The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers--a study of the National Cancer Institute of Canada Clinical Trials Group.
A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.
Duke Scholars
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Related Subject Headings
- Tumor Suppressor Proteins
- Tumor Suppressor Protein p53
- Triazoles
- Proto-Oncogene Proteins c-akt
- Proto-Oncogene Proteins
- Protein Serine-Threonine Kinases
- Postmenopause
- Phosphoric Monoester Hydrolases
- PTEN Phosphohydrolase
- Oncology & Carcinogenesis
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Proteins
- Tumor Suppressor Protein p53
- Triazoles
- Proto-Oncogene Proteins c-akt
- Proto-Oncogene Proteins
- Protein Serine-Threonine Kinases
- Postmenopause
- Phosphoric Monoester Hydrolases
- PTEN Phosphohydrolase
- Oncology & Carcinogenesis