ABSTRACT
INTRODUCTION/BACKGROUND: Targeted therapy has become the mainstay of treatment for mRCC. The efficacy of this therapy in the older population is poorly understood. PATIENTS AND METHODS: Data from patients with mRCC treated with first-line anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Patient characteristics, data on second-line therapy, and outcomes including treatment duration and overall survival, were evaluated using summary statistics and multivariate analysis. RESULTS: All patients (n = 1381) were treated with front-line targeted therapy; 144 (10%) were 75 years old or older. Six patients (4%) were favorable risk, 99 patients (69%) intermediate risk, and 39 patients (27%) poor risk according to Heng Journal of Clinical Oncology 2009 prognostic factors. The initial treatment for those ≥ 75 years of age was sunitinib (n = 98), sorafenib (n = 35), bevacizumab (n = 7), and AZD217 (n = 4). Twenty-three percent of older patients and 39% of the younger patients went on to receive second-line therapy (P < .0001). The overall response rate, median treatment duration, and overall survival for the older versus younger group were 18% versus 25% (P = .0975), 5.5 months versus 7.5 months (P = .1388), and 16.8 months versus 19.7 months (P = .3321), respectively. When adjusted for poor prognostic factors, age 75 years and older was not found to be associated with poorer overall survival (hazard ratio [HR], 1.002; 95% confidence interval [CI], 0.781-1.285) or shorter treatment duration (HR, 1.018; 95% CI, 0.827-1.252). The retrospective study design was the primary limitation. CONCLUSION: The use of advanced age as a selection criterion for targeted therapy requires further study, with data suggesting no clinically meaningful differences in overall response rate, treatment duration, and overall survival between older and younger age groups.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Molecular Targeted Therapy , Protein Kinase Inhibitors/therapeutic use , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Age Factors , Aged , Aged, 80 and over , Aging , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Bevacizumab , Carcinoma, Renal Cell/mortality , Databases, Factual , Female , Humans , Indoles/adverse effects , Indoles/therapeutic use , Kidney Neoplasms/mortality , Male , Niacinamide/adverse effects , Niacinamide/analogs & derivatives , Niacinamide/therapeutic use , Phenylurea Compounds/adverse effects , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/adverse effects , Pyrroles/adverse effects , Pyrroles/therapeutic use , Quinazolines/adverse effects , Quinazolines/therapeutic use , Retrospective Studies , Sorafenib , Sunitinib , Treatment OutcomeABSTRACT
Current understanding of mammalian circadian rhythms suggests that they are regulated by light targeting signaling pathways in the hypothalamic suprachiasmatic nuclei. Recently, investigators have identified the existence of extraretinal photoreceptors and a potential role for the skin in this regulatory process has been implied. We demonstrated that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human cultured keratinocytes. Low-dose ultraviolet B rays initially downregulate all circadian clock genes and then induce altered expression of the genes in keratinocyte cell cultures. Ultraviolet light targeting superficial layers of skin (keratinocytes) may therefore contribute to circadian rhythm modulation.
