RESUMEN
PURPOSE: Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making. METHODS: In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2- patients with 0-3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan-Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups. RESULTS: A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively. CONCLUSION: These survival analyses indicate that the postmenopausal node-negative ER+HER2- patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients.
Asunto(s)
Neoplasias de la Mama , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Humanos , Sobretratamiento , Posmenopausia , Pronóstico , Tamoxifeno/uso terapéuticoRESUMEN
Thirty-three metastatic melanoma patients were vaccinated according to a phase I-II study with an allogeneic melanoma cell line that was genetically modified by transfection with a plasmid containing the gene encoding human interleukin 2 (IL-2). The cell line expresses the major melanoma-associated antigens and the HLA class I alleles HLA-A1, -A2, -B8, and Cw7. All patients shared one or more HLA class I alleles with this cell line vaccine. Patients were immunized by three vaccinations, each consisting of 60 x 106 irradiated (100 Gy) melanoma cells (secreting 120 ng of IL-2/10(6) cells/24 hr) administered subcutaneously at weekly intervals for 3 consecutive weeks. Side effects of treatment consisted of swelling of locoregional lymph nodes and induration at the site of injection, i.e., a delayed-type hypersensitivity (DTH) reaction. In three patients, vaccination induced inflammatory responses in distant metastases containing necrosis or apoptosis along with T cell infiltration. Apoptosis occurred only in Bcl-2-negative areas, not in Bcl-2-expressing parts of the metastases. Two other patients experienced complete or partial regression of subcutaneous metastases. Seven patients had protracted stabilization (4 to >46 months) of soft tissue metastases, including one patient who developed vitiligo after vaccination. Immune responses to the vaccine could be detected in 67% of the 27 patients measured. Vaccination was shown to induce a variable change in the number of anti-vaccine cytotoxic T lymphocytes (CTLs) in peripheral blood, which did not correlate with response to treatment. However, in two of five patients the frequency of anti-autologous tumor CTLs measured was significantly higher than before vaccination. This study demonstrates the feasibility, safety, and therapeutic potential of vaccination of humans with allogeneic, gene-modified tumor cells, and that frequencies of vaccine-specific CTLs among patient lymphocytes can be determined by using a modified limited dilution analysis (LDA).
Asunto(s)
Vacunas contra el Cáncer/farmacología , Interleucina-2/metabolismo , Melanoma/secundario , Melanoma/terapia , Adulto , Anciano , Antígenos de Neoplasias/genética , Vacunas contra el Cáncer/genética , Femenino , Antígeno HLA-A1/metabolismo , Antígeno HLA-A2/metabolismo , Antígeno HLA-B8/metabolismo , Antígenos HLA-C/metabolismo , Humanos , Inmunoterapia/métodos , Inflamación/inmunología , Interleucina-2/genética , Interleucina-2/farmacología , Antígeno MART-1 , Masculino , Melanoma/mortalidad , Antígenos Específicos del Melanoma , Persona de Mediana Edad , Monofenol Monooxigenasa/genética , Proteínas de Neoplasias/genética , Tasa de Supervivencia , Linfocitos T Citotóxicos/inmunología , Resultado del Tratamiento , Células Tumorales CultivadasRESUMEN
BACKGROUND: Most patients with metastatic renal cell carcinoma (RCC) have undergone unilateral- and some bilateral nephrectomy. Because interleukin-2 (IL-2) is thought to be mainly cleared via the kidneys, we investigated whether IL-2 treatment is safe in anephric patients. PATIENTS AND METHODS: The pharmacokinetics of i.v. bolus, i.v. infusion and s.c. recombinant IL-2 were investigated in two anephric patients with progressive metastatic RCC. RESULTS: Following i.v. bolus administration of IL-2, plasma half-lives of 126 and 84 minutes respectively, and plasma clearances of 151 ml/min and 273 ml/min respectively, were measured in the two patients. In one patient plasma clearance of IL-2 was enhanced to 760 ml/min after continuous i.v. infusion of 4 and 6 million IU IL-2/24 hours, as compared to a clearance of 310 ml/min at a dose of 2 million IU IL-2/24 hours. In the other patient, during IL-2 infusion of 2, 4 or 6 x 10(6) IU/24 hours, each over the course of 3 days, plasma clearance of IL-2 increased from 311 to 761, and to 687 ml/min, respectively. IL-2 could not be detected in haemo- or peritoneal dialysates. CONCLUSIONS: IL-2 plasma half-life is only moderately prolonged in anephric patients as compared to patients with normal renal function. Based on our findings, intravenous or subcutaneous treatment of anephric patients with IL-2 seems feasible.
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Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Interleucina-2/farmacocinética , Interleucina-2/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Anciano , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Inyecciones Subcutáneas , Pruebas de Función Renal , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Nefrectomía , Resultado del TratamientoRESUMEN
A case history is presented concerning a 59-year-old female patient with chronic autoimmune neutropenia complicated by recurrent skin infections, mucositis, and conjunctivitis. For subjective reasons she refused treatment with prednisone, but eventually cyclosporine led to an important clinical improvement and an increase of the peripheral granulocyte count. Treatment modalities of autoimmune neutropenia are briefly discussed.
Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Ciclosporina/uso terapéutico , Neutropenia/inmunología , Femenino , Humanos , Persona de Mediana Edad , Neutropenia/tratamiento farmacológicoRESUMEN
Three methods for the examination of erythrocyte morphology in urine are described: phase contrast microscopy, microscopy of cytocentrifuged and stained preparations, and erythrocyte analysis with the Technicon H1. Analysis with the H1 has not been described until now. All methods can be used to discriminate between dysmorphic and isomorphic erythrocytes. The red cell distribution width was the best H1 parameter for this discrimination. The authors have found a good correlation between the microscopic methods. The clinical impact of the three methods was studied with urine samples from patients with a confirmed diagnosis. The discrimination between renal and nonrenal hematuria is similar with phase contrast microscopy and cytocentrifuged preparations. The use of the H1 for this discrimination is not recommended.