Dombernowsky P, Boesgaard M, Andersen E, Jensen B V
Department of Oncology, Herlev University Hospital, University of Copenhagen, Denmark.
Semin Oncol. 1997 Oct;24(5 Suppl 17):S17-15-S17-8.
The combination of bolus doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a 3-hour infusion is highly active in patients with metastatic breast cancer, but it has considerable cardiotoxicity. In this ongoing study, the potential effect of increasing the interval between administration of a short infusion of doxorubicin followed by a 3-hour infusion of paclitaxel was evaluated. Included were patients with metastatic breast cancer, who received doxorubicin 50 mg/m2 followed by paclitaxel 200 mg/m2 at intervals of 30 minutes, 4 hours, and 24 hours every 3 weeks. As of February 1997, 34 patients have been enrolled, two patients are too early to evaluate, and 13 are continuing treatment. The preliminary response rate is 69% (95% confidence interval, 50% to 84%), ranging from 60% to 80% within the three schedules. The main toxicities consisted of grade 3/4 neutropenia in 65% of all courses, with febrile neutropenia in 2%. Stomatitis and paresthesia were rare. To date, eight of 32 patients have developed abnormal left ventricular ejection fraction values and one patient has developed congestive heart failure. Our preliminary conclusions are that bolus doxorubicin followed by a 3-hour infusion of paclitaxel is highly active against metastatic breast cancer. The potential for cardiotoxicity with the regimen is reduced considerably if the maximum recommended cumulative dose of doxorubicin is reduced to 360 mg/m2 with a maximum single dose of 50 mg/m2.
大剂量阿霉素与紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合进行3小时输注，对转移性乳腺癌患者具有很高的活性，但有相当大的心脏毒性。在这项正在进行的研究中，评估了增加短时间输注阿霉素后再进行3小时输注紫杉醇的给药间隔的潜在效果。纳入的是转移性乳腺癌患者，每3周接受一次阿霉素50mg/m²，随后是紫杉醇200mg/m²，给药间隔分别为30分钟、4小时和24小时。截至1997年2月，已招募34例患者，2例患者因时间过早无法评估，13例患者仍在继续治疗。初步缓解率为69%（95%置信区间，50%至84%），在三种给药方案中范围为60%至80%。主要毒性包括在所有疗程中有65%出现3/4级中性粒细胞减少，2%出现发热性中性粒细胞减少。口腔炎和感觉异常很少见。迄今为止，32例患者中有8例出现左心室射血分数值异常，1例患者出现充血性心力衰竭。我们的初步结论是，大剂量阿霉素后再进行3小时输注紫杉醇对转移性乳腺癌具有很高的活性。如果将阿霉素的最大推荐累积剂量降至360mg/m²，最大单剂量降至50mg/m²，该方案的心脏毒性可能性将大大降低。
