Breast cancer is the most common cancer in women, affecting nearly 180,000 women annually. Unfortunately metastatic disease remains incurable with therapy largely palliative. Response rates of >30% are routinely achieved in previously untreated patients with the anthracyclines, taxanes, cyclophosphamide, methotrexate, and 5-flourouracil; response rates decrease significantly in previously treated patients. Oral therapy offers several advantages for patients undergoing palliative treatment including fewer venipunctures, lack of a vascular access device and less time spent in clinic. The development of effective oral chemotherapy agents would represent a significant advance in the care of women with metastatic breast cancer. Camptothecins are unique class of chemotherapeutic agents which limit DNA synthesis by inhibiting topoisomerase I activy. The cytotoxicity of topoisomerase I inhibitors is S-phase specific suggesting that prolonged exposure may be more important in determining efficacy than brief exposure to high drug concentrations. 9-Nitro camptotecin (RFS 2000,9-NC) is an orally available analogue of camptothecin with execellent bioavailability and acceptable toxicity in early clinical trials. This phase II trail will study the safety and efficacy of RFS 2000 in patients with refractory metastatic breast cancer. Ancillary laboratory studies will define the pharmacokinetics of RFS 2000 in this patients population and attempt to correlate levels of topoisomerase expression with toxicity. Eligible patients will receive RFS 2000 daily for five days followed by a two day rest period. Samples for pharmacokinetics and topoisomerase expression will obtained on day one of weeks one and five. Efficacy will be assessed after eight weeks of therapy.
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