Effectiveness, safety, and prognostic factors of trifluridine/tipiracil for the treatment of patients with metastatic colorectal cancer in routine clinical practice.

Background: The combination of trifluridine and tipiracil is indicated in patients with metastatic colorectal cancer previously treated or non-candidates to chemotherapy and biological therapies. This study in routine clinical practice aimed to describe the effectiveness and safety of trifluridine and tipiracil and identify prognostic factors in patients with metastatic colorectal cancer in Spain. Methods: This analysis was a retrospective, observational, multicenter study that included patients aged ≥18 years who had received treatment with trifluridine/tipiracil for metastatic colorectal cancer in third- or subsequent lines. Results: Overall, 294 were evaluated. Trifluridine/tipiracilmedian (minimum, maximum) treatment duration was 3.5 (1.0-29.0) months, and 128 (43.5%) patients received subsequent treatments. One hundred (34%) patients showed disease control rate, and the median progression-free survival and overall survival from trifluridine/tipiracil treatment onset were 3.7 and 7.5 months, respectively. The most frequently reported adverse events were asthenia (all grades, 57.9%) and neutropenia (all grades, 51.3%). A 39.1% and 4.4% of the participants had a dose reduction and a treatment interruption due to toxicity. Patients with age ≥65 years, low tumor burden, ≤2 metastasis sites, treatment dose reduction, neutropenia, and ≥6 cycles, had significantly higher overall survival, progression-free survival, and response rate. Conclusions: This real-life study indicates that trifluridine/tipiracil shows effectiveness and safety in treating patients with metastatic colorectal cancer. The results show a profile of metastatic colorectal cancer patients with previously unknown prognostic factors who have a more significant benefit from treatment with trifluridine/tipiracil in routine clinical practice.

Ruta biocultural de conservación de las semillas nativas y criollas en el territorio indígena de Puracé, Cauca / Biocultural route for the conservation of native and creole seeds in the indigenous territory of Puracé, Cauca

RESUMEN Buscar la conservación de los sistemas productivos tradicionales en el territorio de Puracé implicó identificar los principales factores que los han afectado y definir estrategias, que posibiliten su conservación. En el resguardo, el esfuerzo de conservación, se realiza a través de una organización, de hecho, que pertenece al cabildo indígena, denominada custodios de semillas. Por esta razón, el trabajo se focalizó con ellos, con quienes se realizaron talleres, entrevistas y trabajo de campo, que involucraron observación participante, etnografías, caracterización etnobotánica y análisis cartográficos, lo que llevó a generar una Ruta biocultural de conservación de las semillas nativas y criollas. Se identificaron 156 semillas, que fueron etnoclasificadas, 90 de uso culinario, 37 medicinales, 16 usadas para alimento y medicina y 13 con otros usos; los factores bioculturales que afectan la conservación, se agruparon en 5 categorías; el relevo generacional es el principal factor cultural, sobre el cual, es necesario trabajar para la conservación de las semillas nativas y criolla, por lo que constituye el eje estructurante de la Ruta que se propuso.

ABSTRACT Seeking the conservation of traditional production systems in the Puracé reservation, implied identifying the main factors that have affected them and defining strategies that enable their conservation. In the reservation, the conservation effort is carried out through an organization in fact that belongs to the indigenous council, called custodians of seeds. For this reason, the work was focused on them, with whom workshops, interviews and field work were carried out that involved participant observation, ethnographies, ethnobotanical characterization and cartographic analysis, leading to establish the need to generate a biocultural route for the conservation of native seeds. and Creoles. 156 seeds were identified that were ethnoclassified, 90 for culinary use, 37 medicinal, 16 used for food and medicine, and 13 for other uses; The factors that affect conservation were grouped into 5 categories, the generational change is the main factor on which it is necessary to work is conservation, constituting the structuring axis of the Route that was proposed.

Real-world experience of everolimus as second-line treatment in metastatic renal cell cancer after failure of pazopanib.

AIM: We aimed to provide real-life data on the outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus as second-line treatment after failure of first-line pazopanib. PATIENTS AND METHODS: Data from the medical charts of mRCC patients from 8 centers in Greece and Spain were reviewed. All patients had received or were continuing to receive second-line everolimus treatment after failure of first-line treatment with pazopanib. No other previous therapies were allowed. The primary end point was the determination of progression-free survival (PFS). RESULTS: In total, 31 patients were enrolled. Of these, 26% had performance status (PS) >0, 88% were of intermediate/poor Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, and only 61% had undergone prior nephrectomy. Median PFS was 3.48 months (95% CI: 2.37-5.06 months). Median overall survival (OS) from everolimus initiation was 8.9 months (95% CI: 6.47-13.14 months). Median OS from pazopanib initiation was 14.78 months (95% CI: 10.54-19.08 months). Furthermore, 32% of patients temporarily discontinued everolimus due to adverse events (AEs), and 22% of patients discontinued everolimus permanently due to toxicity. Most common toxicities were anemia (29%), stomatitis (26%), pneumonitis (19%), and fatigue (10%). Moreover, 14 AEs (27%) were graded as 3 or 4 and were reported by 13 patients (42%). CONCLUSION: This study provides data exclusively on the sequence pazopanib-everolimus in mRCC. Everolimus has a favorable safety profile and is active. The short PFS and OS could be attributed to the fact that the pazopanib-everolimus sequence was mainly offered to patients with adverse prognostic features, resulting in a modest increase in the combined OS of our population.

A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis.

We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein-1alpha genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti-MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis-stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis-stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.