New Agents for Taxol-Resistant Breast Adenocarcinoma
Abstract
Taxol has proven to be very active in breast cancer; however, evidence for resistance to Taxol has emerged. One approach to overcoming drug resistance involves drug copolymers. The paclitaxel copolymer, PGA-TXL, has shown both reduced toxicity and greater tumor localization in animal models. It has also demonstrated reduced toxicity and greater ease of administration compared to Taxol in the clinic, and has shown activity in patients with Taxol-refractory tumors. MDA-MB-361 human breast adenocarcinoma cells were implanted orthotopically in the mammary fat pad of female nude mice. When tumor volumes reached 20 mm3, one group was treated with pGA-TXL, 180 mg/kg i.p. Two other groups received a multiple-dose regimen of either S or 10 mg/kg Taxol, i.p. Control tumor volumes increased 5.89+1- 0.43-fold (mean +1- SEM) over the next 35 days. Treatment with PGA-TXL was highly efficacious: the increase in tumor volumes in this group was 2.96+1- 0.31-fold during the same time period (p = 0.0006). The two Taxol-treated groups failed to demonstrate significant responses: tumor volumes increased 6.06+1- 0.25-fold (p = 0.74) and 4.29+1- 0.61 -fold (p = 0.101) for the 5 and 10 mglkg groups, respectively. The key results from this study indicates that even single-dose PGA-TXL is active against MDA-MB-3 61, an orthotopically-implanted human Her-2/neu over-expressing breast tumor model that is highly resistant to a multiple-dose regimen of Taxol. Our pre-clinical studies suggest that among the patients who could be considered for trials with PGA-TXL are those with tumors over-expressing HER-2/neu and refractory to conventional taxanes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA420165
Entities
People
- Jim Klostergeard
Organizations
- University of Houston