Dados do Trabalho

Título

Chemotherapy in patients with colon and rectal cancer who present DPD deficiency: A systematic review of the adequate dosage of 5-Flurouracil when indicated

Introdução

There is a very important role of neoadjuvant chemotherapy in patients with locally advanced colon cancer (LACC), and 5-Flurouracil (5-FU) and its pro-drug capecitabine are widely used agents in the management of these malignancies. Though 5-FU-based treatment is usually well tolerated, approximately 31–34% of cancer patients develop grade 3 or 4 toxicities, which pharmacogenetic studies associated that part of those effects were due to dihydropyrimidine dehydrogenase (DPD) deficiency, which is responsible for catabolism of 80–85% of administered 5-FU.

Objetivo

Demonstrate the possibility of therapy with 5-FU in patients with DPD deficiency and adequate dosage

Método

This systematic review was carried out according to a predefined protocol, studies published in the last 10 years were identified through an electronic search of the US National Library of Medicine (MEDLINE). The search strategy used: (colon OR rectal OR colorectal) AND (cancer OR carcinoma) AND (DPD deficiency) AND (chemotherapy OR therapy). The title and abstract of each study was examined for relevance with full text being obtained for all potentially relevant studies. Studies were included regardless of design, with both trials and observational studies being eligible for inclusion.

Resultados

Studies demonstrated that patients present different levels of DPD deficiency and the individualized chemotherapy dosage based on the level of deficiency provided by DPYD genotype it's crucial to individualize the treatment dosage, since the role of chemotherapy is unquestionable on colon and rectal cancer as a neoadjuvant, adjuvant or palliative treatment. For the treatment it is recommended to reduce the initial FU dose (0.8%-5% of original dose) according to DPD status and increase conform tolerance. Pharmacokinetic analyses showed that the area under the concentration-time curve (AUC) and half-life of 5-fluorouracil were respectively tenfold and fourfold higher than control values of patients receiving capecitabine 850 mg/m2. Studies experimented administrating once every 5 days and when extrapolating from this dosing schedule to twice daily, the AUC of 5-fluorouracil was comparable to controls.

Conclusão

DPD deficiency is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity, however studies have shown that it's possible to provide adjusted dosage chemotherapy to patients with DPD deficiency and even in low dosage there’s oncological benefit for those patients.