low dose estradiol for AI resistance
A revalidation of Dr. Matthew Ellis low dose estradiol work. This time with only 2mg.
Nguyen SABCS 2012: P2-14-06 A phase II trial of low dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to an aromatase inhibitor. Howell SJ, Seif MW, Armstrong AC, Cope J, Wilson G, Welch RS, Misra V, Ryder D, Blowers E, Palmieri C, Wardley AM. University of Manchester, United Kingdom; The Christie NHS Foundation Trust, Manchester, United Kingdom; Imperial College, London, United Kingdom Background High dose estrogen (HDE) is an effective but toxic treatment for postmenopausal women with advanced breast cancer (ABC). In vitro, prolonged periods of estrogen deprivation (ED) sensitises cancers to the inhibitory effects of estrogen. We hypothesised that the profound ED seen with third generation aromatase inhibitor (AI) would sensitise cancers to LDE which would be better tolerated. Methods Single arm phase II study in postmenopausal women with measurable ER+ ABC and demonstrated clinical benefit (CB) with a third generation AI. Treatment: estradiol valerate 2mg daily. Primary endpoint: CB rate (CBR) was correlated with baseline and dynamic LH/FSH levels and on-treatment estradiol levels. Secondary endpoints included TTF, PFS, toxicity and QoL. If LDE was effective, retreatment with the AI on which the cancer had progressed prior to study entry was offered on progression. If LDE was ineffective HDE was offered. Results 21/50 patients were recruited before early closure due to slow accrual. 19 were assessable for efficacy and toxicity (1 ineligible; 1 no LDE). CBR was 5/19 (26%; 95%CI 9.1%,51.2%). Median TTF 2.8months (range 0.5-29.8). CBR durations were 11.1, 16.8, 17.3*, 19.8, 29.8 months (*censored). 4 stopped treatment early due to toxicity (G4 hypercalcaemia/ G2 vaginal bleeding (VB) plus G4 hyponatraemia/ G2 mucositis/ G2 headaches) 1 with SD at 3 months and 3 before response assessment. Other common toxicities were all G1/2 and mainly limitted to nausea (8/19), breast pain (7/19) and tumour flare (7/19). VB occurred in 8/11 without prior hysterectomy. Baseline LH correlated with CBR by logistic regression (p=0.01). Of 3 retreated with the same AI post LDE; 1 had PR, 1 SD ≥6months and 1 PD. One woman received HDE after failure of LDE and achieved a PR. Conclusion LDE is an effective and largely well tolerated treatment in women with acquired resistance to AI. VB is common without prior hysterectomy. Rechallenge with the same AI post LDE seems effective and may offer an extra line of endocrine therapy. This should be tested in future trials. |
All times are GMT -7. The time now is 01:47 AM. |
Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2024, vBulletin Solutions, Inc.
Copyright HER2 Support Group 2007 - 2021