title: Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer.
abstract: OBJECTIVE
  The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen.
  
  
  RESULTS
  Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P = .0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40% of patients receiving TASQ versus 10% receiving placebo; deep vein thrombosis (4% v 0%) was more common in the TASQ arm.
  
  
  CONCLUSIONS
  TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY 14263-0001, USA. roberto.pili@roswellpark.org
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Michael
authors.initials: M
authors.lastname: Häggman
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gingrich
authors.forename: Vasileios J
authors.initials: VJ
authors.lastname: Assikis
authors.forename: Anders
authors.initials: A
authors.lastname: Björk
authors.forename: Orjan
authors.initials: O
authors.lastname: Nordle
authors.forename: Goran
authors.initials: G
authors.lastname: Forsberg
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D040502:Calgranulin B / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009919:Orchiectomy; D010919:Placebos; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011804:Quinolines / Q000627:therapeutic use*; D015363:Quinolones
chemical_list: D000970:Antineoplastic Agents; D040502:Calgranulin B; D010919:Placebos; D011804:Quinolines; D015363:Quinolones; C516109:tasquinimod