Phase I study of combination therapy with weekly paclitaxel and cyclophosphatamide for advanced or recurrent breast cancer
© BioMed Central Ltd. 2009
Published: 23 June 2009
Although anthracycline is a key agent in breast cancer treatment, there is a concern that it may cause cardiotoxicity. Recently, the usefulness of combined therapy with docetaxel and cyclophos-phamide (C) was reported. Because paclitaxel (P) has different features, such as induction of apoptosis and anti-angiogenic activity on weekly administration, establishment of combination therapy of P/C is required. We initiated a phase I study to determine the maximum tolerated dose and the recommended dose (RD) of the combination therapy of P/C for advanced or recurrent breast cancer.
P was given intravenously on days 1, 8 and 15 and C on day 1, every 3 weeks. P was given at 80 mg/m2 for level 1 and 100 mg/m2 for level 2, and C at 600 mg/m2 for both. Onset of dose-limiting toxicity was evaluated during course 1, and tolerability through course 4.
Four patients each were enrolled in levels 1 and 2 from October 2006 to November 2007. Main adverse events were four cases of grade 3 neutropenia (50%) and one case of peripheral nerve disorder (12.5%). During the first course of levels 1 and 2, hematologic toxicity of grade 4 and nonhematologic toxicity of grade 3 or higher were not observed, and a MTD was not attained. The response rate among assessable cases (one in level 1, two in level 2) was 66.7%.
Safety was confirmed during four courses at level 2, and this was regarded as the RD. This is the first report on the phase I study of the combination therapy of weekly P and C, and its safety and efficacy should be evaluated in the phase II trial.