title: Eastern Cooperative Oncology Group Phase II Trial of lapatinib in men with biochemically relapsed, androgen dependent prostate cancer.
abstract: OBJECTIVE
  Activation of the epidermal growth factor pathway is important in prostate cancer development and the transcription of androgen receptor regulated genes. This study evaluated the potential activity of lapatinib in men with biochemically-relapsed androgen-dependent (stage D0) prostate cancer.
  
  
  METHODS
  Patients with a rising PSA after primary therapy for prostate cancer were enrolled. A PSA doubling time (PSADT) <12 months was required. Lapatinib was administered at 1,500 mg orally daily. Outcome measures were changes in PSA kinetics. Primary tumor blocks were obtained and assessed for EGFR expression, EGFR Q787Q polymorphism, and Kras 38 mutational status.
  
  
  RESULTS
  Forty-nine patients were enrolled (14 ineligible), resulting in 35 patients for analysis. No PSA response was observed; best response was stable disease (n = 28, 80.0%). Pretreatment average slope was 0.19 log (PSA)/month (PSADT = 3.70 months), in contrast to on-treatment average slope of 0.13 log (PSA)/month (PSADT = 5.44 months) using linear mixed effects models (P = 0.006). Median progression-free survival (PFS) was 17.4 months for the high EGFR group and 6.0 months for the low EGFR group (P = 0.50). Patients with Kras 38 mutation had shorter PFS than those without Kras 38 mutation (P = 0.09).
  
  
  CONCLUSIONS
  Although no PSA responses (primary endpoint) was observed, lapatinib may have biologic activity in men with stage D0 prostate cancer as evidenced by a decrease in PSA slope in this non-randomized study. Additional trials assessing the role of EGFR overexpression and Kras wild type status in prostate cancer should be investigated.
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA. gxl@medicine.wisc.edu
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Jill
authors.initials: J
authors.lastname: Kolesar
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Robert
authors.initials: R
authors.lastname: Dipaola
authors.forename: Michael
authors.initials: M
authors.lastname: Pins
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
authors.forename: Mark
authors.initials: M
authors.lastname: Stein
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Bubley
authors.forename: George
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use*; D018631:ras Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000077341:Lapatinib; D066246:ErbB Receptors; D017430:Prostate-Specific Antigen; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins