RESUMO
Hematological and gastrointestinal toxicities are common among patients treated with cyclophosphamide and doxorubicin for breast cancer. To examine whether single-nucleotide polymorphisms (SNPs) in key pharmacokinetic genes were associated with risk of hematological or gastrointestinal toxicity, we analyzed 78 SNPs in ABCB1, ABCC1 and ALDH1A1 in 882 breast cancer patients enrolled in the SWOG trial S0221 and treated with cyclophosphamide and doxorubicin. A two-SNP haplotype in ALDH1A1 was associated with an increased risk of grade 3 and 4 hematological toxicity (odds ratio=1.44, 95% confidence interval=1.16-1.78), which remained significant after correction for multiple comparisons. In addition, four SNPs in ABCC1 were associated with gastrointestinal toxicity. Our findings provide evidence that SNPs in pharmacokinetic genes may have an impact on the development of chemotherapy-related toxicities. This is a necessary first step toward building a clinical tool that will help assess risk of adverse outcomes before undergoing chemotherapy.
Assuntos
Aldeído Desidrogenase/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Família Aldeído Desidrogenase 1 , Neoplasias da Mama/genética , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Retinal DesidrogenaseAssuntos
Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Hipotireoidismo/induzido quimicamente , Piridinas/efeitos adversos , Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma de Células das Ilhotas Pancreáticas/complicações , Carcinoma de Células das Ilhotas Pancreáticas/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Niacinamida/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Compostos de Fenilureia , Piridinas/uso terapêutico , SorafenibeRESUMO
Carcinoid tumors and islet cell neoplasms are neuroendocrine neoplasms with indolent patterns of growth and association with bizarre hormone syndromes. These tumors behave in a relatively protracted and predictable manner, which allows for multiple therapeutic options. Even in the presence of hepatic metastases, the standard of treatment for neuroendocrine malignancy is surgery, either with curative intent or for tumor cytoreduction, i.e., resection of 90% or more of the tumor volume. Image-guided ablation, as either an adjunct to surgery or a primary treatment modality, can be used to treat neuroendocrine cancer metastatic to the liver. Image-guided ablative techniques, including radiofrequency ablation, alcohol injection, and cryoablation, can be used in selected patients to debulk hepatic tumors and improve patient symptoms. Although long-term follow-up data are not available, the surgical literature indicates that significant ablative debulking may improve patient survival. In this review, we discuss metastatic neuroendocrine disease and its treatment options, especially image-guided ablative techniques.