Lack of Increased Cardiac Toxicity with Sequential Doxorubicin and Paclitaxel

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Abstract
Introduction Recently, paclitaxel has joined doxorubicin as one of the most active single agents for the treatment of metastatic breast cancer (1,2). Because these drugs now appear to be non-cross-resistant, combinations have been studied using various doses and schedules to assess efficacy and toxicity (3-7). However, concurrent administration of the two drugs at full doses has been associated with increased toxicity. In particular, an increased incidence of congestive heart failure has been seen in two studies of doxorubicin plus concurrent paclitaxel (6,7). At our institution, we have been developing “dose-dense” chemotherapy applying doxorubicin, paclitaxel, and cyclophosphamide as adjuvant treatment for high-risk primary breast cancer. To minimize toxicity and maximize delivered dose intensity, these drugs are given sequentially in the above order rather than concurrently. Because of the suggestion that the use of doxorubicin and paclitaxel might increase the risk of cardiac toxicity, we reviewed our prospective nonrandomized phase II study of sequential doxorubicin and paclitaxel to determine the incidence of cardiotoxicity.