Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer.
Summary of "Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer."
We evaluated the use of sorafenib to overcome resistance to aromatase inhibitors (AIs) in patients with metastatic breast cancer who had disease recurrence or progression while on AIs. We performed a multi-institution phase I/II study of sorafenib and anastrozole 1 mg daily in 35 postmenopausal females with hormone receptor positive metastatic breast cancer resistant to AIs. Primary objectives were to determine the dose of sorafenib in conjunction with anastrozole and the clinical benefit rate (CBR) (complete response [CR], partial response [PR], or stable disease [SD] ≥ 24 weeks). Secondary objectives were to determine toxicity and to evaluate if response was associated with change in number of circulating endothelial cells or circulating endothelial progenitor cells. Based on the phase I portion, sorafenib 400 mg twice daily was selected as the phase II dose. Among 35 patients, 7 had SD ≥ 24 weeks, 1 had PR ≥ 24 weeks, and 14 had progressive disease (PD) ≤ 24 weeks, corresponding to a CBR of 23%. The most common adverse events (all; Grade 3/4) were fatigue (66%; 17%), diarrhea (63%; 6%), nausea (60%; 9%), and hand-foot syndrome (57%; 34%). Dose reduction occurred in 77% of the patients and 31% came off study due to toxicity. The combination of sorafenib and anastrozole demonstrated a 23% CBR in patients with hormone receptor positive, AI-resistant metastatic breast cancer, which may be attributable to the restoration of sensitivity to AIs. Toxicities occurred frequently resulting in a high rate of discontinuation.
Affiliation
Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road, Washington, DC, 20057, USA, isaacsc@georgetown.edu.
Journal Details
This article was published in the following journal.
Name: Breast cancer research and treatment
ISSN: 1573-7217
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20976541
- DOI: http://dx.doi.org/10.1007/s10549-010-1226-z
Medical and Biotech [MESH] Definitions
Clinical Trial, Phase Iii
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques after phase II trials. A large enough group of patients is studied and closely monitored by physicians for adverse response to long-term exposure, over a period of about three years in either the United States or a foreign country.
Clinical Trials, Phase Iii As Topic
Comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.
Leukemia, Myeloid, Chronic-phase
The initial phase of chronic myeloid leukemia consisting of an relatively indolent period lasting from 4 to 7 years. Patients range from asymptomatic to those exhibiting ANEMIA; SPLENOMEGALY; and increased cell turnover. There are 5% or fewer blast cells in the blood and bone marrow in this phase.
Mifepristone
A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary CUSHING SYNDROME.
Clinical Trial, Phase Ii
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques based on several hundred volunteers, including a limited number of patients, and conducted over a period of about two years in either the United States or a foreign country.
PubMed Articles
The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase 3, rand...
BACKGROUNDS: The aim of this study was to assess the efficacy and safety of neoadjuvant anastrozole and radiation in postmenopausal breast cancer patients with hormone-receptor-positive tumors. In add...
Effect of simvastatin on the pharmacokinetics of anastrozole.
We have prospectively tested the effects of simvastatin on the pharmacokinetics of anastrozole and on estrogen concentrations in postmenopausal women with hormone receptor-positive breast cancer who w...
PURPOSE To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor-positive, metastatic breast cancer who have been render...
Background: Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patie...
Clinical Trials
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of bre...
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane or anastrozole may fight breast cancer by lowering the amount of estrogen the body makes....
This is a pivotal phase II, multicenter, open-label trial, designed to compare the efficacy of exemestane versus anastrozole as a first line treatment for advanced breast cancer. One hundr...
Anastrozole Reduced Proliferation and Progesterone Receptor Indexes in Short Term Hormone Therapy
Background: Identification of new biomarkers with potential predictive and prognostic role has contributed unequivocally to breast cancer treatment. Although traditionally endocrine thera...
The purpose of this study is to compare the rate of disease free survival (DFS) and distant disease free survival (DDFS) at 5 years in postmenopausal women with hormone receptor and lymph...
