RESUMO
Allogeneic hematopoetic stem cell transplantation yields improved long-term survival for patients with high-risk malignant and non-malignant hematologic disease. However, it is associated with high morbidity and mortality. A proportion of patients need intensive care due to infectious, immunological and/or toxic complications. The utility of intensive care unit (ICU) treatments as mechanical ventilation and renal replacement therapy for these patients is uncertain since mortality is high. We describe the most frequent complications and the treatment options concerning the ICU in recipients of allogeneic hematopoetic stem cells.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
Pulmonary diseases can occur across the entire disease spectrum of malignant hematologic systemic diseases. Although infectious processes of the lungs are common in these immunosuppressed patient collectives, noninfectious causes account for up to half of the pulmonary manifestations found in hematologic malignancies. Besides the frequent infections including opportunistic pathogens, a broad differential diagnosis including drug-induced lung injury by cytostatic substances, cytokines, and innovative immunotherapeutic agents, rarer transfusion of blood products and intrathoracic manifestations of the hematologic malignancy itself, have to be kept in mind. Finally, vascular complications can also lead to pulmonary reactions. Early and consistent diagnostics and treatment of the bronchopulmonary, intrathoracic and vascular complications within the framwework of hematologic systemic diseases can be essential for the patient's prognosis.
Assuntos
Doenças Hematológicas , Neoplasias Hematológicas , Pneumopatias , Doenças Hematológicas/complicações , Neoplasias Hematológicas/complicações , Humanos , Hospedeiro Imunocomprometido , Pulmão , Pneumopatias/complicaçõesRESUMO
Stupor and coma are clinical states in which patients have impaired responsiveness or are unresponsive to external stimulation and are either difficult to arouse or are unarousable. The term stupor refer to states between alertness and coma. An alteration in arousal represents an acute life-threatening emergency, requiring prompt intervention for preservation of life and brain function.
Assuntos
Transtornos da Consciência/diagnóstico , Transtornos da Consciência/terapia , Emergências , Nível de Alerta , Coma/classificação , Coma/diagnóstico , Coma/etiologia , Coma/terapia , Transtornos da Consciência/classificação , Transtornos da Consciência/etiologia , Diagnóstico Diferencial , Distúrbios do Sono por Sonolência Excessiva/classificação , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/etiologia , Escala de Coma de Glasgow , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Exame Neurológico , Prognóstico , Estupor/classificação , Estupor/diagnóstico , Estupor/etiologia , Estupor/terapia , Inconsciência/classificação , Inconsciência/diagnóstico , Inconsciência/etiologia , Inconsciência/terapiaRESUMO
Haploidentical haematopoietic SCT (HSCT) using T-cell-replete grafts and post-transplant high-dose CY has found increasing acceptance. Our purpose was to evaluate the feasibility and outcome of this strategy as second HSCT incorporating donor change for acute leukaemia relapse after a first allogeneic transplantation. The courses of 20 consecutive adults (median age 37 years, 12 male) with AML (n=14), ALL (n=5) and acute bi-phenotypic leukaemia (n=1) were analysed retrospectively. Conditioning consisted of fludarabine, CY and either melphalan or TBI or tresosulfan+/-etoposide. Engraftment was achieved in 17 (85%), and a second remission was induced in 15 patients (75%) on day +30. The rate of grade II-IV acute GvHD was 35%, while chronic GvHD occurred in five patients. Most commonly observed grade III-IV toxicities were mucositis (30%), hyperbilirubinemia (20%), elevation of transaminases (20%) and creatinine (20%), while invasive fungal infection affected 30%. One-year non-relapse mortality (NRM) was 36%. At a median follow-up of 17 months, estimated 1-year OS was 45%, and 1-year relapse-free survival was 33%. This strategy was feasible and allowed for successful engraftment with a moderate rate of toxicity. Early outcome and NRM are at least comparable with results after a second HSCT from HLA-matched donors without donor change at HSCT2.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Doadores de Tecidos , Transplante Homólogo , Adulto JovemRESUMO
Most anticancer medications are effective only in subgroups of patients. Despite considerable improvements in histopathological and molecular pathological diagnostics, tumor response in the individual patient still remains unpredictable. Measuring tumor shrinkage by cross-sectional imaging procedures in patients with metastatic cancer represents the current standard for documenting the effectiveness of anticancer therapy. In addition to the large number of different imaging procedures computed tomography (CT) is certainly the best established and most widely available technique for assessing tumor response. This manuscript reviews the necessity and rationality of imaging procedures for monitoring tumor response in patients with metastatic cancer.
Assuntos
Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Imageamento por Ressonância Magnética/métodos , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.
Assuntos
Doenças Biliares/etiologia , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Transplante de Fígado/efeitos adversos , Carga Viral , Adolescente , Adulto , Idoso , Doenças Biliares/cirurgia , Estudos de Coortes , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Hepacivirus/genética , Hepatite C/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
A 77 year-old man suffering from adominal pain and urinary retention with a long history of a multiple myeloma was admitted to the emergency room. The previous clinical course during various chemotherapies was affected by several serious infections. Surprisingly, the diagnostic investigation including ultrasound and computed tomography showed an acute appendicitis.
Assuntos
Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Apendicite/complicações , Apendicite/diagnóstico por imagem , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico por imagem , Doença Aguda , Idoso , Diagnóstico Diferencial , Humanos , Achados Incidentais , Masculino , UltrassonografiaRESUMO
HISTORY: A 70-year-old woman had been under oncological supervision for several years because of breast cancer with bone and lymph node metastases. For several weeks she had been treated for increasing vocal cord paresis of uncertain cause, requiring a tracheostomy, a speech cannula being inserted after eight days. Several days later the patient began to complain of dyspnea, but repeated inspection and cleaning of the cannula failed to reveal its cause. The increasingly anxious patient was given a benzodiazepine preparation to calm her. She was then transferred to the intensive care unit because of worsening respiratory insufficiency and impaired consciousness. DIAGNOSIS AND COURSE: A fiberoptic bronchoscopy was performed immediately, which revealed a black foreign body immediately distal to the tip of the tracheal cannula. The cannula was removed and the slightly sedated patient at once coughed up a large amount of bronchial secretion and a long, curved and fairly firm blood clot. Control bronchoscopy now revealed a flat, slightly hemorrhagic ulcer on the dorsal tracheal wall at the point where the cannula tip had made contact with the tracheal wall. CONCLUSION: Even trained personnel may have difficulty in recognizing intratracheal thrombi in patients with a tracheostomy. It is thus essential that an endoscopy is performed in patients with obstructive symptoms after a tracheostomy.
Assuntos
Broncoscopia , Dispneia/etiologia , Trombose/diagnóstico , Doenças da Traqueia/etiologia , Traqueostomia/efeitos adversos , Úlcera/etiologia , Idoso , Catéteres/efeitos adversos , Feminino , Tecnologia de Fibra Óptica , Humanos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/cirurgia , Trombose/etiologia , Trombose/cirurgia , Doenças da Traqueia/complicações , Doenças da Traqueia/cirurgia , Úlcera/complicações , Paralisia das Pregas Vocais/cirurgiaAssuntos
Neoplasias Brônquicas/diagnóstico , Tumor Carcinoide/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Compostos Organometálicos , Complicações Neoplásicas na Gravidez/diagnóstico , Adulto , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Tumor Carcinoide/secundário , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Tomografia por Emissão de Pósitrons , Gravidez , Compostos Radiofarmacêuticos , Técnica de Subtração , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory. METHODS: Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m(-2) plus vinorelbin 25 mg m(-2) on days 1+8 (GemVin), or plus cisplatin 30 mg m(-2) on days 1+8 (GemCis), or plus capecitabine 650 mg m(-2) b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate. RESULTS: A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ≥grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis). CONCLUSIONS: This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
BACKGROUND: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals. RESULTS: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance. CONCLUSION: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Administração Oral , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Feminino , Humanos , Injeções Intravenosas , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Trastuzumab , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
While metastatic breast cancer is a systemic disease in most patients, there is a smaller subset of patients who suffer from oligometastatic disease defined by single or few resectable metastases. After verification of disease stabilization by systemic therapy, locoregional treatment such as surgery or radiation can be applied. While large prospective trials are missing to support the beneficial effect of this strategy, retrospective analyses are highly suggestive offering rapid disease control and even long-term survival in selected patients.
Assuntos
Neoplasias da Mama/terapia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Diagnóstico por Imagem , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Prognóstico , Taxa de SobrevidaAssuntos
Equimose/etiologia , Dermatoses do Pé/etiologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/cirurgia , Doenças Pulmonares Intersticiais/etiologia , Exame Neurológico/efeitos adversos , Pancitopenia/etiologia , Reflexo de Babinski , Insuficiência Respiratória/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Pressão/efeitos adversos , Trombocitopenia/diagnósticoRESUMO
This retrospective study analyzes, whether patients suffering from extensive hepatic metastatic disease treated with SIRT can become suitable candidates for RFA.Within 38 months 46 patients (26 female, 20 male; age 32-75 years) bearing an extensive hepatic metastatic disease were treated with SIRT. Patients suffered from metastases of breast cancer (16/46), colorectal cancer (CRC) (21/46), neuroendocrine (3/46), and other primary carcinomas (6/46). The indication for SIRT was otherwise untreatable metastases confined to the liver. Forty-three patients received single-session whole-liver radioembolization treatment using Yttrium90 resin microspheres with a mean activity of 2.13GBq. In 1 patient SIRT was confined to the left and in 2 patients to the right liver lobe. In 3 patients major complications (2/3 gastric ulceration and 1/3 oedematous pancreatitis) and in 24 patients minor complications occurred (acute abdominal/epigastric pain and/or nausea). Follow-up CT and/or MRI were obtained in 44 of 46 patients. In 5 of 44 patients tumor load decreased substantially (3/5 breast cancer, 1/5 CRC and 1/5 pancreatic cancer) making RFA feasible. The patients were referred for RFA after the first 3-month follow-up. RFA of the liver was successful in all cases in terms of complete ablation. In selected patients radioembolization is able to downstage liver metastases to an extent making a subsequent RFA suitable and therefore allows increasing the number of patients with a "complete response" after a minimally invasive therapy.
Assuntos
Neoplasias da Mama/fisiopatologia , Carcinoma Neuroendócrino/fisiopatologia , Ablação por Cateter , Neoplasias Colorretais/fisiopatologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Microesferas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Radioisótopos de ÍtrioAssuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzenossulfonatos/administração & dosagem , Bevacizumab , Cetuximab , Terapia Combinada , Progressão da Doença , Epotilonas/administração & dosagem , Humanos , Lapatinib , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Niacinamida/análogos & derivados , Panitumumabe , Compostos de Fenilureia , Prognóstico , Piridinas/administração & dosagem , Quinazolinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorafenibe , Taxa de SobrevidaAssuntos
Neoplasias Pancreáticas/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Cetuximab , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Farnesiltranstransferase/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Genes ras/fisiologia , Humanos , Metaloproteases/antagonistas & inibidores , Biologia Molecular , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia , GencitabinaRESUMO
BACKGROUND: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. PATIENTS AND METHODS: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. RESULTS: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. CONCLUSION: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Desoxicitidina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Desoxicitidina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Seleção de Pacientes , Trombocitopenia/induzido quimicamente , GencitabinaRESUMO
Atypical presentation of Churg-Strauss syndrome includes lymph-node and parenchymatous organ involvement which mimics the clinical presentation of lymphoproliferative disorders.A 54-year old man with a history of a low-grade follicular lymphoma presented with rapidly growing abdominal lymph-nodes and hepatic, renal and pulmonary infiltrations. CT guided biopsies to verify either lymphoma or infections showed eosinophilic, necrotizing, granulomatous vasculitis leading to the diagnosis of atypical Churg-Strauss syndrome. Within a few days of cyclophosphamide and prednisone treatment the clinical presentation improved and imaging studies detected regression of all manifestations during follow-up.
Assuntos
Síndrome de Churg-Strauss/diagnóstico , Doenças Linfáticas/etiologia , Linfoma Folicular/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Terapia Combinada , Diagnóstico Diferencial , Progressão da Doença , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/radioterapia , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Tomografia Computadorizada por Raios XRESUMO
Leptomeningeal carcinomatosis represents a rare manifestation of metastatic breast cancer (MBC). A 39-year-old female presenting with HER2-overexpressing MBC and suffering from meningeal carcinomatosis was treated with the humanized antibody trastuzumab directed to HER2 by intrathecal administration. The patient was diagnosed with HER2-overexpressing stage III breast cancer in December 2003. In August 2004, the patient developed a singular intracerebral metastasis which was resected by neurosurgery followed by whole-brain radiotherapy. Since MRI and cerebrospinal fluid (CSF) analyses indicated meningeal carcinomatosis, the patient was commenced on trastuzumab (6 mg/kg q3w) and capecitabine (2.500 mg/m2 d1-14, q3w). Prompted by clinical deterioration, 5 repeated doses of intrathecal methotrexate (15 mg/dose) were administered, yet without clinical improvement. There is initial evidence that trastuzumab does not reach an adequate concentration in CSF after intravenous application. Nevertheless, infiltration of trastuzumab into CSF is facilitated under conditions of an impaired blood-brain barrier, as it is known for meningeal carcinomatosis. For patients with leptomeningeal disease, intrathecal application of trastuzumab may provide an interesting therapeutical approach for patients with HER2 overexpressing metastatic breast cancer. Therefore, an Ommaya reservoir for intrathecal treatment with trastuzumab was placed surgically and intrathecal therapy was begun with escalating doses of trastuzumab (5-20 mg), which proved to be effective and well tolerated by the patient. Within 2 weeks after treatment, the patients' condition improved significantly and cell counts in CSF obtained from the Ommaya reservoir remained low for 11 months after first diagnosis of meningeal carcinomatosis when clinical symptoms and MRI indicated progression of meningeal and cerebral disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias Meníngeas/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/análogos & derivados , Humanos , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/secundário , Metotrexato/administração & dosagem , Receptor ErbB-2/imunologia , TrastuzumabRESUMO
The intention of this retrospective analysis was to describe the characteristics of patients with brain metastasis (BM) receiving trastuzumab for HER2 overexpressing metastatic breast cancer (MBC). A specific focus was the relation of BM occurrence to remission status of visceral disease during trastuzumab treatment. Patients with MBC presenting between March 2000 and May 2004 were included in this retrospective analysis. HER2 overexpression was determined by immunohistochemistry (IHC; DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Among 136 HER2 overexpressing patients (DAKO score 3+), 42 patients with BM were identified during follow-up (30.9%). Negative hormone receptor expression (estrogen receptor (ER) and progesterone receptor (PgR)) correlated with incidence of BM (42.8% vs. 23.4%; P=0.01). There was no correlation of the development of BM with regard to tumor grading and patient age. In patients who developed BM, the median interval between visceral and brain metastasis was 14 months (range 0-69 months). At the time BM was diagnosed, 14 out of 42 patients responded to trastuzumab-based treatment schedules (OR: 33.3%, 95% CI 18.5-48.2%). Median survival from diagnosis of BM was 13 months (range 0-60 months). The median overall survival calculated from first diagnosis of metastasis was not significantly shorter in patients with BM than in patients without BM (37 vs. 47 months; P=0.07 log rank). Trastuzumab is highly effective for the treatment of liver and lung metastasis in HER2 overexpressing patients, while it is apparently ineffective for treating or preventing BM. Since one third of HER2 overexpressing patients with MBC developed BM despite effective trastuzumab treatment, new treatment strategies and closer surveillance may be warranted for these patients.