Summary:Doxorubicin plus paclitaxel has been shown to be an active regimen for metastatic breast cancer and is now frequently used as adjuvant therapy for high-risk primary breast cancer. Initial studies reported a higher than expected rate of cardiac toxicity with this regimen. We studied 105 patients with either high-risk primary breast cancer or metastatic breast cancer who were treated with doxorubicin ( Keywords: autologous; transplantation; breast cancer; doxorubicin; cardiotoxicity A previous study of the combination of doxorubicin, 5-fluorouracil and methotrexate as an induction regimen prior to HDC and PBPCT showed significant activity with a CR rate of 23% and a PR rate of 46% for an overall response of 72% in women with metastatic breast cancer. 1 While the regimen showed very good activity it also had a significant toxicity profile with mucositis being a major drawback. As a consequence we were eager to define an alternative induction regimen for use in our next generation trials of HDC with hematopoietic cell support. Paclitaxel (Taxol; BristolMeyers Squibb, Princeton, NJ, USA) was the initial taxane evaluated in the treatment of metastatic breast cancer. It was found to be an active agent both in patients who were chemotherapy naive and in those who were anthracyclineresistant. 2,3 The significant activity of paclitaxel plus the established role of doxorubicin in breast cancer, led to the logical choice of the combination of these two agents as an induction regimen. [4][5][6][7] Gianni and coworkers 8 first reported the combination of doxorubicin and a 3-h infusion of paclitaxel in 1995. They established that a significant number of women (94%) with previously untreated metastatic breast cancer responded to this combination. Unfortunately, a higher number of patients in this and subsequent studies developed cardiac arrhythmia and congestive heart failure at doxorubicin doses lower than previously reported for doxorubicin alone. 9,10 Combinations of paclitaxel with other agents have indicated that the sequence and infusion rates of the respective agents have a significant effect on the maximum tolerated dose (MTD). When paclitaxel, doxorubicin and cyclophosphamide were given in a sequential fashion rather than concurrently no increase in cardiac toxicity was observed. 11 Studies employing longer infusions of both paclitaxel and doxorubicin found a sequence-dependent difference in the dose-limiting toxicity. 12 With a short infusion of doxorubicin and a 3-h infusion of paclitaxel the MTD did not appear to be affected by the drug sequence. 8 Pharmacokinetic companion studies of this combination demonstrated

No abstract