Lluch A, Ojeda B, Colomer R, Barnadas A, Massuti B, Casado A, Angeles C, Maroto P
Hospital Clínico, Valencia, Spain.
Cancer. 2000 Dec 1;89(11):2169-75. doi: 10.1002/1097-0142(20001201)89:11<2169::aid-cncr4>3.0.co;2-9.
The authors undertook a Phase II multicenter trial to assess the efficacy and toxicity of doxorubicin and paclitaxel in combination in the treatment of patients with metastatic breast carcinoma.
Doxorubicin (50 mg/m2, bolus) followed by paclitaxel (175 mg/m2 over 3 hours) was administered every 21 days (for a maximum of 10 cycles) as first-line chemotherapy in 77 patients, 41 of whom had received prior adjuvant chemotherapy. Monitoring of cardiac function (left ventricular ejection fraction[LVEF]) and total doxorubicin cumulative dose were included in the study protocol.
Grade 4 hematologic toxicities were neutropenia (58%) and thrombocytopenia (4%). Neutropenic fever occurred in 9% of patients. Nonhematologic Grade 4 toxicity was limited to mucositis (3%). Grade 3 toxicities were neutropenia (35%), anemia (3%), alopecia (93%), peripheral neuropathy (18%), arthralgia/myalgia (8%), and mucositis (9%). No clinical cardiotoxicity (Grades 3 or 4) occurred. Treatment was discontinued in 5 patients who showed a decrease of LVEF of greater than 15% during therapy. Of 73 patients assessable for response, 15 were complete response, 42 partial response, 15 stable disease, and 1 disease progression; overall response rate being 78% (95% confidence interval [CI], 67-87). Median follow-up was 22 months. Median time to progression (TP) was 10 months (95% CI, 7-12). Time to progression was poorer in cases with adjuvant anthracycline therapy than those without adjuvant chemotherapy (7 vs. 12.3 months; P = 0.022), but TP in patients with adjuvant chemotherapy not containing anthracyclines was not different from the cases without adjuvant chemotherapy (8.6 months). Estimated 2-year survival was 51% (standard error, 7%).
Our results confirm that the combination of paclitaxel and doxorubicin is effective in the treatment of metastatic breast carcinoma, and that it is well tolerated. No clinical cardiotoxicity was observed on close cardiac monitoring, and prior adjuvant anthracycline treatment compromised its efficacy.
作者进行了一项II期多中心试验，以评估阿霉素和紫杉醇联合治疗转移性乳腺癌患者的疗效和毒性。
77例患者接受阿霉素（50mg/m²，静脉推注），随后紫杉醇（175mg/m²，3小时输注），每21天给药一次（最多10个周期）作为一线化疗，其中41例患者曾接受过辅助化疗。研究方案包括监测心功能（左心室射血分数[LVEF]）和阿霉素的总累积剂量。
4级血液学毒性为中性粒细胞减少（58%）和血小板减少（4%）。9%的患者发生中性粒细胞减少性发热。非血液学4级毒性仅限于粘膜炎（3%）。3级毒性为中性粒细胞减少（35%）、贫血（3%）、脱发（93%）、周围神经病变（18%）、关节痛/肌痛（8%）和粘膜炎（9%）。未发生临床心脏毒性（3或4级）。5例患者在治疗期间LVEF下降超过15%，治疗中断。在73例可评估反应的患者中，15例完全缓解，42例部分缓解，15例病情稳定，1例疾病进展；总缓解率为78%（95%置信区间[CI]，67 - 87）。中位随访时间为22个月。中位疾病进展时间（TP）为10个月（95%CI，7 - 12）。接受过辅助蒽环类治疗的患者疾病进展时间比未接受辅助化疗的患者差（7对12.3个月；P = 0.022），但接受不含蒽环类药物辅助化疗的患者的TP与未接受辅助化疗的患者无差异（8.6个月）。估计2年生存率为51%（标准误，7%）。
我们的结果证实，紫杉醇和阿霉素联合治疗转移性乳腺癌有效，且耐受性良好。密切心脏监测未观察到临床心脏毒性，先前的辅助蒽环类治疗会损害其疗效。
