Circulating tumor cell kinetics in mRCC patients treated with sunitinib

Abstract

Background: Detection of circulating tumor cells (CTCs) in renal cell carcinoma (RCC) is limited by inconsistent expression of epithelial cell adhesion molecule. We have previously detected CTCs using microfilter devices that exploit size differences between larger epithelial tumor and smaller non-tumor blood cells. Methods: Treatment naive pts with clear cell metastatic RCC (mRCC) were enrolled on a prospective phase II trial of intermittent sunitinib. Peripheral blood samples were collected at baseline, day 28 of cycles 1, 2, 4, and after the 8-week off-treatment period. Peripheral blood was diluted 1:1 with PBS and 1% formalin. Cells were captured with microfilters, stained with pan cytokeratin (CK) and CD45, conjugated with Alexa Fluor (AF) 594 and AF 488. Microfilters were cover-slipped with a DAPI containing medium for nuclear visualization. CTCs were identified as large CK+/CD45- events. Results: Pt characteristics (n=17) included 13 male/4 female; median age 65 years; median performance status KPS 90%; 100% prior nephrectomy. By Heng criteria, 4 pts were favorable, 12 intermediate and 1 poor risk. Site of metastases included lungs (59%), bone (41%) and lymph nodes (35%). Baseline CTCs (35 total samples collected) were detectable in at least one sample in 9 patients (53%), with a median CTC count of 6 (range, 1-31/ml); overall median CTC count was 1 CTC/ml including undetectable patients at baseline. Intrapatient variability was observed with the maximum intrapatient range of 4 to 58 CTCs/ml. After cycle 1 of sunitinib, median CTCs increased to 23 cells/ml (range, 0-94). Median CTCs after cycle 2 was 2 cells/ml (range, 0-322) and cycle 4 was 4.5 cells/ml (range, 0-500). After the 8 week off-treatment period, a median of 3.5 CTCs/ml (range, 0-242) were detected. In 6 patients with undetectable CTCs at baseline, CTCs were detected during the first 2 cycles of treatment, and in 4 of these patients, they declined or became undetectable by the last sampling period. Conclusions: A high rate of CTC detection is demonstrated using micro-filters in mRCC. CTC levels tend to increase during the first few weeks of treatment with sunitinib, and then decline with continued sunitinib and after sunitinib is held.

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