Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: Guilherme Godoy*, Wan-fu Wu, Eunji Jo, Susan Hilsenbeck, Houston, TX, Dolores Lamb, New York, NY, Carolyn Smith, Seth Lerner, Houston, TX
Introduction: Recurrence rates of low/intermediate-risk bladder cancer are high and long-term follow-up is costly and invasive. Pre-clinical studies in bladder cancer cell lines and murine models suggest that targeting the estrogen receptor (ER) with selective ER modulators (SERM) may be an effective treatment strategy. We present herein the results of a phase II trial evaluating efficacy of tamoxifen, a prototypic SERM.
Methods: This single-arm, two-stage phase II study included adult subjects with low/intermediate-risk urothelial carcinoma of the bladder. The study employed the marker lesion design, and subjects received 20mg of oral tamoxifen daily for 12 weeks. Primary endpoint was reduction in size or elimination of the marker lesion, measured by the response evaluation criteria in solid tumors (RECIST) in combination with histopathologic findings. All additional tumors and normal bladder biopsy samples were evaluated for necrosis, scarring, fibrosis, and used for assessment of proliferation (Ki-67), apoptosis (cleaved PARP-1), and expression levels of ERα and ERβ by immunohistochemistry.
Results: The study enrolled 15 subjects, with 12 evaluable for the primary endpoint. Majority were men, with median age of 69 years (interquartile range, 61-77 years). Of these, 5 (42%) met the primary endpoint, including two (16.5%) with complete response (CR) and three (25%) with partial response (figure). One of the subjects with a CR had a residual papillary tumor, but biopsy revealed benign histology. The therapy was well tolerated with minimal toxicity. No grade 4 or 5 adverse events, but four (8.5%) grade 3 events were observed. Histology revealed no quantifiable fibrosis, scarring, or necrosis. Similarly, Ki-67 and cleaved PARP-1 markers were mostly negative across samples. ERβ was the predominantly expressed ER, with minimal ERα present. No significant differences were observed between the expression levels of the ERs in normal vs. tumor or pre vs. post-treatment samples. No gender-related associations could be made.
Conclusions: Oral tamoxifen effectively reduced the size or eliminated marker lesions in patients with low/intermediate-risk bladder cancer. The therapy was well tolerated. Clinical phase II/III trials are required to establish the benefit of tamoxifen in the management of bladder cancer.
Source of Funding: NIH - NCI grant K23CA160664 to GG