A phase II study of lapatinib, a dual EGFR and HER-2 tyrosine kinase inhibitor, in patients with castration-resistant prostate cancer
| Autor: | Paul A. Godley, Karla Morris, W. Kimryn Rathmell, Dominic T. Moore, Daniel J. George, Gayle Grigson, Raj S. Pruthi, Jeffrey M. Crane, Eric Wallen, William Y. Kim, Catharine Watkins, Young E. Whang, Andrew J. Armstrong |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Oncology medicine.medical_specialty Receptor ErbB-2 medicine.drug_class Urology medicine.medical_treatment Phases of clinical research Adenocarcinoma Lapatinib Tyrosine-kinase inhibitor Targeted therapy Androgen deprivation therapy Prostate cancer Internal medicine medicine Humans Castration Prospective Studies Protein Kinase Inhibitors Survival rate Aged Neoplasm Staging Aged 80 and over business.industry Prostatic Neoplasms Middle Aged Prognosis medicine.disease ErbB Receptors Survival Rate Tolerability Quinazolines business Follow-Up Studies medicine.drug |
| Zdroj: | Urologic Oncology: Seminars and Original Investigations. 31:82-86 |
| ISSN: | 1078-1439 |
| DOI: | 10.1016/j.urolonc.2010.09.018 |
| Popis: | Objectives Epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer. Methods In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes. Results Twenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days. Conclusions Lapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents. |
| Databáze: | OpenAIRE |
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