The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit. and A. Paulík, J. Grim, S. Filip
Cílená léčba je indikována u řady solidních nádorů samostatně nebo v kombinaci s chemoterapií, hormonální léčbou či radioterapií. Její uvedení do praxe přineslo zlepšení prognózy mnoha nádorových onemocnění, ale také některé méně obvyklé nežádoucí účinky. Cílená terapie může zvyšovat hematologickou toxicitu chemoterapie a způsobovat narušení ochranných bariér nebo přímo inhibovat funkce imunitních buněk. Rutinní profylaktická antiinfekční terapie se v současnosti u pacientů léčených cílenou léčbou pro solidní nádor nedoporučuje. Některé cílené léky predisponují ke specifickým infekčním komplikacím., Targeted therapy is indicated for many types of solid malignancies, either in monotherapy or in combination with chemotherapy, hormonal therapy, or radiotherapy. The incorporation of targeted drugs into clinical algorithms has improved the prognosis of many cancers but also increased the risk of some less common adverse effects. Targeted therapy may increase haematological toxicity of chemotherapy and cause disruption of protective barriers or directly inhibit the function of immune cells. Routine prophylactic anti-infective therapy in patients treated with current targeted therapies for solid tumors is not recommended. Some targeted drugs, however, may predispose to specific infectious complications., Tomáš Büchler, and Literatura