title: A multicenter phase II clinical trial of lapatinib (GW572016) in hormonally untreated advanced prostate cancer.
abstract: OBJECTIVE
  Lapatinib (GW572016) is a selective and potent dual tyrosine kinase inhibitor of the epidermal growth factor 1 (EGFR) and 2 (HER2), approved in the treatment of HER2 positive breast cancer. Since EGFR and HER2 overexpression has also been seen in prostate cancer and appears to correlate with a worse clinical outcome, Lapatinib may represent a novel therapeutic strategy in prostate cancer. This Phase II multicenter clinical trial is the first to evaluate Lapatinib in early stage, hormonally untreated recurrent or metastatic prostate cancer.
  
  
  METHODS
  Eligible patients received lapatinib 1500 mg PO daily until progression. The primary end point was prostate specific antigen (PSA) response. Archival tumor tissue was collected for EGFR and HER2 analysis.
  
  
  RESULTS
  A total of 23 patients, median age 67, ECOG PS 0-2, mean baseline PSA 7.5, were evaluable for response. In total, 125 cycles were administered. The most frequent adverse events were lymphopenia, fatigue, rash, dyspepsia, and diarrhea. Grade 3+ increased alanine aminotransferase (ALT) was reported in 2 patients, and grade 4 blurry vision in 1 patient. No PSA responses were seen. Median time to progression (TTP) was 4.6 months and 6 months progression-free estimate was 44.5%.
  
  
  CONCLUSIONS
  Lapatinib was well tolerated but like other EGFR- and HER2-targeted agents in advanced HRPC failed to show significant antitumor activity even in this very early stage hormonally untreated population.
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada. srikala.sridhar@uhn.on.ca
authors.forename: Srikala S
authors.initials: SS
authors.lastname: Sridhar
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Chin
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: Richard
authors.initials: R
authors.lastname: Gregg
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Danh
authors.initials: D
authors.lastname: Tran-Thanh
authors.forename: Nhu-An
authors.initials: NA
authors.lastname: Pham
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology*; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D016037:Single-Blind Method; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D011799:Quinazolines; D000077341:Lapatinib; D017430:Prostate-Specific Antigen