Análisis crítico de la literatura. ¿En pacientes adultos con cáncer diferenciado de tiroides y progresión en los últimos 14 meses, el tratamiento con sorafenib comparado con placebo mejora la supervivencia? Estudio DECISION
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Keywords

inhibidores de tirosina cinasa
carcinoma de tiroides
sorafenib
medicina basada en la evidencia
tyrosine kinase inhibitors
evidence-based medicine
thyroid carcinoma

How to Cite

Román González, A., & Sanabria, Álvaro. (2017). Análisis crítico de la literatura. ¿En pacientes adultos con cáncer diferenciado de tiroides y progresión en los últimos 14 meses, el tratamiento con sorafenib comparado con placebo mejora la supervivencia? Estudio DECISION. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 2(3), 30–34. https://doi.org/10.53853/encr.2.3.93

Abstract

Introducción: El carcinoma de tiroides es el cáncer endocrino más frecuente. Las opciones terapéuticas cuando hay enfermedad progresiva, sintomática y resistente al yodo radioactivo son mínimas y poco efectivas. El sorafenib es una terapia aprobada para estos pacientes con base en los resultados del estudio DECISION. Se hace una revisión crítica acorde con los principios de medicina basada en la evidencia del estudio que llevó a la aprobación de este medicamento.
Título del estudio: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-28 (1)
Métodos: Ensayo clínico aleatorizado, financiado por Bayer HealthCare Pharmaceuticals y Onyx Pharmaceuticals, asignación oculta.
Pacientes y resultados: 419 pacientes mayores de 18 años con cáncer de tiroides localmente avanzado o cáncer de tiroides diferenciado metastásico refractario a yodo (papilar, folicular, incluyendo el de células de Hürthle y pobremente diferenciado), con progresión en los últimos 14 meses de acuerdo con los criterios de RECIST, al menos una lesión medible por TAC o por RM, ECOG 0–2; con función renal, medular y hepática normal y TSH menor de 0,5 mIU/L. El cáncer de tiroides refractario a yodo se definió como la presencia de al menos una lesión sin captación de yodo o pacientes con tumores yodo captantes y, bien sea, progresión luego de un tratamiento con yodo radioactivo en los últimos 16 meses o progresión luego de dos tratamientos con yodo recibidos con menos de 16 meses de diferencia (la última dosis recibida más de 16 meses antes) o una dosis acumulada de yodo de al menos 22,3 GBq (?600 mCi). Se excluyeron pacientes que habían recibido previamente terapia dirigida, talidomida o quimioterapia para cáncer de tiroides, cirugía previa o trauma en los 30 días previos al inicio del medicamento, antecedente de cáncer de piel, cérvix o vejiga en los últimos cinco años, cáncer indiferenciado de tiroides, úlceras, infección activa o sangrado en los últimos tres meses, historia de hemorragia, infiltración traqueal, bronquial o esofágica; cardiopatía o hipertensión arterial no controlada, infección por VIH o hepatitis, embarazo o lactancia y alergia al sorafenib. Se permitieron dosis bajas de quimioterapia para radiosensibilización. El desenlace primario fue la supervivencia libre de progresión (cada ocho semanas) con criterios RECIST y los secundarios fueron supervivencia global, tiempo para la progresión, tasa de respuesta objetiva (parcial o completa), tasa de control de la enfermedad (parcial, completa o estable ?4 semanas/6 meses) y duración de la respuesta. La supervivencia libre de progresión fue mayor en el grupo de sorafenib que en el grupo de placebo (10,8 meses vs. 5,8 meses, HR 0,59 – IC 95% 0,45-0,76 p<0,0001). El grupo de sorafenib tuvo una mayor tasa de eventos adversos (98,6 vs. 87,6%).
Conclusión: Sorafenib mejora significativamente la supervivencia libre de progresión comparado con placebo en pacientes con cáncer de tiroides diferenciado progresivo refractario a yodo radioactivo. La diferencia es pequeña. Los eventos adversos son frecuentes. No se reporta calidad de vida o mejoría sintomática. Esta terapia debe ser usada por personas expertas y debe evaluarse individualmente cada caso, agotando las opciones disponibles para el paciente antes de someterlo a los riegos del tratamiento.

Abstract
Introduction: Thyroid carcinoma is the most frequent endocrine cancer. There are minimal therapeutic options once the disease is metastatic, progressive, symptomatic and radioactive iodine resistant. Sorafenib is a recent approved therapy for these patients based on the results of the DECISION trial. A critical review of this study is done according to the principles of evidence-based medicine.
Title of the study: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-28(1)
Methods: Randomized clinical trial. Financial support was by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. Blinded randomization.
Patients and results: 419 patients older tan 18 years with locally advanced thyroid carcinoma or well differentiate or poorly differentiate radioactive resistant metastatic thyroid carcinoma (papillary, follicular, Hurthle´s cell carcinoma and poorly differentiate), with progression over previous 14 months according to RECIST, with at least on measurable target lesion by CT or MR imaging, ECOG 0–2; normal kidney, medullar and liver function and TSH less than 0.5 mIU/L. Resistant radio-active iodine thyroid carcinoma was defined as the presence of at least 1 lesion without iodine uptake or patients with iodine uptake and progression over previous 16 months or progression after two cycles of radio-active iodine with less than 16 months of difference (lass cycle should be administered more 16 months before) or an total radioactive iodine of ?600 mCi. Patients who were treated before with target therapy, talidomide or systemic chemotherapy were excluded. Also patients with surgery or trauma 30 days before starting sorafenib, personal history of skin, cervical or bladder cancer, undifferentiated thyroid carcinoma, ulcers, active infection or bleeding in previous three months, bleeding history, tracheal, bronchial or esophageal infiltration, cardiomyopathy, uncontrolled high blood pressure, HIV infection, hepatitis, pregnancy or breast feeding and sorafenib allergy were excluded. Small chemotherapy doses for radio sensitization were allowed. Primary outcome was progression free survival (every 8 weeks) according to RECIST and secondary outcomes was overall survival, time to progression, rate of objective response (partial or complete), rate of disease control (partial, complete or stable) and response duration. Progression free survival was larger in the sorafenib group than in the placebo group (10.8 month vs5.8 months, HR 0.59 – IC 95% 0.45-0.76 p<0.0001). Sorafenib group had a higher side effects frequency (98·6 vs 87·6%).
Conclusion: Sorafenib significantly improves progression free survival compared with placebo in patients with radio-active iodine resistant progressive thyroid carcinoma. The difference is small. Side effects are frequent and quality of life and symptomatic improvement are not reported. This therapy must be used by experts and an individual assessment must be done and all available options must be used before consider the use of this treatment.

https://doi.org/10.53853/encr.2.3.93
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