Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: A phase 1/2 clinical trial - Abstract

Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.


This phase 1/2 study assessed sunitinib combined with docetaxel (Taxotere) and prednisone in chemotherapy-naive metastatic, castration-resistant prostate cancer (mCRPC) patients.

To determine the recommended phase 2 dose (RP2D), 25 patients in four dose escalation cohorts received 3-week cycles of sunitinib (2 weeks on, 1 week off), docetaxel and prednisone, preceded by a 4-week sunitinib 50 mg/day lead in. RP2D was evaluated in 55 additional patients. The primary end point was prostate-specific antigen (PSA) response rate.

One phase 1 dose-limiting toxicity occurred (grade 3 hyponatremia). The RP2D was sunitinib 37.5 mg/day, docetaxel 75 mg/m(2) and prednisone 5 mg b.i.d. During phase 2, confirmed PSA responses occurred in 31 patients [56.4% (95% confidence interval 42.3-69.7)]. Median time to PSA progression was 9.8 months. Forty-one patients (75%) were treated >3 months, 12 (22%) completed the study (16 cycles) and 43 (78%) discontinued (36% for disease progression and 27% adverse events). The most frequent treatment-related grade 3/4 adverse events were neutropenia (53%; 15% febrile) and fatigue/asthenia (16%). Among 33 assessable patients, 14 (42.4%) had confirmed partial response. Median progression-free and overall survivals were 12.6 and 21.7 months, respectively.

This combination was moderately well tolerated, with promising response rate and survival benefit, justifying further investigation in mCRPC.

Written by:
Zurita AJ, George DJ, Shore ND, Liu G, Wilding G, Hutson TE, Kozloff M, Mathew P, Harmon CS, Wang SL, Chen I, Chow Maneval E, Logothetis CJ.   Are you the author?

Reference: Ann Oncol. 2011 Aug 5. Epub ahead of print.
doi: 10.1093/annonc/mdr349

PubMed Abstract
PMID: 21821830 Prostate Cancer Section