Phase II trial of continuous treatment with sunitinib in patients with high-risk (BCG-refractory) non-muscle invasive bladder cancer
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Purpose Sunitinib is a vascular endothelial growth factor receptor (VEGFR) inhibitor with antitumor activity against bladder cancer. We hypothesized that treatment with sunitinib may decrease progression or recurrence in non-muscle invasive bladder cancer (NMIBC) refractory to intra-vesical BCG. Patients and Methods This is a single-arm phase II study of sunitinib in patients (pts) with NMIBC who progressed after BCG. Treatment included sunitinib 37.5 g daily for 12 weeks followed by 12± 2-week cystoscopy and surveillance for one year. The primary endpoint was the complete response rate at 12 months. Secondary endpoints included recurrence free survival (RFS), progression free survival (PFS), overall survival (OS), and safety of sunitinib. Correlative studies on effects of sunitinib on myeloid derived suppressor cells (MDSC) and humoral immune responses were also performed. This trial was registered on ClinicalTrials.gov, number NCT01118351. Results Between June 2011 and September 2011, 15/19 pts. completed 12 weeks of therapy. The remaining 4 pts. had treatment related adverse events leading to discontinuation of sunitinib with one patient withdrawing consent. On the 12-week cystoscopy, 44% (8/18) of the pts. showed remission, 50% (9/18) progression and 1/18 recurrence. Overall, 22% (4/18) of pts. remained free of progression for >12 months. Grade (G) 4 toxicities were noted in 2 pts. (anemia and thrombocytopenia) while G3 were noted in 58%. Sunitinib resulted in reversal of MDSC mediated immunosuppression. Conclusions In NMIBC refractory to BCG, treatment with sunitinib was safe but not associated with improved clinical outcomes. The immune effects of sunitinib deserve further investigation.
KeywordsSunitinib Non-muscle invasive bladder cancer BCG-refractory Angiogenesis MDSC
HZ contributed to the data acquisition, drafting and final revision of the manuscript. MCM participated in data acquisition and final revision of the manuscript. PCB participated in data acquisition and final revision of the manuscript. AJS participated in data acquisition and final revision of the manuscript. SCC participated in data acquisition and final revision of the manuscript. RD participated in data acquisition and final revision of the manuscript. JAG contributed to the conception and coordination of the study, data acquisition, drafting and final revision of the manuscript. All authors read and approved the manuscript.
The work was supported by the Pfizer Inc.
Compliance with ethical standards
Conflicts of interest
HZ declares that he has no conflict of interest. MCM declares that he has no conflict of interest. PCB declares that he has no conflict of interest. AJS declares that he has no conflict of interest. SCC declares that he has no conflict of interest. AF declares that he has no conflict of interest. RD has served as a consultant for Astra Zeneca, Janssen, Pfizer, Lilly and Astellas. The other authors declare no competing interests directly related to this manuscript. JAG has honoraria from Bayer, Sanofi, Pfizer, Genentech, Janssen, Eisai and Exelixis.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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