome. PATIENTS AND METHODS: Twenty-eight patients with ESFT and PM were treated in three consecutive institutional trials (1979-1996). Extent of pulmonary involvement at diagnosis, response of PM after induction chemotherapy, local treatment of PM thereafter, and clinical outcome were recorded. Treatment included primary tumor surgery and/or radiotherapy and 42 to 58 weeks of multiagent chemotherapy. RESULTS: Only eight patients (29%) received WLI. For the entire study group, the estimated 5-year event-free survival was 22.9% +/- 9.0%; the 5-year survival was 37.3% +/- 9.8%. Complete resolution of PM after induction chemotherapy was not correlated with survival (P = 0.53), nor was treatment with WLI (P = 0.87). CONCLUSIONS: The comparable survival of patients with poor and good response of PM to induction chemotherapy suggests that WLI may benefit poor responders. The use of WLI in good responders may provide similar benefit and merits further study.


Assuntos
Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Radioterapia/métodos , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/secundário , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Tábuas de Vida , Neoplasias Pulmonares/mortalidade , Masculino , Pneumonite por Radiação/etiologia , Radioterapia/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem
5.
J Pediatr Hematol Oncol ; 23(2): 99-104, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11216714

RESUMO

PURPOSE: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT). MATERIALS AND METHODS: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures. RESULTS: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow. CONCLUSIONS: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow-up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/diagnóstico , Proteínas de Fusão Oncogênica/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rabdomiossarcoma Alveolar/diagnóstico , Sarcoma de Ewing/diagnóstico , Sarcoma de Células Pequenas/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Medula Óssea/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Criança , Cromossomos Humanos/genética , Diagnóstico Diferencial , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasia Residual , Proteína Proto-Oncogênica c-fli-1 , Proteína EWS de Ligação a RNA , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/patologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Sarcoma de Células Pequenas/genética , Sarcoma de Células Pequenas/patologia , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Fatores de Transcrição/genética , Translocação Genética
6.
J Clin Oncol ; 19(1): 171-82, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11134210

RESUMO

PURPOSE: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. RESULTS: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P: = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. CONCLUSION: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Humanos , Ifosfamida/administração & dosagem , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Projetos Piloto , Taxa de Sobrevida
7.
J Pediatr Hematol Oncol ; 23(9): 568-71, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11902298

RESUMO

PURPOSE: To determine the incidence, timing, and clinical significance of long-bone fractures in children with Ewing sarcoma family of tumors (ESFT). PATIENTS AND METHODS: We retrospectively reviewed 93 consecutive cases of ESFT of the long bones seen at a single institution over the course of a 37-year period. RESULTS: Fracture occurred in 14 (15%) of 93 patients with long-bone ESFT, most commonly in the femur. Approximately 30% of patients with tumors of the femur had fractures at some point in the course of their disease. The incidence of fracture was highest among patients with tumors of the proximal third of the femur (50%); these fractures were usually present at the time of initial diagnosis. Nine (64%) of the 14 fractures occurred after the start of radiotherapy, and three of these were associated with either local recurrence or second malignancy. CONCLUSIONS: Patients with femoral ESFT are at high-risk for fracture. If fractures occur after the completion of therapy, recurrence or second malignancy should be suspected.


Assuntos
Neoplasias Ósseas/complicações , Fraturas Espontâneas/etiologia , Sarcoma de Ewing/complicações , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/etiologia , Fraturas Espontâneas/epidemiologia , Histiocitoma Fibroso Benigno/complicações , Humanos , Masculino , Recidiva Local de Neoplasia/complicações , Segunda Neoplasia Primária/complicações , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/radioterapia , Tíbia , Fatores de Tempo , Resultado do Tratamento , Suporte de Carga
8.
Clin Cancer Res ; 6(10): 4110-8, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11051264

RESUMO

The activity of temozolomide combined with irinotecan (CPT-11) was evaluated against eight independent xenografts (four neuroblastomas, three rhabdomyosarcomas, and one glioblastoma). In all studies, temozolomide was administered p.o. daily for 5 consecutive days/cycle, found in preliminary studies to be the optimal schedule for administration. Irinotecan was administered i.v. for 5 days for 2 consecutive weeks/cycle. Treatment cycles were repeated every 21 days for a total of three cycles over 8 weeks. In combination, temozolomide and CPT-11 induced complete responses in four neuroblastomas, two rhabdomyosarcomas, and the glioblastoma line. The activity of the combination was significantly greater than the activity of either agent administered alone in four tumor lines. Of interest, the interaction appeared independent of tumor MGMT or mismatch repair phenotype, suggesting that the mechanism of synergy may be independent of O6-methylation by temozolomide. Pharmacokinetic studies indicated no detectable interaction between these two agents. Further, coadministration of CPT-11 appeared to reduce the toxicity of temozolomide in tumor-bearing mice.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Pareamento Incorreto de Bases , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Reparo do DNA , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Administração Oral , Alquilantes/farmacocinética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Camptotecina/farmacocinética , Dacarbazina/farmacocinética , Feminino , Glioblastoma/tratamento farmacológico , Irinotecano , Camundongos , Camundongos Endogâmicos CBA , Transplante de Neoplasias , Neuroblastoma/tratamento farmacológico , Fenótipo , Rabdomiossarcoma/tratamento farmacológico , Temozolomida , Fatores de Tempo
9.
J Pediatr Hematol Oncol ; 22(4): 321-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10959902

RESUMO

PURPOSE: Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies. PATIENTS AND METHODS: The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment. RESULTS: Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the EW87 group. CONCLUSION: Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.


Assuntos
Anemia Macrocítica/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/sangue , Leucemia Mieloide/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Sarcoma de Ewing/sangue , Trombocitopenia/induzido quimicamente , Adolescente , Adulto , Anemia Macrocítica/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Índices de Eritrócitos/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide/sangue , Masculino , Síndromes Mielodisplásicas/induzido quimicamente , Segunda Neoplasia Primária/sangue , Contagem de Plaquetas/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Trombocitopenia/sangue
10.
Med Pediatr Oncol ; 35(2): 96-103, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10918230

RESUMO

BACKGROUND: The p53 tumor suppressor gene is the most commonly mutated gene in human cancer, and mutations arise in a wide variety of tumor types. Wild-type p53 functions as a regulator of apoptosis, so mutations in the p53 gene are generally associated with aggressive tumors and a poor prognosis. PROCEDURE: We have investigated the p53 mutation and MDM2 amplification frequencies in biopsies from pediatric rhabdomyosarcoma (RMS) tumors and cell lines by SSCP and Southern analyses. RESULTS: A mutation was detected in only 1 of 20 tumor specimens (5%), whereas the frequency in established RMS cell lines was significantly higher (6/10, 60%). p53 Mutations were more common in cell lines derived from tumors previously exposed to chemotherapy compared to those derived from tumors at di-agnosis, and it is likely that these mutations enhanced the probability of successful long-term culture. The frequency of MDM2 gene amplification in patient biopsies was also low (2/20, 10%). Interestingly, complete responses to treatment were obtained in the two patients with tumors that demonstrated amplification of MDM2. The response to treatment of patients with tumors wild-type for p53 and without MDM2 amplification was quite varied, indicating that expression of a wild-type p53 gene at diagnosis cannot always facilitate a favorable outcome. CONCLUSIONS: p53 mutation and MDM2 gene amplification frequencies are extremely low in RMS tumors, but a wild-type p53 genotype is not always associated with a favorable prognosis.


Assuntos
Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogênicas/genética , Rabdomiossarcoma/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Southern Blotting , Linhagem Celular , Criança , Pré-Escolar , Terapia Combinada , Éxons , Amplificação de Genes , Humanos , Lactente , Mutação , Polimorfismo Conformacional de Fita Simples , Prognóstico , Proteínas Proto-Oncogênicas c-mdm2 , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/patologia
11.
J Pediatr Surg ; 35(6): 948-53; discussion 953-4, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10873042

RESUMO

PURPOSE: The associations between age at diagnosis, tumor characteristics, and outcome in children diagnosed with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) were studied. METHODS: Retrospective review was conducted of 192 children from 1962 through 1996. Patients were divided into groups: birth to 1 year (n = 13), 1 to 5 years (n = 26), 5 to 10 years (n = 49), 10 to 15 years (n = 55), and older than 15 years (n = 49) of age at diagnosis. Characteristics including IRS group, histological grade and pattern, tumor size, and invasiveness were investigated. Survival rate was estimated by age group. The median follow-up was 8.8 years (range, 2 to 28 years). RESULTS: There were 81 group I patients, 40 group II, 41 group III, and 30 group IV. A significant difference of IRS groups among the age groups was seen (P = .034). There were no IRS group IV patients less than 1 year of age; 50% of IRS group IV patients were older than 15 years. A significant difference in the distribution of histological grade among the age groups (P = .032) was seen. Ten of 13 (77%) children less than 1 year of age had low-grade tumors, whereas 42%, 45%, 60%, and 37% of patients aged 1 to 5, 5 to 10, 10 to 15, and older than 15 years, respectively, had low-grade tumors. Patients older than 15 years had the highest incidence of invasive tumors (59%). Histological pattern also varied with age. The most prevalent histology in the less-than-1-year age group was infantile fibrosarcoma. No predominant histology was seen in the 1- to 5-year age group. Malignant fibrous histiocytoma was the most frequent histological subtype in children between 5 and 10 years of age. In the 10- to 15-year age group and children older than 15 years the malignant peripheral nerve sheath tumor and synovial sarcoma were the most prevalent subtypes. Without adjusting for any other factors, age group was prognostic of survival (P = .007). Patients less than 1 year at diagnosis had the best outcome, with a 5-year survival rate of 92% +/- 9%. Five-year estimates were lowest for patients older than 15 years (49% +/- 7%). CONCLUSIONS: Significant differences in IRS group, histological grade, and histological subtype were observed in different age groups. Infants with NRSTS were more likely to have low grade, less invasive, and lower stage tumors. These characteristics may account for their improved prognosis.


Assuntos
Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Fibrossarcoma/diagnóstico , Histiocitoma Fibroso Benigno/diagnóstico , Humanos , Lactente , Masculino , Neoplasias de Bainha Neural/diagnóstico , Prognóstico , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma Alveolar de Partes Moles/diagnóstico , Sarcoma Sinovial/diagnóstico , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida
12.
Cancer ; 88(9): 2172-80, 2000 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-10813731

RESUMO

BACKGROUND: Bone sarcomas of the head and neck are difficult to resect. The authors reviewed their institutional experience with these tumors to characterize patients' clinical findings and to assess the impact of surgical resection on outcome. METHODS: The records of the 28 patients with bone sarcomas originating in the head and neck treated at St. Jude Children's Research Hospital between March 1962 and January 1998 were reviewed. RESULTS: There were 10 males and 18 females (median age, 12.6 years) each with a single sarcoma: osteosarcoma (18), Ewing sarcoma (7), malignant fibrous histiocytoma (MFH) (2), and fibrosarcoma (1). Primary tumor sites included the maxilla (13), skull (10), mandible (2), and other sites (3). All but one patient with Ewing sarcoma had localized disease at the time of diagnosis. All patients underwent surgery: complete resection, 8; gross total resection, 4; incomplete resection, 14; and biopsy only, 2; 22 also received chemotherapy. Radiotherapy was given to all patients with Ewing sarcoma and to four patients with primary osteosarcoma. Twelve patients survived a median of 8.4 years after diagnosis, 14 died of disease, and 2 died of unrelated causes. Local disease progression was evident in 12 patients (9 with osteosarcoma, 2 with MFH, and 1 with Ewing sarcoma) who died of disease, 9 of whom had the initial treatment of biopsy alone or incomplete resection. Patients with osteosarcoma who had the initial treatment of incomplete resection or biopsy alone were more likely to experience local failure (P = 0.001) and had poorer survival (P = 0.014) than those who underwent complete or gross total resection. CONCLUSIONS: Bone sarcomas of the head and neck are rare among children and most often are localized at the time of diagnosis. Incomplete resection of osteosarcoma is associated with local failure and poor outcome. Although aggressive surgery is essential for the cure of osteosarcoma, its necessity in the treatment of Ewing sarcomas remains controversial.


Assuntos
Sarcoma/cirurgia , Neoplasias Cranianas/cirurgia , Adolescente , Adulto , Causas de Morte , Quimioterapia Adjuvante , Criança , Pré-Escolar , Progressão da Doença , Feminino , Fibrossarcoma/cirurgia , Histiocitoma Fibroso Benigno/cirurgia , Hospitais Pediátricos , Humanos , Lactente , Masculino , Neoplasias Mandibulares/cirurgia , Neoplasias Maxilares/cirurgia , Recidiva Local de Neoplasia/patologia , Osteossarcoma/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Sarcoma de Ewing/cirurgia , Taxa de Sobrevida , Tennessee , Resultado do Tratamento
13.
J Pediatr Hematol Oncol ; 22(2): 112-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10779023

RESUMO

PURPOSE: The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital. METHODS: The authors reviewed the records of 199 patients receiving ICR at St. Jude between June 1986 and December 31, 1994 for evidence of RTT. Their median age was 13.3 years (range 1.2-24.8); 150 patients were white and 112 were male patients. Diagnoses included osteosarcoma (n = 82), Ewing sarcoma (n = 82), rhabdomyosarcoma (n = 28), and a group of other tumors (n = 7). RESULTS: The authors estimated the proportion of patients with severe RTT during the first five cycles of ICR and within 1 year after therapy for three groups of patients receiving ifosfamide (IFOS, n = 110), ifosfamide/cisplatin (IFOS/CDDP, n = 51), and ifosfamide/carboplatin (IFOS/CARBO, n = 38). The IFOS/CDDP patients received three cycles of IFOS before receiving CDDP and received only 200 mg/m2 by cycle 5, whereas the IFOS/CARBO patients received both agents simultaneously. The authors compared the probability of severe RTT among treatment groups using a generalized linear model for the first five cycles of ICR, as well as the probability of severe RTT within 1 year after therapy among treatment groups for patients receiving all prescribed IFOS using an exact chi-square test with pairwise comparisons when the three-way P value was less than 0.10. The proportion of patients with severe RTT during the first three cycles of ICR was significantly greater in the IFOS/CARBO group than in the other two. Although the proportion of patients with severe RTT in the IFOS/CDDP group increased during cycles 4/5, the proportion of patients with severe RTT remained significantly greater in the IFOS/ CARBO group. Within 1 year after therapy, the proportion of patients with severe RTT differed among the three groups, and pairwise comparisons revealed a significant difference between the IFOS and the IFOS/CDDP group. Severe RTT developed in four IFOS/CDDP patients more than 1 year after therapy, suggesting a long-term effect of CDDP on tubular function. CONCLUSIONS: Chemotherapy regimens including IFOS/ CARBO produce severe acute RTT more frequently than regimens including IFOS or IFOS/CDDP. Patients receiving IFOS/ CDDP appear at risk for delayed RTT. Long-term follow-up of these patients is essential to assess whether the number of patients receiving IFOS/CDDP with severe RTT continues to increase over time and to evaluate the long-term significance of these abnormalities.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Ifosfamida/efeitos adversos , Túbulos Renais/efeitos dos fármacos , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Ifosfamida/uso terapêutico , Lactente , Masculino , Osteossarcoma/tratamento farmacológico , Estudos Retrospectivos , Rabdomiossarcoma/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico
14.
Clin Cancer Res ; 6(3): 998-1007, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10741727

RESUMO

The antitumor activity of the methylating agent temozolomide has been evaluated against a panel of 17 xenografts derived from pediatric solid tumors. Temozolomide was administered p.o. daily for five consecutive days at a dose level of 66 mg/kg. Courses of treatment were repeated every 21 days for three cycles. Tumor lines were classified as having high, intermediate, or low sensitivity, determined by complete responses, partial responses, or stable disease, respectively. Overall, temozolomide induced complete responses in five lines and partial responses in three additional tumor lines, giving objective regressions in 47% of xenograft lines. Analysis of temozolomide plasma systemic exposure indicated that this dose level was relevant to exposure achieved in patients. Tumors were analyzed by immunoblotting for levels of O6-methylguanine-DNA methyltransferase (MGMT) and two mismatch repair proteins, MLH-1 and MSH-2. Tumors classified as having high or intermediate sensitivity had low or undetectable MGMT and expressed detectable MLH-1 and MSH-2 proteins. Tumors classified as having low sensitivity had either (a) high MGMT or (b) low or undetectable MGMT but were deficient in MLH-1. The relationship between p53 and response to temozolomide was also examined. In vitro temozolomide did not induce p21cip1 in p53-competent NB-1643 neuroblastoma cells. Suppression of p53 function in NB1643 clones through stable expression of a trans dominant negative p53 (NB1643p53TDN) did not confer temozolomide resistance. Similarly, tumor sensitivity to temozolomide did not segregate with p53 genotype or p53 functional status. These results indicate that MGMT is the primary mechanism for temozolomide resistance, but in the absence of MGMT, proficient mismatch repair determines sensitivity to this agent.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Proteínas de Ligação a DNA , Dacarbazina/análogos & derivados , Neoplasias Experimentais/prevenção & controle , Proteínas Adaptadoras de Transdução de Sinal , Animais , Antineoplásicos Alquilantes/farmacocinética , Pareamento Incorreto de Bases , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/prevenção & controle , Proteínas de Transporte , Divisão Celular/efeitos dos fármacos , Criança , Reparo do DNA , Dacarbazina/sangue , Dacarbazina/farmacocinética , Dacarbazina/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Endogâmicos CBA , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neuroblastoma/patologia , Neuroblastoma/prevenção & controle , Proteínas Nucleares , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Fenótipo , Proteínas Proto-Oncogênicas/metabolismo , Rabdomiossarcoma/patologia , Rabdomiossarcoma/prevenção & controle , Temozolomida , Transplante Heterólogo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/fisiologia
15.
Cancer ; 88(1): 198-204, 2000 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-10618624

RESUMO

BACKGROUND: Hemangiopericytoma (HPC) is a soft-tissue neoplasm most commonly seen in adults; only 5-10% of cases occur in children. Childhood HPC comprises two distinct clinical entities. In children older than 1 year, it behaves in a manner similar to adult HPC. Infantile HPC, however, although histologically identical to adult HPC, has a more benign clinical course. The reasons for these differences in the natural history of HPC are not well understood. METHODS: The authors reviewed the clinicopathologic features of HPC as well as the treatment and outcomes of the 12 children (9 males and 3 females) treated for this disease at St. Jude Children's Research Hospital over a 35-year period. RESULTS: At diagnosis, 9 patients were older than 1 year and 3 were younger than 1 year. Among the 9 older patients, tumors were most commonly found in the lower extremities (n = 5). One patient had been treated for acute lymphoblastic leukemia 15 years earlier. One patient had metastatic disease at diagnosis, and three had unresectable tumors. Two patients experienced objective responses to chemotherapy. Three patients died of disease progression. Among the three infants, two had unresectable disease at diagnosis, and both experienced excellent responses to neoadjuvant chemotherapy. In one case, the response of the tumor to chemotherapy correlated with maturation to hemangioma. All three infants are alive without evidence of disease. CONCLUSIONS: HPC in children older than 1 year does not differ from adult HPC, and aggressive multimodality therapy is required. Infantile HPC, on the other hand, is characterized by better clinical behavior, with documented chemoresponsiveness and spontaneous regression, and requires a more conservative surgical approach. In some cases of infantile HPC, this benign behavior correlates with maturation to hemangioma.


Assuntos
Hemangiopericitoma , Criança , Pré-Escolar , Terapia Combinada , Feminino , Hemangiopericitoma/patologia , Hemangiopericitoma/terapia , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Prontuários Médicos , Estadiamento de Neoplasias , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento
16.
Clin Cancer Res ; 5(11): 3617-31, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10589779

RESUMO

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v. bolus on a schedule found previously to be optimal. Drug was administered daily for 5 days on 2 consecutive weeks with cycles repeated every 21 days over a period of 8 weeks. Doses of topotecan ranged from 0.16 to 1.5 mg/kg to simulate clinically achievable topotecan lactone plasma systemic exposures. Vincristine was administered i.v. every 7 days at a fixed dose of 1 mg/kg. Given as a single agent, vincristine induced complete responses (CRs) in all mice bearing two rhabdomyosarcomas (Rh28 and Rh30) and some CRs in Rh12-bearing mice (57%) but relatively few CRs (<29%) in other tumors. As a single agent, topotecan induced CR in a low proportion of tumor lines. A dose-response model with a logit link function was used to investigate whether the combination of topotecan and vincristine resulted in greater than expected responses compared with the activity of the agents when administered alone. Only CR was used to evaluate tumor responses. The combination resulted in significantly greater than expected CRs than individual agents in nine tumor lines (four neuroblastoma, three brain tumors, and two rhabdomyosarcomas). Similar event-free (failure) distributions were shown in SJ-GBM2 glioblastoma xenografts, whether vincristine was administered on day 1 or day 5 of each topotecan course. To determine whether the increased antitumor activity with the combination was attributable to a change in drug disposition, extensive pharmacokinetic studies were performed. However, little or no interaction between these two agents was determined. Toxicity of the combination was marked by prolonged thrombocytopenia and decreased hemoglobin. However, approximately 75 and 80% of the maximum tolerated dose of each single agent, topotecan (1.5 mg/kg) or vincristine (1 mg/kg), could be given in combination, resulting in a combination toxicity index of approximately 1.5. These results show that the therapeutic effect of combining topotecan with vincristine was greater than additive in most tumor models of childhood solid tumors, and toxicity data suggest that this can be administered to mice with only moderate reduction in the dose levels for each agent.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Cerebelares/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Rabdomiossarcoma/tratamento farmacológico , Topotecan/uso terapêutico , Vincristina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Encefálicas/patologia , Neoplasias Cerebelares/patologia , Criança , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Meduloblastoma/tratamento farmacológico , Meduloblastoma/patologia , Camundongos , Camundongos Endogâmicos CBA , Neuroblastoma/patologia , Rabdomiossarcoma/patologia , Timectomia , Topotecan/administração & dosagem , Topotecan/farmacocinética , Transplante Heterólogo , Células Tumorais Cultivadas , Vincristina/administração & dosagem , Vincristina/farmacocinética , Irradiação Corporal Total
17.
J Clin Oncol ; 17(6): 1815-24, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10561220

RESUMO

PURPOSE: In a preclinical model of neuroblastoma, administration of irinotecan daily 5 days per week for 2 consecutive weeks ([qd x 5] x 2) resulted in greater antitumor activity than did a single 5-day course with the same total dose. We evaluated this protracted schedule in children. PATIENTS AND METHODS: Twenty-three children with refractory solid tumors were enrolled onto a phase I study. Cohorts received irinotecan by 1-hour intravenous infusion at 20, 24, or 29 mg/m(2) (qd x 5) x 2 every 21 days. RESULTS: The 23 children (median age, 14.1 years; median prior regimens, two) received 84 courses. Predominant diagnoses were neuroblastoma (n = 5), osteosarcoma (n = 5), and rhabdomyosarcoma (n = 4). The dose-limiting toxicity was grade 3/4 diarrhea and/or abdominal cramps in six of 12 patients treated at 24 mg/m(2), despite aggressive use of loperamide. The maximum-tolerated dose (MTD) on this schedule was 20 mg/m(2)/d. Five patients had partial responses and 16 had disease stabilization. On day 1, the median systemic exposure to SN-38 (the active metabolite of irinotecan) at the MTD was 106 ng-h/mL (range, 41 to 421 ng-h/mL). CONCLUSION: This protracted schedule is well tolerated in children. The absence of significant myelosuppression and encouraging clinical responses suggest compellingly that irinotecan be further evaluated in children using the (qd x 5) x 2 schedule, beginning at a dose of 20 mg/m(2). These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Ensaio de Cápsula Sub-Renal , Adolescente , Adulto , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Irinotecano , Masculino , Camundongos , Resultado do Tratamento
18.
J Clin Oncol ; 17(12): 3697-705, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10577841

RESUMO

PURPOSE: The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution. PATIENTS AND METHODS: We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996. Demographic data, tumor characteristics, treatment, and outcomes were recorded. Univariate and multivariate analyses of prognostic factors for survival, event-free survival (EFS), and local and distant recurrence were performed. RESULTS: At a median follow-up of 9.2 years, 5-year survival and EFS rates for the entire cohort were 89% +/- 3% and 77% +/- 4%, respectively. In univariate models, positive surgical margins (P =.004), tumor size > or = 5 cm (P <.001), invasivene (P =.002), high grade (P =.028), and intra-abdominal primary tumor site (P =.055) adversely affected EFS. All of these factors except invasiveness remained prognostic of EFS and survival in multivariate models. Positive surgical margins (P =.003), intra-abdominal primary tumor site (P =.028), and the omission of radiation therapy (P =.043) predicted local recurrence, whereas tumor size > or = 5 cm (P <.001), invasiveness (P <.001), and high grade (P =.004) predicted distant recurrence. CONCLUSION: In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.


Assuntos
Sarcoma/diagnóstico , Adolescente , Adulto , Quimioterapia Adjuvante , Criança , Pré-Escolar , Intervalo Livre de Doença , Seguimentos , Humanos , Lactente , Recidiva Local de Neoplasia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcoma/tratamento farmacológico , Sarcoma/mortalidade , Sarcoma/cirurgia , Resultado do Tratamento
19.
J Pediatr Hematol Oncol ; 21(5): 370-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10524449

RESUMO

PURPOSE: Although brain metastases rarely occur in children with solid tumors, pediatric Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are among those most likely to metastasize to the brain. The authors review their institution's experience of brain metastases of ES and RMS. PATIENTS AND METHODS: The clinical characteristics, therapy, and outcome of all patients treated at St. Jude Children's Research Hospital over a 36-year period who had ES or RMS with brain metastases were reviewed. RESULTS: Of 419 patients with RMS, 10 (2.4%) had brain metastases. Of 335 patients with ES, 11 (3.3%) had brain metastases. The median age of the 21 patients was 10.4 years (range, 0.4-18.0 years) at the time of primary diagnosis. All had clinical signs of central nervous system (CNS) involvement. Outcome was dismal: The median duration of survival after diagnosis of brain metastasis was 2.7 months. The estimated survival 1 year after detection of brain involvement was 23.8%+/-8.5% (mean +/- standard error). One patient, who underwent chemotherapy, surgical resection, and radiotherapy, at the time of this writing is a long-term survivor. CONCLUSIONS: Brain metastases are rare in children with ES and RMS, but carry a grave prognosis. Because most brain metastases are accompanied by signs of neurologic involvement, routine imaging studies of asymptomatic children are not necessary. Combined-modality treatment offers the best chance of long-term survival.


Assuntos
Neoplasias Ósseas/terapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Rabdomiossarcoma/secundário , Sarcoma de Ewing/secundário , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/terapia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Análise de Sobrevida , Tennessee , Resultado do Tratamento
20.
J Clin Oncol ; 17(1): 180-90, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10458232

RESUMO

PURPOSE: To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors. PATIENTS AND METHODS: From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance. RESULTS: Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white. Nineteen patients presented with metastatic disease, 29 had tumors greater than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and time to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72%+/-8% and 60%+/-9%, respectively. CONCLUSION: Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact on disease-free survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma de Ewing/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Masculino , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/mortalidade , Prognóstico , Sarcoma de Ewing/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Taxa de Sobrevida
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