Assuntos
Antivirais/efeitos adversos , Psoríase/induzido quimicamente , Exacerbação dos Sintomas , Adulto , Idoso , Carbamatos , Quimioterapia Combinada/efeitos adversos , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Psoríase/complicações , Pirrolidinas , Ribavirina/uso terapêutico , Simeprevir/efeitos adversos , Sofosbuvir/efeitos adversos , Valina/análogos & derivadosRESUMO
PURPOSE: hENT1 is a transmembrane protein which acts as a nucleoside transporter and is the main mediator of Gemcitabine (GEM) uptake into human cells. In this retrospective study we compared GEM versus FOLFIRINOX in patients with metastatic pancreatic cancer in which hENT1 evaluation was available. METHODS: 149 patients affected by unresectable metastatic pancreatic cancer, treated in our institution from 2009 to 2013, have been screened for inclusion in this retrospective study. Seventy patients, treated with GEM or FOLFIRINOX in first-line therapy, fulfilled clinical inclusion criteria for survival analysis. Thirty-one patients were available and contained sufficient quality/quantity RNA for evaluation of hENT1 expression by RT-PCR. The primary endpoint was OS and the secondary endpoint was PFS. RESULTS: The survival analysis, carried out on 70 patients regardless of hENT1 expression, showed a statistically longer OS and PFS in the group treated with FOLFIRINOX compared to GEM. Within the exploratory analysis, which included 31 patients, no differences were found in hENT1 positive patients treated with FOLFIRINOX compared to GEM in terms of OS (8.5 vs 7 months, HR: 0.89; 95 % CI 0.3-2.5; p = 0.8) and PFS (5.5 vs 5 months, HR: 0.8, 95 % CI 0.2-2.2; p = 0.61). GEM-treated hENT1 positive patients showed a statistically significant improvement both of OS (8 vs 2 months; p = 0.0012) and PFS (5 vs 1 months; p = 0.0004) in comparison to GEM-treated hENT1 negative patients. CONCLUSIONS: In our exploratory analysis GEM seems as effective as FOLFIRINOX in terms of survival with a better safety profile in hENT1 positive metastatic pancreatic cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Gencitabina , Neoplasias PancreáticasRESUMO
BACKGROUND: The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. PATIENTS AND METHODS: eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. RESULTS: Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. CONCLUSION: These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.
Assuntos
Bevacizumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Interleucina-8/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The effects of injury on peripheral nerve blood flow were studied, using a Laserflo blood perfusion monitor. A total of 11 nerves were studied, five normal and six injured nerves in four patients. Two of the patients had lacerating brachial plexus injuries, and two other patients had compressive neuropathies of their ulnar nerves at the elbow. All of the readings were taken intraoperatively while the patients were undergoing exploration and repair under general anesthesia. Measurements of the damaged nerves were taken serially from the site of injury proximally and distally, by approximating a flexible metric ruler to the dorsal aspect of the nerve along the same axis. In the acutely lacerated injured nerves (3 to 7 days), the measurements were taken at 1, 5, 10, and 20 mm. The maximal amount of retraction in any of the nerves was 1 cm; thus, the overall architecture of the nerves was maintained. In the compressed nerves, measurements were taken at 1, 2 and 3 cm proximal and distal to the medial epicondyle. Measurement of normal undamaged nerves was performed at six different sites along the same axis of the nerve. The averaged results indicate that the normal blood flow ranged from 47 ml/100 g/min to 63 ml/100 g/min, with a mean of 56 ml/100 g/min. In the injured nerves, blood flow was most depressed at sites closest to the laceration, and increased consistently and progressively at sites distant from the injury in both directions.(ABSTRACT TRUNCATED AT 250 WORDS)