Lower-Dose vs High-Dose Oral Estradiol Therapy of Hormone Receptor–Positive, Aromatase Inhibitor–Resistant Advanced Breast Cancer
| Autor: | Aruna Kommareddy, Farrokh Dehdashti, Donna B. Jeffe, Feng Gao, Gini F. Fleming, Robert J. Crowder, Shohreh Jamalabadi-Majidi, Maura N. Dickler, Paula Silverman, P. Kelly Marcom, Barry A. Siegel, Matthew J. Ellis, Lisa A. Carey |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
medicine.medical_specialty Antineoplastic Agents Hormonal medicine.drug_class Breast Neoplasms Gastroenterology Article Breast cancer Fluorodeoxyglucose F18 Predictive Value of Tests Internal medicine medicine Humans Insulin-Like Growth Factor I Aromatase Adverse effect Aged Aged 80 and over Gynecology Aromatase inhibitor Estradiol biology Aromatase Inhibitors business.industry Cancer Estrogens General Medicine Middle Aged medicine.disease Survival Analysis Postmenopause Receptors Estrogen Drug Resistance Neoplasm Estrogen Positron-Emission Tomography Predictive value of tests Quality of Life biology.protein Female Breast disease Radiopharmaceuticals business Biomarkers |
| Zdroj: | JAMA. 302:774 |
| ISSN: | 0098-7484 |
| DOI: | 10.1001/jama.2009.1204 |
| Popis: | Estrogen deprivation therapy with aromatase inhibitors has been hypothesized to paradoxically sensitize hormone-receptor-positive breast cancer tumor cells to low-dose estradiol therapy.To determine whether 6 mg of estradiol (daily) is a viable therapy for postmenopausal women with advanced aromatase inhibitor-resistant hormone receptor-positive breast cancer.A phase 2 randomized trial of 6 mg vs 30 mg of oral estradiol used daily (April 2004-February 2008 [enrollment closed]). Eligible patients (66 randomized) had metastatic breast cancer treated with an aromatase inhibitor with progression-free survival (or = 24 wk) or relapse (afteror = 2 y) of adjuvant aromatase inhibitor use. Patients at high risk of estradiol-related adverse events were excluded. Patients were examined after 1 and 2 weeks for clinical and laboratory toxicities and flare reactions and thereafter every 4 weeks. Tumor radiological assessment occurred every 12 weeks. At least 1 measurable lesion or 4 measurable lesions (bone-only disease) were evaluated for tumor response.Randomization to receive 1 oral 2-mg generic estradiol tablet 3 times daily or five 2-mg tablets 3 times daily.Primary end point: clinical benefit rate (response plus stable disease at 24 weeks).toxicity, progression-free survival, time to treatment failure, quality of life, and the predictive properties of the metabolic flare reaction detected by positron emission tomography/computed tomography with fluorodeoxyglucose F 18.The adverse event rate (or = grade 3) in the 30-mg group (11/32 [34%]; 95% confidence interval [CI], 23%-47%) was higher than in the 6-mg group (4/34 [18%]; 95% CI, 5%-22%; P = .03). Clinical benefit rates were 9 of 32 (28%; 95% CI, 18%-41%) in the 30-mg group and 10 of 34 (29%; 95% CI, 19%-42%) in the 6-mg group. An estradiol-stimulated increase in fluorodeoxyglucose F 18 uptake (or = 12% prospectively defined) was predictive of response (positive predictive value, 80%; 95% CI, 61%-92%). Seven patients with estradiol-sensitive disease were re-treated with aromatase inhibitors at estradiol progression, among which 2 had partial response and 1 had stable disease, suggesting resensitization to estrogen deprivation.In women with advanced breast cancer and acquired resistance to aromatase inhibitors, a daily dose of 6 mg of estradiol provided a similar clinical benefit rate as 30 mg, with fewer serious adverse events. The efficacy of treatment with the lower dose should be further examined in phase 3 clinical trials.clinicaltrials.gov Identifier: NCT00324259. |
| Databáze: | OpenAIRE |
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