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Abstract
Background
Our preclinical data have demonstrated that intraductal administration of PLD decreases
tumor volume, prevents the development of new lesions, and eradicates pre-malignant
disease. We initiated a phase I study to determine the feasibility, safety, and maximum
tolerated dose of PLD administered to women awaiting mastectomy.
Methods
Women 18 or older with a known breast cancer awaiting a mastectomy were eligible.
Neoadjuvant chemotherapy was allowed. Women with T4 features, prior breast irradiation,
or procedures that in the opinion of the investigator may have altered the breast
ductal system were excluded. Participants underwent nipple aspiration and ductal cannulation
using a dose escalation schema. The first 3 women received 5 mL intraductal dextrose
only. We determined serial doxorubicin and doxorubicinol concentrations in plasma
and nipple aspirate fluid using LC/MS/MS. We injected blue dye into the treated duct
just prior to mastectomy and obtained tissue for pharmacokinetic and biomarker analysis.
Results
From 02/06 to 09/08, 14 women entered the study, and 12 underwent study procedures
successfully. We completed all dose levels up to 10 mg PLD per one duct without serious
adverse events or surgical delays. Pharmacokinetic and representative histopathological
data will be presented.
Conclusion
Intraductal administration of PLD is feasible and can be safely administered both
in women with and without prior chemotherapy awaiting mastectomy. Studies to evaluate
other agents administered to one or more ducts are required.