Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment of patients with hormone receptor-negative metastatic breast cancer Journal Article
| Authors: | Gucalp, A.; Sparano, J. A.; Caravelli, J.; Santamauro, J.; Patil, S.; Abbruzzi, A.; Pellegrino, C.; Bromberg, J.; Dang, C.; Theodoulou, M.; Massague, J.; Norton, L.; Hudis, C.; Traina, T. A. |
| Article Title: | Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment of patients with hormone receptor-negative metastatic breast cancer |
| Abstract: | SRC activation is associated with cell migration, proliferation, and metastasis. Saracatinib is an oral tyrosine kinase inhibitor (TKI) selective for SRC. We performed this trial to evaluate the efficacy and safety of saracatinib monotherapy in patients with estrogen receptor (ER)(-) and progesterone receptor (PR)(-) metastatic breast cancer (MBC). Patients who had undergone ≤ 1 previous chemotherapy regimen for measurable ER(-) and PR(-) MBC received saracatinib 175 mg orally daily. The primary endpoint was disease control defined as complete response (CR) + partial response (PR) + stable disease (SD) > 6 months. Secondary endpoints included toxicity and progression-free survival (PFS). Levels of circulating tumor cells (CTCs) in response to therapy were measured over time. Nine patients were treated on study. After a median of 2 cycles (range 1-3), no patient had achieved CR, PR, or SD >6 months. The median time to treatment failure was 82 days (12-109 days).The majority (89%) of patients discontinued saracatinib because of disease progression. One patient acquired potentially treatment-related grade 4 hypoxia with interstitial infiltrates and was removed from the study. Common adverse events included fatigue, elevated liver enzymes, nausea, hyponatremia, dyspnea, cough, and adrenal insufficiency. These efficacy results were not sufficiently promising to justify continued accrual to this study. Based on this series, saracatinib does not appear to have significant single-agent activity for the treatment of patients with ER(-)/PR(-) MBC. Copyright © 2011. Published by Elsevier Inc. |
| Keywords: | adult; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; clinical trial; antineoplastic agents; united states; disease free survival; antineoplastic agent; metabolism; metastasis; phase 2 clinical trial; protein kinase inhibitor; pathology; protein tyrosine kinase; breast neoplasms; protein kinase inhibitors; drug antagonism; multicenter study; breast tumor; neoplasm metastasis; new york city; benzodioxoles; receptors, estrogen; receptors, progesterone; protein-tyrosine kinases; estrogen receptor; progesterone receptor; administration, oral; quinazolines; quinazoline derivative; oral drug administration; 1,3 benzodioxole derivative; n (5 chloro 1,3 benzodioxol 4 yl) 7 (2 (4 methylpiperazin 1 yl)ethoxy) 5 (tetrahydro 2h pyran 4 yloxy)quinazolin 4 amine; n-(5-chloro-1,3-benzodioxol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)-5-(tetrahydro-2h-pyran-4-yloxy)quinazolin-4-amine |
| Journal Title: | Clinical Breast Cancer |
| Volume: | 11 |
| Issue: | 5 |
| ISSN: | 1526-8209 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2011-01-01 |
| Start Page: | 306 |
| End Page: | 311 |
| Language: | English |
| PUBMED: | 21729667 |
| PROVIDER: | scopus |
| PMCID: | PMC3222913 |
| DOI: | 10.1016/j.clbc.2011.03.021 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2012" - "Source: Scopus" |
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