Hainsworth J D, Jones S E, Mennel R G, Blum J L, Greco F A
Sarah Cannon-Minnie Pearl Cancer Center Nashville, TN 37203, USA.
J Clin Oncol. 1996 May;14(5):1611-6. doi: 10.1200/JCO.1996.14.5.1611.
Paclitaxel is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. In this phase II study, we added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin (NFL).
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 (i.v.) infusion on day 1, mitoxantrone 10 mg/m2 by i.v. bolus on day 1, 5-FU 350 mg2/m by i.v. bolus on days 1, 2, and 3, and leucovorin 300 mg i.v. over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients.
Twenty-three of 45 assessable patients (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. Hospitalization for treatment of fever during neutropenia was required in 13% of courses, and two patients died as a result of sepsis. Two patients developed severe congestive heart failure after a large cumulative anthracycline dose.
This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than anticipated based on previous results with the NFL regimen or with paclitaxel administered at this dose and schedule as a single agent. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with the paclitaxel/doxorubicin combination.
紫杉醇是治疗乳腺癌的一种高效单药。然而，其在联合方案中的最佳应用仍有待确定。在这项II期研究中，我们将通过1小时静脉输注给药的紫杉醇添加到先前描述的包含米托蒽醌、氟尿嘧啶（5-FU）和大剂量亚叶酸钙（NFL）的联合方案中。
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-FU 350mg/m²，第1、2和3天在5-FU前30至60分钟静脉输注亚叶酸钙300mg。对于有反应的患者，每3周进行一个疗程，共进行8个疗程。
45例可评估患者中有23例（51%）有主要反应。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%的疗程导致3级或4级白细胞减少。13%的疗程需要因中性粒细胞减少期间发热住院治疗，2例患者因败血症死亡。2例患者在累积大剂量蒽环类药物后发生严重充血性心力衰竭。
该联合方案作为转移性乳腺癌的一线或二线治疗具有活性，尽管其与其他联合方案或单独使用紫杉醇相比的活性尚不清楚。骨髓抑制比基于先前NFL方案或按此剂量和给药方案单独使用紫杉醇的结果预期的更严重。这些患者中心脏毒性的罕见发生表明紫杉醇/米托蒽醌联合方案可能不存在先前报道的紫杉醇/阿霉素联合方案的问题。
