title: Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial.
abstract: BACKGROUND
  This phase 1/2 study assessed sunitinib combined with docetaxel (Taxotere) and prednisone in chemotherapy-naive metastatic, castration-resistant prostate cancer (mCRPC) patients.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  This combination was moderately well tolerated, with promising response rate and survival benefit, justifying further investigation in mCRPC.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston. Electronic address: azurita@mdanderson.org.
authors.forename: A J
authors.initials: AJ
authors.lastname: Zurita
authors.affiliation: Divisions of Medical Oncology and Urology, Duke University Medical Center, Durham.
authors.forename: D J
authors.initials: DJ
authors.lastname: George
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach.
authors.forename: N D
authors.initials: ND
authors.lastname: Shore
authors.affiliation: Hematology/Oncology Division, University of Wisconsin Carbone Cancer Center, Madison.
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.affiliation: Hematology/Oncology Division, University of Wisconsin Carbone Cancer Center, Madison.
authors.forename: G
authors.initials: G
authors.lastname: Wilding
authors.affiliation: Genitourinary Oncology Program, Baylor Sammons Cancer Center-Texas Oncology, P.A., Dallas.
authors.forename: T E
authors.initials: TE
authors.lastname: Hutson
authors.affiliation: Cancer Research Center, Ingalls Memorial Hospital, Harvey.
authors.forename: M
authors.initials: M
authors.lastname: Kozloff
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.
authors.forename: P
authors.initials: P
authors.lastname: Mathew
authors.affiliation: Departments of Translational Oncology.
authors.forename: C S
authors.initials: CS
authors.lastname: Harmon
authors.affiliation: Departments of Clinical Statistics.
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Departments of Clinical Development, Pfizer Oncology, La Jolla, USA.
authors.forename: I
authors.initials: I
authors.lastname: Chen
authors.affiliation: Departments of Clinical Development, Pfizer Oncology, La Jolla, USA.
authors.forename: E
authors.initials: E
authors.lastname: Chow Maneval
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.
authors.forename: C J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D000077210:Sunitinib; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D007211:Indoles; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D000077210:Sunitinib; D011241:Prednisone