RESUMEN
5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.
Asunto(s)
Capecitabina/uso terapéutico , Dihidrouracilo Deshidrogenasa (NADP)/genética , Fluorouracilo/uso terapéutico , Técnicas de Genotipaje/normas , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Selección de Paciente , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To provide guidance for the management of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in daily practice. METHODS: Nominal group and Delphi techniques were used. A steering committee of seven experts analyzed the current management of RAS wt mCRC, through which they identified controversies, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a group of 30 experts (the expert panel) was selected to test agreement with the statements, through two Delphi rounds. The following response categories were established in both rounds: 1 = totally agree, 2 = basically agree, 3 = basically disagree, 4 = totally disagree. Agreement was defined if ≥ 75% of answers were in categories 1 and 2 (consensus with the agreement) or 3 and 4 (consensus with the disagreement). RESULTS: Overall, 71 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) tumor location; (3) triplets; (4) maintenance; (5) second-line and beyond treatments; (6) Rechallenge and liquid biopsy. After the two Delphi rounds, only six statements maintained a lack of clear consensus. CONCLUSIONS: This document aims to describe the expert's attitude when dealing with several common clinical questions regarding patients with RAS wt mCRC.
Asunto(s)
Comités Consultivos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Consenso , Técnica Delphi , Genes ras/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Colon Ascendente/patología , Colon Transverso/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias Colorrectales/patología , Receptores ErbB/antagonistas & inhibidores , Fluorouracilo/uso terapéutico , Genotipo , Humanos , Leucovorina/uso terapéutico , Biopsia Líquida , Quimioterapia de Mantención/métodos , Compuestos Organoplatinos/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , RetratamientoRESUMEN
Localized rectal adenocarcinoma is a heterogeneous disease and current treatment recommendations are based on a preoperative multidisciplinary evaluation. High-resolution magnetic resonance imaging and endoscopic ultrasound are complementary to do a locoregional accurate staging. Surgery remains the mainstay of treatment and preoperative therapies with chemoradiation (CRT) or short-course radiation (SCRT) must be considered in more locally advanced cases. Novel strategies with induction chemotherapy alone or preceding or after CRT (SCRT) and surgery are in development.