ISSN:
1573-7217
Keywords:
breast cancer
;
dark adaptation
;
fenretinide
;
lipids
;
tamoxifen
;
transforming growth factor‐β
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor‐beta (TGF‐β) levels and serum lipids was also examined. Patientsand Methods: Thirty‐one patients were treated with tamoxifen (20mg po daily), and fenretinide (400mg po daily with a 3‐day drug holiday each month). Plasma TGF‐β testing was performed using isoform specific sandwich ELISA. Results: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER‐negative patients, and three hormone therapy naive ER‐positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of −13.5 mg/dl; p=0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p=0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-β1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. Conclusions: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1006216409688
Permalink
