title: A phase II study of insulin-like growth factor receptor inhibition with             nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate             cancer.
abstract: Insulin-like growth factor (IGF)-mediated signaling is a newly recognized             clinical target in prostate cancer, and it is hypothesized that blockade of the             IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In             this study the efficacy of nordihydroguaiaretic acid (NDGA), a small molecule             inhibitor of the IGF-1R, was prospectively evaluated in patients with non-metastatic             hormone-sensitive prostate cancer (HSPC). Eligible patients had non-metastatic             HSPC with a rising prostate-specific antigen (PSA) and a normal testosterone level.             NDGA 2000 mg was given orally daily in 28 day cycles and treatment continued until             PSA progression or toxicity. Accrual was stopped early after a pre-planned interim             analysis showed no significant PSA declines after 3 cycles of treatment among             the first 12 patients enrolled. Median time on treatment was 9 cycles (range 2-19)             for 11 patients now off study; 1 patient continues to receive therapy and has             been on study for 29 months. Seven patients experienced non-sustained declines             in PSA ranging from 1.9 to 15.8% of baseline. PSADT lengthened by a median of             1.4 months for all evaluable patients when compared to pretreatment PSADT (range             -6.1 to +19.8 months). Grade 3 events were rare and included nausea/vomiting,             syncope due to dehydration, and elevated liver function tests in 1 patient, and             cognitive disturbance in another patient. NDGA therapy lengthens median PSADT             but does not induce significant PSA declines. Further study may require a placebo-control             to determine if changes in PSADT are drug related.
authors.affiliation: Genitourinary Medical Oncology Program, Biostatistics and Computational Biology Core, Helen Diller Family Comprehensive Cancer Center, Department of Bioengineering and Therapeutic Sciences, Box 1711, 1600 Divisadaro Street, University of California, San Francisco, San Francisco, CA 94115-1711, USA. terence.friedlander@ucsf.edu
authors.forename: Terence W
authors.initials: TW
authors.lastname: Friedlander
authors.forename: Vivian K
authors.initials: VK
authors.lastname: Weinberg
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Joanna T
authors.initials: JT
authors.lastname: Mi
authors.forename: Carl G
authors.initials: CG
authors.lastname: Formaker
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Harzstark
authors.forename: Amy M
authors.initials: AM
authors.lastname: Lin
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fong
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009637:Masoprocol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D017451:Receptors, Somatomedin; D009637:Masoprocol; D017430:Prostate-Specific Antigen