Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer:: A multicentric phase I-II study
Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer:: A multicentric phase I-II study
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DOI：
10.1023/a:1008392927656
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发表时间：
2000-08-01
影响因子：
50.5
通讯作者：
Goldhirsch, A
中科院分区：
文献类型：
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作者：
Pagani, O;Sessa, C;Goldhirsch, A
背景资料：蒽环类和紫杉烷类的组合目前被认为是晚期乳腺癌（ABC）的首选化疗，并且相当重视探索最安全和最有效的方式将这些类别的药物整合到转移性乳腺癌和最近的乳腺癌中的方案。我们在此报告了表阿霉素（E）90 mg/m2和多西他赛（D）75 mg/m2联合治疗的总体结果，作为第一次治疗。患者和方法：共有70名患者进入初始剂量探索研究（20名患者）和随后的扩展II期试验（50名患者）。总体而言，54%的患者有显性内脏疾病，57%的患者至少有两个转移部位。基于在I期研究中观察到的中位累积E剂量为480 mg/m2时没有心脏毒性，允许在研究的II期部分使用辅助蒽环类药物（2）。允许最多8个周期的组合，并在基线和每隔一个疗程后通过超声心动图监测心脏功能。结果：总体而言，与组合管理的周期数中位数为4（范围3-8）。中性粒细胞增多症被证实是主要的血液学毒性，44%的周期需要粒细胞集落刺激因子（G-CSF）支持。发热性中性粒细胞减少症发生在12%的联合治疗周期中，但52%的发作可以在门诊使用口服抗生素进行管理。总体而言，E的中位累积剂量（包括既往辅助蒽环类药物）为495 mg/m2（范围270-1020 mg/m2）。1例患者接受辅助E联合左胸壁放疗，在累积剂量为870 mg/m2的E后，出现完全可逆的心脏毒性临床体征，LVEF显著下降至35%（2），另外4例患者（6%）出现无症状和短暂的静息LVEF下降。68例可评价患者的总缓解率（ORR）为66%（95%置信区间（95%CI）：54%-73%）。在既往接受过蒽环类药物辅助化疗的患者组中报告了71%的可比抗肿瘤活性。总体中位随访时间为22个月（范围4-39+）后，中位至进展时间（TTP）为4.5个月，中位缓解持续时间为8个月（范围3-16）。没有药代动力学（PK）之间的相互作用，可以证明E和D同时和顺序给予一个小时的intervation.Conclusions：在多机构设置的E和D的组合是一个积极和安全的方案，预后不良的ABC患者。新的组合和时间表值得考虑，以进一步改善疾病反应和疾病的长期控制。
Background: The combination of anthracyclines and taxanes is currently considered the first choice chemotherapy in advanced breast cancer (ABC) and considerable emphasis has been placed on programs exploring the safest and most efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting.We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m(2) and docetaxel (D) 75 mg/m(2) as first-line chemotherapy in ABC.Patients and methods: A total of 70 patients were entered in the initial dose-finding study (20 patients) and in the subsequent extended phase II trial (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity observed in the phase I study at a median cumulative E dose of 480 mg/m(2). A maximum of eight cycles of the combination was allowed, and cardiac function was monitored at baseline and after every second course by echocardiography.Results: Overall, the median number of cycles administered with the combination was 4 (range 3-8). Neutropenia was confirmed to be the main haematological toxicity, with granulocyte colony-stimulating factor (G-CSF) support required in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatient basis with oral antibiotics. Overall, the median cumulative dose of E, including prior adjuvant anthracyclines, was 495 mg/m(2) (range 270-1020 mg/m(2)). One patient who received adjuvant E together with radiotherapy to the left chest wall developed fully reversible clinical signs of cardiotoxicity and a significant decrease of LVEF to 35% after a cumulative E dose of 870 mg/m(2), with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 evaluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A comparable antitumour activity of 71% was reported in the group of patients with a prior adjuvant chemotherapy with anthracyclines. After an overall median follow-up time of 22 months (range 4-39+), the median time to progression (TTP) was 4.5 months and the median duration of response was 8 months (range 3-16). No pharmacokinetic (Pk) interaction could be demonstrated between E and D when given simultaneously and sequentially with a one-hour interval.Conclusions: The combination of E and D in a multi-institutional setting is an active and safe regimen in poor- prognosis patients with ABC. New combinations and schedules are worth considering in an attempt to further improve disease response and long-term control of the disease.