RESUMO
Discovery of activating EGFR mutations led to dramatic modification of treatment schemes for nonsquamous lung cancer. 70 patients with activating EGFR mutations were treated by gefitinib being either a part of prospective phase II trial (n = 25) or, subsequently, subjected to routine clinical management (n = 45). Objective response rate approached to 32.7%. Median time to disease progression was 14 months, and median overall survival was 26.1 months. Subgroup analysis revealed statistically longer time to disease progression (p < 0,0001) and overall survival (p = 0,001) in latter vs. former group, despite the lower rate of objective response (22% vs 48%). Possible explanations include more relaxed standards for routine gefitinib use, i.e. inclusion of the patients with non-measurable tumor lumps, continuation of gefitinib uptake upon slow disease progression, and increasing availability and quality of radiosurgery for brain metastases.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Análise de Sobrevida , Resultado do TratamentoRESUMO
Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Barreira Hematoencefálica , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Desoxicitidina/análogos & derivados , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/etiologia , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Injeções Intraperitoneais , Masculino , Camundongos , Transplante de Neoplasias , GencitabinaRESUMO
The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.
