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    ABSTRACT: Background Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective and heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery. Objective To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC). Design, setting, and participants This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible. Intervention Patients received axitinib 5 mg for up to 12 wk. Axitinib was continued until 36 h prior to surgery. Patient underwent partial or radical nephrectomy after axitinib therapy. Outcome measurements and statistical analysis The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST). Results and limitations A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers. Conclusions Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC. Patient summary In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use. Trial registration This clinical trial was registered with clinicaltrials.gov (NCT01263769).
    European Urology 04/2014; 66(5). DOI:10.1016/j.eururo.2014.01.035 · 12.48 Impact Factor
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    ABSTRACT: A 72-year-old man presenting with a 14-cm left renal mass, an inferior vena cava (IVC) tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Because of metastases and the extent of the tumor thrombus, sunitinib was administered, which resulted in a marked reduction in the tumor thrombus (from level III to level II after 11 weeks of treatment). Ultrasonography, preceding computed tomography, showed a slight shrinkage of the tumor thrombus level in the first 2 weeks. Therefore, ultrasound may be advantageous to monitor the IVC tumor thrombus level during the early phase of targeted therapy.
    Journal of Medical Ultrasonics 10/2013; 40(4). DOI:10.1007/s10396-013-0448-1 · 0.74 Impact Factor
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    ABSTRACT: Objective: The aim of this study is to identify the pre-operative prognostic factors and create a risk stratification model for patients with renal cell carcinoma with extension into the renal vein or inferior vena cava. Methods: The study cohort included 61 patients with renal cell carcinoma extending into the renal vein or inferior vena cava that underwent operations between 1993 and 2012. Cancer-specific survival rates were estimated, and univariate and multivariate analyses were carried out to determine the prognostic factors. A simple risk stratification model was developed for these patients. Results: The median follow-up period of the current patient cohort was 33.7 months. Their 1, 3 and 5-year cancer-specific survival were 89, 70 and 65%, respectively. On multivariate analysis, the level of tumor thrombus extension (extension into the supradiaphragm), presence of distant metastasis and elevation of lactate dehydrogenase and C-reactive protein were independent negative prognostic factors for cancer-specific survival. Cancer-specific survival rates were clearly discriminated by the stratification according to the scoring model (P < 0.001). The concordance index of the new model was 0.80. Conclusions: We demonstrated a simple risk stratification model with four pre-operative independent prognostic factors for patients with renal cell carcinoma with venous involvement. This may be a useful decision-making model in the management of such patients.
    Japanese Journal of Clinical Oncology 05/2014; 44(8). DOI:10.1093/jjco/hyu072 · 1.75 Impact Factor