New Agents for Taxol-Resistant Breast Adenocarcinoma
Annual rept. 1 Jul 2001-30 Jun 2002
M D ANDERSON CANCER CENTER HOUSTON TX
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Over-expression of HER-2neu has been linked to poorer prognosis and reduced survival in breast cancer patients. The basis for this association is likely multifactorial and includes therapeutic resistance, such as resistance to Taxol paclitaxel, widely used in many chemotherapeutic regimens for this disease. We have recently reported that a paclitaxel copolymer, polyL-glutamic acid-paclitaxel PGA-TXL, is active against Taxol-resistant human ovarian xenograft models in vivo Auzenne et al. Superior therapeutic profile of poly-L-glutamic acid-paclitaxel copolymer compared to Taxol in xenogeneic compartmental models of human ovarian carcinoma. Clin Cancer Res 8 573-581, 2002. We therefore evaluated PGA-TXL in human HER-2neu over-expressing MDA- 361 and lownull-expressing MDA-231 breast adenocarcinoma orthotopic xenograft models. PGA-TXL 20-37 paclitaxel, wIw was administered as a single dose of 180 mg paclitaxel equivalentskg i.p., near its MTD. Drug was administered either one week after tumor implantation or once tumors were 4-5 mm in diameter. Either regimen resulted in growth inhibition of 361 tumors, and even some apparent cures with early treatment p 0.04. An on-going experiment with the 231 model demonstrates a similar initial pattern. We conclude that systemic treatment with PGA-TXL is active against human breast adenocarcinoma orthotopic xenograft models despite overexpression of HER-2neu.
- Medicine and Medical Research