Phase II Trial of Sunitinib for the Therapy of Progressive Metastatic Castration- Refractory Prostate Cancer After Previous Docetaxel Chemotherapy Guru Sonpavde 1 Thomas E. Hutson 1 William R. Berry 2 Kristi A. Boehm 3 Lina Asmar 3 1 Texas Oncology and Baylor Sammons Cancer Center, Dallas 2 Cancer Centers of North Carolina, Raleigh 3 US Oncology Research, Houston, Texas Clinical Genitourinary Cancer, Vol. 6, No. 2, 134-137, 2008 Keywords: Prostate-specific antigen, Targeted therapy, Tyrosine kinase inhibitors DOI: 10.3816/CGC.2008.n.023 Submitted: Oct 30, 2007; Revised: Dec 18, 2007; Accepted: Feb 25, 2008 Address for correspondence: Guru Sonpavde, MD Genitourinary Oncology Program Texas Oncology, PA, US Oncology Research 501 Medical Center Blvd Webster, TX 77598 Fax: 281-332-8429 E-mail: guru.sonpavde@usoncology.com Rationale and Background Docetaxel-based chemotherapy has extended survival for patients with meta- static castration-resistant prostate cancer (CRPC). 1,2 However, the median survival for patients with metastatic CRPC receiving docetaxel is approximately 18 months with a median progression-free survival (PFS) of only 6 months. After failure of docetaxel, effective options are lacking, and novel, tolerable, and convenient thera- peutic modalities are needed. 3 Sunitinib is an orally administered, small-molecule, multitargeted kinase inhibitor with selectivity for vascular endothelial growth fac- tor (VEGF) receptor (VEGFR) 1, 2, and 3; platelet-derived growth factor (PDGF) receptor (PDGFR)–α and PDGFR-β; Flt3; Kit; and RET. 4,5 It is multinationally approved for renal cell cancer and gastrointestinal stromal tumors. 6,7 We present the rationale and design to evaluate sunitinib for CRPC. Several major targets of sunitinib are overexpressed in prostate cancer. The elevation of urinary VEGF might be a predictor of disease progression, and urinary levels of VEGF reflect the therapeutic effect of radical prostatectomy but not that of hormonal therapy. 8,9 Increased expression of VEGF-C and VEGFR-3 play a role in prostate cancer progression and in metastasis to re- gional lymph nodes. 10 VEGFR-1 and, to a limited extent, VEGFR-2 were activated (ie, phosphorylation of immunoprecipitated VEGFR) in early-stage specimens, whereas VEGFR-2 and VEGFR-3 were activated in advanced- stage specimens. 11 Microvessel density determined by immunohistochemistry for CD34 was increased in an androgen-independent subline compared with androgen-dependent LNCaP cells. 12 Plasma levels of VEGF increased incre- mentally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. 13 Higher preoperative VEGF Effective options are lacking for progressive castration-refractory prostate cancer (CRPC) after conventional chemotherapy. Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor that is approved multinationally for renal cell carcinoma and gastrointes- tinal stromal tumors. A phase II trial was conducted to examine the efficacy and toxicities of sunitinib in metastatic CRPC progressing after 1-2 previous chemotherapy regimens including docetaxel. The primary objective was clinical progression-free survival (PFS) with a 12-week PFS ≥ 30% assumed to be of interest. Secondary objectives included prostate-specific antigen (PSA) response, modulation of PSA kinetics, objective response, quality of life, pain, survival, and toxicities. Sunitinib 50 mg daily was administered orally on days 1-28 of each 6-week cycle. Patients were treated to a maximum of 8 cycles or until clinically progressive disease or intolerable toxicity. Abstract Current Trial Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1558-7673, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400. 134 • Clinical Genitourinary Cancer September 2008 *Please note that this study is closed to enrollment and is no longer accruing patients.