RESUMEN
PURPOSE: The combination of bevacizumab and FOLFIRINOX is used in patients with RAS-mutant metastatic colorectal cancer (RASm-mCRC). Regorafenib, an oral multi-tyrosine kinase inhibitor, has antiangiogenic properties, cytostatic effects and also true cytotoxic effects, unlike bevacizumab. The aim of this study was to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the regorafenib-FOLFIRINOX combination in patients with RASm-mCRC. METHODS: The FOLFIRINOX-R trial was a phase 1/2 study where the dose-escalation part (3 + 3 design with three dose levels, DLs) was completed before its early termination. FOLFIRINOX (14-day cycle) included oxaliplatin (standard dose), folinic acid, fluorouracil and irinotecan (150 or 180 mg/m²). Regorafenib (120 or 160 mg daily) was given from day 4 to day 10 of each cycle. Dose-limiting toxicity (DLT) was studied in the first three cycles. Eligibility criteria included ECOG performance status ≤ 1 and not previously treated RASm-mCRC. RESULTS: Thirteen patients (median age: 65 years; min-max: 40-76) were enrolled. DLT could not be evaluated in one patient (DL3) due to poor observance. The median treatment duration and median follow-up were 6.2 (min-max: 2.3-10) and 13.4 (min-max: 3.8-18.0) months, respectively. Dose was modified in 12/13 (92%) patients. One grade 3 hypokalemia occurred at DL2. MTD was not reached at DL3. Grade 3 diarrhea was recorded in 7/13 patients (13 events) equally distributed in all DLs. CONCLUSION: The RP2D for this regorafenib-FFX combination could not be determined due to a high prevalence of grade 3 diarrhea related to treatment as advised by our Independent Data Monitoring Committee. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov : NCT03828799.
RESUMEN
Objetivo. Evaluar la eficacia de dos estrategias educativas para la prevención del tabaquismo en jóvenes de edad escolar. Material y métodos. Estudio de intervención, de comparación concurrente, con alumnos del quinto grado de primaria durante los cursos de 1992 a 1995, efectuado en el Departamento del Herault, Montpellier, Francia. Se incluyeron tres grupos de observación: grupo I, sometido durante el año escolar a un programa educativo transversal; grupo II, sometido el "Día Mundial sin Fumar" a una acción puntual, y el grupo III, testigo, no sometido a intervención, cuyos resultados se compararon con ji cuadrado y se hizo regresión logística. Resultados. Se confirma el papel pronóstico de sus iguales y del entorno familiar sobre el consumo de tabaco. Transcurridos tres años, el grupo sometido a la intervención transversal sostenida muestra una prevalencia de fumadores significativamente inferior a la de los otros dos grupos. Conclusiones. Aunque el consumo de tabaco parece iniciar más tardíamente en las niñas que en los niños, en este estudio la prevalencia aumenta al cabo de tres años, de 0.7 a 7 por ciento. Deben mantenerse y reforzarse en tiempo y lugar las acciones educativas de prevención para que tengan influencia y eficacia en la iniciación y disminución del consumo de tabaco en los niños.
Abstract Objective. To evaluate the efficacy of two educational strategies to prevent tobacco addiction in schoolchildren living in Herault, France. Material and Methods. A study was conducted to deliver an intervention and make a concurrent comparison, among elementary school, fifth-grade students, during school years 1992 to 1995, in Herault Department, Montpellier, France. Three observation groups were included: Group 1 was subject to a cross-sectional educational intervention; Group 2 was only subject to a single health activity on World Day Against Smoking; and Group 3 or control was not subject to any intervention. Results. The prognostic role of peers and the family setting on tobacco consumption was confirmed; after three years, the Group subject to the sustained cross-sectional intervention showed a prevalence of smokers significantly lower than that of the other two groups. Conclusions. Even though tobacco consumption seems to begin earlier in boys than in girls, in the former the prevalence increases from 0.7 to 7 percent after three years. Preventive educational interventions should be maintained and reinforced to be effective on the initiation and cessation of tobacco smoking among children.