Assuntos
Infecções por Coronavirus/diagnóstico , Infecção Hospitalar/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Infecções/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Isolamento de Pacientes/métodos , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , TailândiaRESUMO
PURPOSE: The objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] > or = 1,000/mm3 and platelet count > or = 100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 microg/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors. PATIENTS AND METHODS: From June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2 per day x 5), carboplatin (400 mg/m2 per day x 2), and etoposide (100 mg/m2 per day x 5) and randomized to receive either 5.0 microg/kg per day or 10.0 microg/kg per day of G-CSF subcutaneously until recovery of ANC to > or = 1,000/mm3. RESULTS: The incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC > or = 1,000/mm(-3) for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count < or = 20,000/mm3 during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery > or =100,000/mm3 for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%-59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively. CONCLUSION: In summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 microg/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/etiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Lactente , Contagem de Leucócitos , Masculino , Neoplasias/mortalidade , Neutropenia/prevenção & controle , Neutrófilos , Estudos Prospectivos , Grupos Raciais , Proteínas Recombinantes , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Estados UnidosRESUMO
Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor of primitive origin occurring primarily in children and young adults. Based on published reports in the literature, the response to conventional chemotherapy is poor. We report three pediatric patients successfully treated with dose-intensive, multimodal therapy. Between August 1994 and March 1998, we evaluated three consecutive patients with DSRCT at Children's Hospital and Regional Medical Center, Seattle, Washington. We established the diagnosis based on clinical presentation, radiologic staging, and pathologic review with immunohistochemical staining. All patients received a combined modality protocol including dose-intensive chemotherapy (two of them with peripheral blood stem cell [PBSC] support), second look surgery, and consolidative local irradiation. The patients remain in continuous remission at 66, 42, and 26 months after diagnosis, respectively. Two of our patients were younger than any previously reported patient, extending the age group for which DSRCT should be considered on diagnosis of small round cell tumors. The uniform survival achieved in our series indicates potential benefit for the combination of dose-intensive multiagent chemotherapy, local irradiation, and aggressive surgical approach in this disease.
Assuntos
Neoplasias de Tecidos Moles/terapia , Adolescente , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Masculino , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/mortalidadeRESUMO
OBJECTIVE: We sought to establish the outcome and optimal therapeutic sequence for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor of the chest wall. METHODS: Patients 30 years of age or younger with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor of the bone were randomly assigned to receive vincristine, doxorubicin, cyclophosphamide, and dactinomycin or those drugs alternating with ifosfamide and etoposide. Local control was obtained with an operation, radiotherapy, or both. RESULTS: Fifty-three (13.4%) of 393 patients had primary tumors of the chest wall (all rib). Event-free survival at 5 years was 57% for the chest wall compared with 61% for other sites (P >.2). Ifosfamide and etoposide improved outcome in the overall group (5-year event-free survival, 68% vs 54%; P =.002), and a similar trend occurred in chest wall lesions (5-year event-free survival, 64% vs 51%). Patients with chest wall lesions had more attempts at initial surgical resection (30%) than those with other primary tumor sites (8%, P <.01). The attempt at initial resection for chest wall lesions did not correlate with size. Initial resections at other sites were restricted to smaller tumors. Initial resection resulted in negative pathologic margins in 6 of 16 patients, whereas the delayed resection resulted in negative margins in 17 of 24 patients (P =.05). Although there was no difference in survival by timing of the operation in rib lesions, a higher percentage of patients with initial surgical resection received radiation than those with resection after initial chemotherapy (P =. 13). CONCLUSIONS: Although rib primary tumors are significantly larger than tumors found in other sites, their outcome is similar. We favor delayed resection whenever possible to minimize the number of patients requiring radiation therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Costelas , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Criança , Terapia Combinada , Intervalo Livre de Doença , Humanos , Sarcoma de Ewing/mortalidade , Resultado do TratamentoRESUMO
71 children with sarcomas were treated in a prospective pilot study to determine whether granulocyte colony stimulating factor (G-CSF) permits compression of the interval between chemotherapy cycles. Patients had Ewing's sarcoma/primitive neuroectodermal tumour (PNET), rhabdomyosarcoma, non-rhabdo soft tissue sarcomas or other advanced soft tissue tumours. The chemotherapy alternated vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, with G-CSF between courses. Therapy had two phases: induction (six cycles) and continuation (six cycles), which included primary tumour treatment with surgery and/or radiation. Chemotherapy cycles began every 14 days, or upon absolute neutrophil count (ANC) and platelet count recovery. The median chemotherapy cycle interval was 16 (11-48) days in the induction phase, with a median average relative dose intensification (ARDI) of 1.27 compared with every-21-day therapy. In the continuation phase, the median cycle interval was 21 days, with a median ARDI of 1.10. Radiation therapy prolonged chemotherapy intervals, whilst erythropoietin shortened them. Toxicity was modest for such chemotherapy. Event-free survival is comparable with or superior to that in recent large studies. G-CSF permits intensification of this regimen through interval compression. The impact of this approach on efficacy remains to be determined in a randomised trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Sarcoma de Ewing/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Lactente , Masculino , Projetos Piloto , Estudos Prospectivos , Rabdomiossarcoma/tratamento farmacológico , Análise de Sobrevida , Vincristina/administração & dosagemRESUMO
BACKGROUND: To improve the prognosis for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), and undifferentiated sarcoma (UDS), we tested the feasibility of a brief, intensive regimen of chemotherapy that maximizes dose intensity. PROCEDURE: Twenty-four children and adolescents with metastatic sarcomas received VACIME chemotherapy, consisting of eight courses of vincristine 2 mg/m(2) on day 0; doxorubicin 20 mg/m(2)/day on days 0-3; cyclophosphamide 360 mg/m(2)/day on days 0-4; ifosfamide 1,800 mg/m(2)/day on days 0-4; mesna 2,400 mg/m(2)/day; and etoposide 100 mg/m(2)/day on days 0-4. Doxorubicin was omitted in courses 7 and 8. Granulocyte colony-stimulating factor (G-CSF) was used routinely following each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery and resolution of nonhematopoietic toxicities permitted. Surgical resection followed course 6, and radiotherapy followed the completion of all therapy. RESULTS: Thirteen patients achieved a complete response (CR) with chemotherapy alone, and seven more achieved a CR following surgical resection after course 6 (overall CR rate 83%). There was one toxic death. Thirteen patients developed progressive disease, with 2- and 4-year event-free survivals (95% confidence interval) of 50% (30-70%) and 45% (25-65%), respectively. Myelosuppression was severe and cumulative, leading to dose reductions and chemotherapy interval delays. Mucositis was the most common nonhematopoietic toxicity. CONCLUSIONS: VACIME chemotherapy was a feasible dose-intensive regimen for pediatric patients with metastatic sarcomas. Cumulative hematopoietic toxicity and severe mucositis limited the delivery of chemotherapy as prescribed. The CR and 2-year event-free survival rates were superior to those of most previously reported regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriemia/induzido quimicamente , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Lactente , Masculino , Mesna/administração & dosagem , Mesna/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Metástase Neoplásica , Neutropenia/induzido quimicamente , Estudos Prospectivos , Indução de Remissão , Sarcoma/radioterapia , Estomatite/induzido quimicamente , Fatores de Tempo , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Over 50% of patients with newly diagnosed rhabdomyosarcoma (RMS) are in the 'intermediate risk' group with a 3-year progression-free survival of approximately 65%. This group consists of stage 1, group III, non-orbit tumours; stage 2, group II and III; and all stage 3 patients utilising the Intergroup Rhabdomyosarcoma Study (IRS) staging system. The role of doxorubicin in the treatment of RMS has been controversial. Ifosfamide, both alone and in combination with etoposide, has significant activity in patients with RMS. The aim of this pilot study was to examine the efficacy and toxicity of a chemotherapy regimen of alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide for intermediate risk RMS. 30 patients with intermediate risk RMS or undifferentiated sarcoma (US) were treated with alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and etoposide/ifosfamide (EI) at planned intervals of 3 weeks. Local treatment of the tumour in most cases was performed after four cycles of chemotherapy, followed by an additional 10 cycles of chemotherapy. At a median follow-up of 37.5 months, the Kaplan-Meier estimate of 3-year event-free survival was 85% (95% confidence interval 72-99%). The overall survival at 3 years was 91% (95% confidence interval 80-100%). No patient died from toxicity. The most common toxicity was febrile neutropenia in 35% of VDC and 26% of EI cycles. No nephrotoxicity or cardiac toxicity was seen. No patient progressed prior to week 12 local therapy. Alternating cycles of VDC and EI are an effective treatment for patients with intermediate risk RMS and US. Toxicity is tolerable. Delaying local treatment until week 12 does not compromise outcome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rabdomiossarcoma/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Estudos de Viabilidade , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Ifosfamida/administração & dosagem , Lactente , Recém-Nascido , Neoplasias Meníngeas/tratamento farmacológico , Projetos Piloto , Fatores de Risco , Neoplasias Urogenitais/tratamento farmacológico , Vincristina/administração & dosagemRESUMO
This prospective cohort study determined the incidence and risk factors for development of postdural puncture headache (PDPH) in children after lumbar puncture (LP). Eighty-six children were enrolled. LPs were performed with use of 22-gauge spinal needles with the bevel oriented parallel to the long axis of the spine. Follow-up telephone interviews and patients' diary of symptoms were collected. Headache brought on by sitting up and relieved by lying down was defined as PDPH. Of the 80 who completed the study, six (8%) developed PDPH. Two (3%) were less than 6 years old and four (5%) were 6 to 12 years of age. Children with a history of headache following a previous LP were nine times as likely to experience PDPH. PDPH occurs not infrequently in children. A prior history of headache is a predisposing factor.
Assuntos
Cefaleia/etiologia , Injeções Epidurais/efeitos adversos , Neoplasias/fisiopatologia , Punção Espinal/efeitos adversos , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Postura , RecidivaRESUMO
PURPOSE: The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival. PATIENTS AND METHODS: Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP). RESULTS: The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not. CONCLUSION: EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Extremidades , Osteossarcoma/tratamento farmacológico , Adolescente , Bleomicina/administração & dosagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Quimioterapia Adjuvante , Criança , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Intervalo Livre de Doença , Humanos , Metotrexato/administração & dosagem , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Vincristina/administração & dosagemRESUMO
Neutrophilic dermatosis (Sweet syndrome) is a rare condition characterized by painful indurated cutaneous plaques infiltrated with mature neutrophils and may be accompanied by fever, granulocytosis, arthritis, and conjunctivitis. It is associated with various malignant and preneoplastic states, the most common being leukemia and myeloproliferative disorders. Its association with solid tumors is infrequent. The case described here represents, to our knowledge, the first report of Sweet syndrome in a patient with osteogenic sarcoma, a primary tumor of bone arising from mesenchymal cells.
Assuntos
Neoplasias Ósseas/complicações , Osteossarcoma/complicações , Síndrome de Sweet/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Recidiva Local de Neoplasia , Neutrófilos/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/secundário , Síndrome de Sweet/patologiaRESUMO
Relapsed Wilms tumor is often very responsive to re-treatment, and cures are possible in many cases. Recurrent Wilms tumor forms a heterogeneous group because initial therapies vary widely. Given the complexity of the problem, there is a great need for an organized clinical investigative approach. Ideally, the treatment of initial relapse should be specified by the primary treatment protocol in order to better evaluate overall survival as an end-point for new primary therapy strategies. This is especially appropriate for Wilms tumor, because the investigations of this tumor over the last 20 years have attempted to determine the minimal therapy necessary for cure. Thus, survival rather than relapse-free survival is the most appropriate criterion for the success of a primary retreatment regimen. This investigative approach would also allow evaluation of treatment strategies tailored to a specific patient population. Important questions remain for those who treat recurrent Wilms tumor. Defining the role of high-dose therapy, defining the role of total body irradiation in high-dose therapy regimens, and defining the benefit and toxicity of cyclophosphamide compared with ifosfamide are three current questions under investigation. Developing new agents and regimens effective against Wilms tumor, especially against anaplastic tumors, RTK, and CCSK, is extremely important if progress is to be made in treating these tumors after relapse. Finally, there is a strong need to develop biologic information about tumors that recur, so not only will we better understand why patients relapse but also we can develop therapy tailored specifically to the biology of the recurrent tumor.
Assuntos
Neoplasias Renais/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Primárias Múltiplas/terapia , Tumor de Wilms/terapia , Antineoplásicos/uso terapêutico , Terapia Combinada , Humanos , PrognósticoRESUMO
Among Ewing's sarcoma (ES) of bone and related entities are tumours with neuro-ectodermal features that could represent a biologically distinct type. In order to assess the prognostic significance of the various forms of ES, a retrospective joint study involving three cancer centres in Europe and the U.S.A. was initiated. The material from 315 primary ES was reviewed by a panel of five pathologists and classified as typical ES (220 cases), atypical ES (48 cases) or ES with neuro-ectodermal features (47 cases). Prognostic factor analysis on treatment failure-free survival was performed using the Cox model. It included histopathological classification, initial patient characteristics, clinical presentation and treatment type. After multivariate analysis, in addition to treatment type (P < 0.001), metastases (P = 0.003) and proximal tumour location (P = 0.006), two histopathological parameters correlated with poor treatment failure-free survival, the presence of filigree pattern (P = 0.044) and dark cells (P = 0.043). We conclude that ES with neuro-ectodermal features does not appear to have a different outcome to the other subtypes.
Assuntos
Neoplasias Ósseas/patologia , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Sarcoma de Ewing/patologia , Adolescente , Adulto , Análise de Variância , Neoplasias Ósseas/terapia , Diferenciação Celular , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroectodérmicos Primitivos Periféricos/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcoma de Ewing/terapia , Método Simples-CegoRESUMO
Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) are small blue cell tumors with no reliable positive diagnostic markers. However, Ewing's sarcoma and PNET recently have been shown to strongly express an antigen determined by the MIC2 gene, whereas other blue cell tumors of childhood for the most part do not. MIC2 analysis therefore offers a distinctive addition to the panel of immunohistochemical stains used to differentiate among small blue cell tumors of childhood, since it represents the first positive marker for Ewing's sarcoma and PNET. This study addresses the reliability of MIC2 analysis using the monoclonal antibody 12E7 on tumors registered in the current Intergroup Ewing's Sarcoma protocol. Of 244 tumors, 221 (91%) showed a diffuse strong membranous pattern. The antibody appears to withstand all the fixation variables inherent in a multi-institutional study. We conclude that MIC2 expression is highly reliable as a positive marker for the Ewing's sarcoma/PNET family of tumors when the results are interpreted in the total context with clinical and pathologic parameters.
Assuntos
Antígenos CD , Neoplasias Ósseas/diagnóstico , Moléculas de Adesão Celular , Glicoproteínas de Membrana , Sarcoma de Ewing/diagnóstico , Antígeno 12E7 , Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Neoplasias Ósseas/patologia , Moléculas de Adesão Celular/análise , Criança , Pré-Escolar , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/análise , Tumores Neuroectodérmicos Primitivos Periféricos/química , Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Sistema de Registros , Sarcoma de Ewing/química , Sarcoma de Ewing/patologiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Quimioterapia Adjuvante , Criança , Cisplatino/administração & dosagem , Protocolos Clínicos , Terapia Combinada , Doxorrubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Ifosfamida/administração & dosagem , Tábuas de Vida , Masculino , Metotrexato/administração & dosagem , Minnesota/epidemiologia , Necrose , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Projetos Piloto , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Metotrexato/uso terapêutico , Osteossarcoma/tratamento farmacológico , Análise Atuarial , Bleomicina/administração & dosagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Quimioterapia Adjuvante , Criança , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Osteossarcoma/mortalidade , Osteossarcoma/cirurgia , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Vincristina/administração & dosagemRESUMO
Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A). 2'-Deoxycoformycin is an inhibitor of adenosine deaminase (ADA), an enzyme found in relatively high amounts in malignant lymphoid cells. Ara-A inhibits DNA polymerase and DNA synthesis. Because its efficacy in vivo as an anticancer agent is limited by its rapid inactivation by ADA, ara-A was combined with dCF to produce cytoreductive levels of ara-A. Twenty-four patients were assigned to receive dCF alone and 25 to receive the combination. No patient responded to dCF alone, and one patient developed a complete remission after treatment with the combination. The toxicity of dCF alone was minimal, except for one patient who became obtunded on day 5 following the first cycle of therapy. In contrast, five patients developed severe toxicity with the combination, including renal failure (three patients), hepatic failure (three patients), and neurologic toxicity (two patients). These results indicate that, at the doses and schedule used in this study, the combination of dCF and ara-A has significant toxicity and minimal activity against recurrent ALL in children.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Pentostatina/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Sinergismo Farmacológico , Humanos , Imunofenotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Recidiva , Vidarabina/administração & dosagemRESUMO
We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture.
Assuntos
Rabdomiossarcoma/classificação , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Análise Multivariada , National Institutes of Health (U.S.) , Prognóstico , Análise de Regressão , Rabdomiossarcoma/patologia , Estatística como Assunto , Estados Unidos , Organização Mundial da SaúdeRESUMO
Fourteen patients with refractory advanced neuroblastoma were treated with 131-I-metaiodobenzylguanidine (131-I-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Iodobenzenos/uso terapêutico , Neuroblastoma/radioterapia , 3-Iodobenzilguanidina , Adolescente , Adulto , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/efeitos adversos , Iodobenzenos/administração & dosagem , Iodobenzenos/efeitos adversos , Masculino , Estadiamento de Neoplasias , Neuroblastoma/patologia , Terapia de Salvação , Análise de SobrevidaRESUMO
We report a case of Wilms' tumor associated with urinary extravasation due to tumor invasion through the renal pelvis and anterior renal capsule. Extravasation of urine exposed to tumor may lead to upstaging of the tumor and the requirement for more intensive therapy.
Assuntos
Nefropatias/etiologia , Neoplasias Renais/complicações , Túbulos Renais Coletores , Tumor de Wilms/complicações , Feminino , Humanos , Lactente , Nefropatias/diagnóstico , Nefropatias/urina , Neoplasias Renais/diagnóstico , Neoplasias Renais/urina , Espaço Retroperitoneal , Ruptura Espontânea , Tumor de Wilms/diagnóstico , Tumor de Wilms/urinaRESUMO
We treated 31 children with acute lymphoblastic leukemia (ALL), 14 children with acute nonlymphoblastic leukemia (ANLL) in relapse, and 1 child with chronic myelogenous leukemia (CML) in blast crisis (CALLA negative) with indicine N-oxide in a Phase II study. The efficacy and toxicity of the drug were assessed at two dose levels: 2,000 mg/m2/day for 5 consecutive days (14 patients) and 2,500 mg/m2/day for 5 consecutive days (17 patients). One patient with ALL at each dose level achieved a complete response (CR) lasting 6 months and 1 month, respectively. The patient with CML achieved a partial response lasting 4 months. None of the patients with ANLL achieved a CR. Hepatotoxicity was mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of patients; 3 patients (9%) experienced severe hepatotoxicity. Although indicine N-oxide has some antileukemic activity in ALL and is safe at the doses used in this study, the antileukemic activity is significantly less at these two doses than at greater than or equal to 3,000 mg/m2/days for 5 consecutive days. Unfortunately, when the higher doses are administered to children, they are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity.