RESUMEN
BACKGROUND: FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) is an option for fit patients with metastatic (MPC) and locally advanced unresectable (LAPC) pancreatic cancer. However, no criteria reliably identify patients with better outcomes. PATIENTS AND METHODS: We investigated putative prognostic factors among 137 MPC/LAPC patients treated with triplet chemotherapy. Association with 6-month survival status (primary endpoint) was assessed by multivariate logistic regression models. A nomogram predicting the risk of death at 6 months was built by assigning a numeric score to each identified variable, weighted on its level of association with survival. External validation was performed in an independent data set of 206 patients. The study was registered at ClinicalTrials.gov (NCT03590275). RESULTS: Four variables (performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio) were found to be associated with 6-month survival by multivariate analysis or had sufficient clinical plausibility to be included in the nomogram. Accuracy was confirmed in the validation cohort (C index = 0.762; 95% confidence interval, 0.713-0.825). After grouping all cases, 4 subsets with different outcomes were identified by 0, 1, 2, or > 2 poor prognostic features (P < .0001). CONCLUSION: The nomogram we constructed accurately predicts the risk of death in the first 6 months after initiation of FOLFIRINOX in MPC/LAPC patients. This tool could be useful to guide communication about prognosis, and to inform the design and interpretation of clinical trials.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Nomogramas , Neoplasias Pancreáticas/mortalidad , Adulto , Anciano , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Numérico Asistido por Computador , Oxaliplatino/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Pancreatic adenocarcinoma (PA) is diagnosed in most cases at an advanced stage requiring chemotherapy. Folfirinox is the standard first-line treatment. After Folfirinox failure, gemcitabine alone is routinely used as second-line therapy without data supporting this attitude. AIM: Determine the response rate and outcome of patients with advanced PA treated with gemcitabine after Folfirinox failure. METHODS: We retrospectively analyzed all consecutive patients treated with gemcitabine after Folfirinox failure for a locally advanced or metastatic PA between 2009 and 2015. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Response rate, control rate and tolerability were assessed. RESULTS: 96 patients were included (male, 51%; median age, 62; performance status (PS) 0-1, 47%). Median duration on gemcitabine was 2.1 months. The overall disease control rate was 40%. Median OS was 3.7 months (95%CI: 2.5-5.2) and median PFS was 2.1 months (95%CI: 2.0-2.6). Reasons for treatment discontinuation were mostly progression (51%). Age at diagnosis and PS were independently associated with OS in multivariate analysis (HR of 1.86; p=0.0055 and 2.42; p<0.0001 respectively). 34 patients experienced a grade 3 adverse event. CONCLUSIONS: This study suggests that gemcitabine is not beneficial to all patients failing on Folfirinox first-line therapy and should be restricted to young patients with good PS.