ABSTRACT
AIM: The multi-tyrosine kinase inhibitor pazopanib prolongs progression-free survival (PFS) versus placebo in treatment-naive and cytokine-refractory metastatic clear-cell renal cell carcinoma (ccRCC). Outcomes and safety data with pazopanib after targeted therapy (TT) are limited. METHODS: We retrospectively evaluated records of consecutive patients with metastatic ccRCC who had progressive disease (PD) after TT and received pazopanib from November 2009 through November 2011. Tumour response was assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumours (RECIST). PFS and overall survival (OS) were estimated by Kaplan-Meier methods. RESULTS: Ninety-three patients were identified. Median number of prior TTs was 2 (range, 1-5). There were 68 events (PD or death). Among 85 evaluable patients, 13 (15%) had a partial response. Median PFS was 6.5 months (95% CI: 4.5-9.7); median OS was 18.1 months (95% CI: 10.26-NA). Common adverse events (AEs) included fatigue (44%), elevated transaminases (35%), diarrhoea (30%), hypothyroidism (18%), nausea/vomiting (17%), anorexia (14%) and hypertension exacerbation (14%); 91% of AEs were grade 1/2. Eleven patients (12%) discontinued therapy due to AEs. There were no treatment-related deaths. CONCLUDING STATEMENT: Pazopanib demonstrated efficacy in patients with metastatic ccRCC after PD with other TTs. Toxicity overall was mild/moderate and manageable.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Pyrimidines/therapeutic use , Sulfonamides/therapeutic use , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Carcinoma, Renal Cell/pathology , Disease Progression , Disease-Free Survival , Female , Humans , Indazoles , Kidney Neoplasms/pathology , Male , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/adverse effects , Retrospective Studies , Sulfonamides/adverse effectsABSTRACT
A series of articles has recently appeared in which implications of second-order cybernetics for the practice of family therapy have been discussed. In this article, we attempt to advance the discussion by addressing ideas that we think have not been adequately emphasized thus far. Specifically proposed are ideas about conditions that might facilitate the emergence of consciously pragmatic strategy informed by the kind of systemic wisdom that delicately balances natural systems without the benefit of human planning. It is argued that a shift in the personal habits of knowing and acting that typically organize individual human experience is required. After attempting to specify what this shift might involve, implications of these ideas for the practice of family therapy and for human action in general are discussed.