Journal article
Phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR plus ) metastatic breast cancer
Investigational new drugs, Vol.35(1), pp.87-94
02/01/2017
DOI: 10.1007/s10637-016-0403-2
PMCID: PMC5590750
PMID: 27826831
Abstract
Introduction Suppressing both androgens and estrogens may circumvent hormone receptor resistance in breast cancer by reducing androgen receptor stimulation. Selective inhibition of the 17, 20-lyase enzyme by orteronel leads to decreased androgen production in men and would be anticipated to reduce estrogen and androgen production in women. Thus, we conducted a phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. Methods The primary objective was to identify the recommended phase 2 dose (R2PD) of orteronel in women; escalation was via standard 3 + 3 design. The initial dose was 300 mg BID and escalated to 400 mg BID. Cycle length was 28 days. Enrolled patients had HR+ metastatic breast cancer and were evaluated every 8 weeks for disease progression. Results Eight heavily pre-treated women enrolled [ median age: 57 yo (range 47-73)]. Four received 300 mg BID at dose level 1; 4 received 400 mg BID at dose level 2. No dose limiting toxicities (DLTs) were observed. Adverse events (AE) at least possibly related to orteronel included grade 1-2 nausea (n = 4) and bone pain (n = 3), and grade 1 hypokalemia, hot flashes, myalgia and AST elevation (n = 2). The only grade 3 AE was hypertension (n = 2) with 8 patients receiving 34 cycles of treatment. No objective responses were seen; clinical benefit was seen in 2 patients with stable disease for more than 6 months. Serum estrogens and testosterone were suppressed from baseline on both doses of orteronel. Conclusions Orteronel 400 mg BID is well tolerated in postmenopausal women, and significantly suppresses serumestrogens and testosterone. Clinical benefit was seen among heavily pretreated postmenopausal women with HR+ metastatic breast cancer.
Details
- Title: Subtitle
- Phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR plus ) metastatic breast cancer
- Creators
- Murtuza Rampurwala - University of Wisconsin Carbone Cancer CenterKari B. Wisinski - University of Wisconsin Carbone Cancer CenterMark E. Burkard - University of Wisconsin Carbone Cancer CenterSima Ehsani - University of Wisconsin Carbone Cancer CenterRuth M. O'Regan - Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USALakeesha Carmichael - University of Wisconsin–MadisonKyungMann Kim - University of Wisconsin Carbone Cancer CenterJill Kolesar - University of Wisconsin Carbone Cancer CenterAmye J. Tevaarwerk - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Investigational new drugs, Vol.35(1), pp.87-94
- DOI
- 10.1007/s10637-016-0403-2
- PMID
- 27826831
- PMCID
- PMC5590750
- NLM abbreviation
- Invest New Drugs
- ISSN
- 0167-6997
- eISSN
- 1573-0646
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- UL1TR000427; KL2TR000428 / Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) Millennium Pharmaceuticals; Takeda Pharmaceutical Company Ltd U01CA062491 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) KL2RR025012 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) KL2TR000428 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) P30 CA014520; NCI U01CA062491 / NCI Cancer Center Support Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 02/01/2017
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984696538602771
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