RESUMEN
INTRODUCTION: GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES: To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. METHODS: Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/terapia , Terapia Combinada , Diarrea/inducido químicamente , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Fatiga/inducido químicamente , Femenino , Síndrome Mano-Pie/etiología , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Terapia Recuperativa , Índice de Severidad de la Enfermedad , Sorafenib , España , Resultado del TratamientoRESUMEN
Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Ciclooxigenasa 2/genética , Indoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Polimorfismo de Nucleótido Simple/genética , Pirroles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Humanos , Indoles/farmacología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos Genéticos , Análisis Multivariante , Pirroles/farmacología , Sunitinib , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: A previous study of cancer-related neuropathic pain (NP) found that a 10-fold increase in pregabalin (PGB) use increased patients' satisfaction with treatment. Further research of PGB vs. non-pregabalin (non-PGB) treatment was carried out to assess if the use of more specific NP-targeting drugs, such as PGB, in combined therapy, in patients with cancer-related NP, provides better health outcomes. PATIENTS AND METHODS: Post hoc analysis of PGB- vs. non- PGB-treated patients in a 2-month epidemiological, prospective, multicentre study to assess NP prevalence and management in cancer pain patients visiting radiotherapy oncologic units. Patients undertook the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), the Medical Outcomes Sleep Scale (MOS-Sleep) and the short form (SF-12) Health Survey. RESULTS: A total of 273 patients with no previous PGB treatment: 162 were treated with PGB polytherapy and 111 with other treatments. At 8 weeks, satisfaction with treatment was 92.6% (PGB) vs. 78.9% (non-PGB), p=0.0024, and benzodiazepine use 37.8% (non-PGB) vs. 19.8% (PGB), p=0.0009. The decreases in BPI total pain intensity and total interference with activities and in MOS overall sleep problems index were significantly larger in the PGB group. CONCLUSIONS: The addition of more specific NP-targeting drugs to usual treatment, such as PGB, in NP cancer patients provides more satisfaction with treatment and better outcomes in terms of pain intensity, interference with activities and sleep than treatments without specific NP-targeting drugs. Anxiolytic profile of PGB could allow for less use of benzodiazepines.