Adherence to capecitabine in preoperative treatment of stage II and III rectal cancer: do we need to worry?

BACKGROUND: Preoperative oral capecitabine plus radiotherapy has been progressively adopted in oncology units to provide more convenient care to patients with rectal cancer, but little is known about adherence to this therapy. PATIENTS AND METHODS: Prospective, multicentre observational study in six hospitals in metropolitan Barcelona (Spain), in patients with stage II and III rectal cancer. Assessment of adherence was based on the medical report in the clinical history, a patient questionnaire and a pill count in the pharmacy service upon finalization of treatment. Patients were considered adherent if they had taken 80%-110% of the prescribed treatment. We evaluated clinical variables, adverse effects, anxiety and depression (using the hospital anxiety depression scale [HADS]), and quality of life (EORTC QLQ-30). We analysed adherence-associated variables using a logistic regression model and concordance between adherence measures by means of the modified Kappa index. RESULTS: We included 119 participants. Adherence measures showed little concordance between the assessment methods used: adherence was 100% according to the clinical history, 83.2% according to self-report and 67.9% according to the pill count. In the multivariable analysis, the most relevant variable associated with non-adherence was anxiety prior to treatment (adjusted odds ratio [ORa] 6.96, 95% confidence interval [CI] 1.48-32.7). We did not observe any relevant association between adherence and clinical variables and baseline quality of life parameters. CONCLUSIONS: Adherence to short-term oral neoadjuvant treatment in rectal cancer may be a clinical problem, and it should be acknowledged and systematically evaluated by clinicians during treatment. The limited concordance between different measures of adherence highlights the challenges in monitoring it and the need to use different approaches to assess its impact in clinical practice.

EGFR ligands and DNA repair genes: genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer.

Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.

Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.

In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were selected using HapMap database and literature resources. Three tagging single-nucleotide polymorphisms in the AREG gene region (rs11942466 C>A, rs13104811 A>G, and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG rs11942466 C>A and rs9996584 C>T were also associated with overall survival (OS). The functional polymorphism, EGFR rs712829 G>T, was associated with progression-free and OS. Our findings support that intergenic polymorphisms in the AREG gene region might help to identify colorectal cancer patients that will benefit from irinotecan plus anti-EGFR therapy.

Enfermedad de Kawasaki. Actualización y revisión de la casuística en nuestro centro en los últimos 10 años / Kawasaki disease. Update and review of the casuistic in our center int he last 10 years

La enfermedad de Kawasaki (EK) es una vasculitis sistémica, aguda y autolimitada, con complicaciones potentcialmente peligrosas, que afecta principalmente a lactantes y niños pequeños (edad< 5 años), aunque también se observa en adolescentes y adultos. Es la principal causa de cardiopatía adquirida en niños de los países desarrollados; su incidencia es de 15,1/100.000 niños de edad < 5 años/año, siendo similar en EE.UU. y Europa. Sin tratmiento, hasta 25% de lso casos desarrolla ectasias o aneurismas coronarios, con riesgo de infarto agudo de miocardio y muerte súbita. Revisamos las manifestaciones clíncias, los criterios diagnósticos, el diagnóstico diferencial, el tratamiento y los marcadores predictivos de no respuesta al tratamiento con inmunoglobulinas. Finalmente, comentaremos los datos de un estudio descriptivo retrospectivo de lso casos de EK diagnosticados en nuestro centro desde enero de 2002 hasta diciembre de 2012 (AU)

Kawasakii disease (KD) is a systemic vasculitis, acute, self-limited, with potentially dangerous complications, which potentially dangerous complications, which manly affects infants and young children (age<5 years), but also seen in adolescents and adults. The EK is the leading cause o acquired heart disease in children in developed countries and their impact on our environment is 15.1/100,000 children < 5 years/year, similar to the U.S. and European countries. Without treatment, up to 25% fo cases of KD develop coronary ectasia or aneurysms with risk of acute myocardial infarction and sudden death. In this work we will review clincial manifestations, diagnostic criteria, differential diagnsois, therapy and predictive markers of non response immunoglobulins. We also present data of a retrospective study of children diagnosed in our center from January 2002 to December 2012 (AU)