Phase I study of combination therapy with weekly paclitaxel and cyclophosphamide for advanced or recurrent breast cancer

Abstract

Although anthracycline is a key agent in breast cancer treatment, its use is associated with the risk of cardiotoxicity. Recently, the value of combination therapy with docetaxel and cyclophosphamide was reported. Because the characteristics of paclitaxel differ on weekly versus tri-weekly administration, such as in the induction of apoptosis and anti-angiogenic activity, establishment of a treatment regimen with a combination of paclitaxel and cyclophosphamide (PC) is warranted. We initiated a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of combination therapy with PC for advanced or recurrent breast cancer. Eligible patients had advanced or recurrent breast cancer. Paclitaxel was given intravenously on days 1, 8, and 15 of every 3-week course, and cyclophosphamide on day 1, over a total of four courses. Paclitaxel was given at 80 mg/m(2) for level 1 and 100 mg/m(2) for level 2, and cyclophosphamide at 600 mg/m(2) in both cases. Onset of dose-limiting toxicity was evaluated during the first course, and tolerability throughout the four courses. Four patients were enrolled in each of levels 1 and 2 from October 2006 to November 2007. The main toxicities were grade 3 neutropenia in four patients (50%) and sensory neuropathy in one (12.5%). An MTD was not attained, as neither a hematologic toxicity of grade 4 nor a non-hematologic toxicity of grade 3 or higher was observed during the first course at level 1 or 2. Response rate amongst assessable patients (one in level 1, two in level 2) was 66.7%. Safety was well tolerated throughout the four courses at level 2, and this dosage level was therefore regarded as the RD.