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Sridhar SS , Hotte SJ , Chin JL , Hudes GR , Gregg R , Trachtenberg J , Wang LS , Tran-Thanh D , Pham NA , Tsao MS , Hedley D , Dancey JE , Moore MJ
A Multicenter Phase II Clinical Trial of Lapatinib (GW572016) in Hormonally Untreated Advanced Prostate Cancer
American Journal of Clinical Oncology-Cancer Clinical Trials. 2010 Dec;33(6) :609-613
PMID: ISI:000284825000015   
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Objectives: 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.
Sridhar, Srikala S. Hotte, Sebastien J. Chin, Joseph L. Hudes, Gary R. Gregg, Richard Trachtenberg, John Wang, Lisa Tran-Thanh, Danh Pham, Nhu-An Tsao, Ming-Sound Hedley, David Dancey, Janet E. Moore, Malcolm J. Nih ; nci [n01cm17107, n01cm62203] Supported by NIH grant to the Princess Margaret Hospital Consortium. NCI Contracts N01CM17107, N01CM62203. 26 Lippincott williams & wilkins; 530 walnut st, philadelphia, pa 19106-3621 usa 688br