RESUMEN
BACKGROUND: The aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway. PATIENTS AND METHODS: In a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway. RESULTS: The median age of the 58 patients enrolled into the study was 60 years (range 41-78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)]. CONCLUSIONS: The PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials.
Asunto(s)
Carcinoma Papilar/genética , Carcinoma de Células Renales/genética , Everolimus/uso terapéutico , Neoplasias Renales/genética , Fosfatidilinositol 3-Quinasas/genética , Serina-Treonina Quinasas TOR/genética , Adulto , Anciano , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/mortalidad , Carcinoma Papilar/secundario , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Fosfatidilinositol 3-Quinasa Clase I , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Clasificación del Tumor , Inhibidores de las Quinasa Fosfoinosítidos-3 , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Tasa de Supervivencia , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
AIMS: The study attempted to evaluate the kinetics of changes in serum TRAIL levels as a potential predictive and prognostic factor in patients with epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC), eligible for an interval debulking surgery (IDS). MATERIAL AND METHODS: 17 patients with primary inoperable EOC or PPC in FIGO Stage IIIC or IV who underwent an exploratory operation were enrolled to the study. Serum TRAIL levels were determined by ELISA method (DIACLONE, Besancon Cedex, France) before and after two courses of neoadjuvant chemotherapy (NAC) based on paclitaxel and platinum analogue (cisplatin or carboplatin). The control group consisted of six healthy volunteers. The median difference in concentration of TRAIL (dTRAIL) between the initial marking and after two courses of NAC in each patient was 192 pg/ml and it was used for dichotomization of the test group. RESULTS: Suboptimal interval debulking surgery (IDS) was performed in 23.5% (4/17) and optimal IDS in 76.5% (13/17) patients. TRAIL concentration before chemotherapy did not differ significantly between patients with EOC or PPC [1426.96 +/- 321.06 pg/ml (mean +/- SD) (U = 26, p = 0.08)] and the control group [1160.40 +/- 256.39 pg/ml (mean +/- SD. After two courses of NAC serum TRAIL concentration level was 1247.49 +/- 378.46 pg/ml (mean +/- SD). The difference was significant (Z = 2.44, p = 0.0147). Statistical analysis showed that dTRAIL did not significantly influence either extent of IDS (U = 35, p = 0.0962) or time to progression (log-rank test, p = 0.1185), overall survival (log-rank test, p = 0.1973) and response to treatment according to RECIST criteria (U = 35.5, p = 0.9616). CONCLUSIONS: Serum TRAIL concentration levels changed significantly during NAC. However, it seems that the concentration of this protein has no critical value as a predictive or prognostic factor in patients with EOC or PPC.
Asunto(s)
Terapia Neoadyuvante , Neoplasias Glandulares y Epiteliales/sangre , Neoplasias Ováricas/sangre , Neoplasias Peritoneales/sangre , Ligando Inductor de Apoptosis Relacionado con TNF/sangre , Adulto , Anciano , Carcinoma Epitelial de Ovario , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/mortalidad , Proyectos PilotoRESUMEN
Pleural effusion is a clinical problem considered by internists from the diagnostic point of view. Physiology of pleural cavity and its pathophysiology are of great interest for clinicians. Diagnostic procedures give the possibilities to find a culprit of pleural effusion. Moreover, oncologists seek the best treatment procedures to fight against the pleural effusion.
Asunto(s)
Derrame Pleural/diagnóstico , Derrame Pleural/terapia , Terapia Combinada , HumanosRESUMEN
Tumor Necrosis Factor alfa (TNFa) is a cytokine with cytolytic and cytotoxic properties. First clinical trials in which TNF was administered parenterally date back to early 70-ties. Soon it was noticed that when administered strictly to the tumor mass TNF exhibits high anti-tumor efficacy, exemplified by total or at least substantial regression of the tumor mass while producing minor and controllable symptoms. In this paper the case of local administration of the recombinant TNFa directly into the tumor mass constricting the bronchus was presented.