Greco F A, Hainsworth J D
Sarah Cannon-Minnie Pearl Cancer Center, Nashville, TN 37203, USA.
Semin Oncol. 1997 Oct;24(5 Suppl 17):S17-61-S17-64.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. We added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, 5-fluorouracil, and high-dose leucovorin. Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous infusion on day 1; mitoxantrone 10 mg/m2 by intravenous bolus on day 1; 5-fluorouracil 350 mg/m2 by intravenous bolus on days 1, 2, and 3; and leucovorin 300 mg intravenous over 30 to 60 minutes, immediately preceding 5-fluorouracil on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients. Of 45 assessable patients, 23 (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. There were four treatment-related deaths, two sepsis, one congestive heart failure, and one sepsis and congestive heart failure, the last two after a large cumulative anthracycline dose. This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although how its activity compares with that of other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than had been anticipated based on previous results with the mitoxantrone/5-fluorouracil/high-dose leucovorin regimen or with single-agent paclitaxel administered at this dose and schedule. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with paclitaxel/doxorubicin combinations. We have embarked on a phase I/II trial of paclitaxel/mitoxantrone and have determined the maximum tolerated dose to be 200 mg/m2 and 10 mg/m2, respectively, without the use of cytokines. Fifteen patients have been treated at the maximum tolerated dose, and it is too early to assess results.
紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）是治疗乳腺癌的一种高效单药。然而，其在联合治疗方案中的最佳应用仍有待确定。我们将通过1小时输注给药的紫杉醇添加到先前描述的包含米托蒽醌、5-氟尿嘧啶和大剂量亚叶酸钙的联合治疗方案中。46例转移性乳腺癌患者接受以下方案作为一线或二线治疗：第1天静脉输注1小时给予紫杉醇135mg/m²；第1天静脉推注米托蒽醌10mg/m²；第1、2和3天静脉推注5-氟尿嘧啶350mg/m²；第1、2和3天在5-氟尿嘧啶前30至60分钟静脉输注亚叶酸钙300mg。对有反应的患者每3周进行一个疗程，共8个疗程。45例可评估患者中，23例（51%）有显著反应。既往化疗，尤其是既往使用阿霉素治疗，不影响反应率。中位反应持续时间为7.5个月。骨髓抑制为中度严重，76%的疗程出现3或4级白细胞减少。有4例治疗相关死亡，2例败血症，1例充血性心力衰竭，1例败血症合并充血性心力衰竭，后两例发生在累积阿霉素剂量较大之后。这种联合治疗方案作为转移性乳腺癌的一线或二线治疗是有效的，尽管其活性与其他联合治疗方案或单独使用紫杉醇相比如何尚不清楚。骨髓抑制比基于先前米托蒽醌/5-氟尿嘧啶/大剂量亚叶酸钙方案或此剂量和给药方案的单药紫杉醇治疗结果预期的更严重。这些患者中不常见的心脏毒性表明紫杉醇/米托蒽醌联合可能不存在先前报道的紫杉醇/阿霉素联合的问题。我们已开展紫杉醇/米托蒽醌的I/II期试验，并确定在不使用细胞因子的情况下最大耐受剂量分别为200mg/m²和10mg/m²。15例患者已接受最大耐受剂量治疗，评估结果为时尚早。
