Misset J L, Dieras V, Gruia G, Bourgeois H, Cvitkovic E, Kalla S, Bozec L, Beuzeboc P, Jasmin C, Aussel J P, Riva A, Azli N, Pouillart P
Hôpital Paul Brousse, Villejuif, France.
Ann Oncol. 1999 May;10(5):553-60. doi: 10.1023/a:1026418831238.
To determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose of docetaxel in combination with doxorubicin, and to evaluate the activity in patients with advanced breast cancer.
Forty-two women with untreated metastatic breast cancer (79% with visceral metastases; 52% with prior adjuvant anthracycline therapy) were treated with doxorubicin (40-60 mg/m2) i.v. bolus followed one hour later by docetaxel (50-85 mg/m2) one-hour i.v. infusion every three weeks, without G-CSF support.
The MTD occurred at the dose level combining 85 mg/m2 of docetaxel and 50 mg/m2 of doxorubicin, with the DLT being neutropenic sepsis. Neutropenia and/or its complications were manageable and no grade 3-4 or severe non-hematological toxicities were observed. Fluid retention was frequent but never severe. With a median cumulative dose of doxorubicin of 392 mg/m2 (240-559 mg/m2) and a median follow-up time of 29 months (9(+)-41), no congestive heart failure was observed. High activity was observed at all dose levels, particularly the last four, with a response rate of 81% (95% confidence interval (95% CI): 62.5-92.5). Median time to progression was 46 weeks (6(+)-62). Two-year survival was 66%, and median survival has not yet been reached.
Docetaxel-doxorubicin is feasible, safe and highly active. The incidence of febrile neutropenia without G-CSF requires careful monitoring but is acceptable in this setting. There does not appear to be an increase in the cardiac toxicity of doxorubicin. The recommended doses is either docetaxel 75 mg/m2 and doxorubicin 50 mg/m2 or docetaxel 60 mg/m2 and doxorubicin 60 mg/m2, administered every three weeks.
确定多西他赛联合阿霉素的最大耐受剂量（MTD）、剂量限制性毒性（DLT）及推荐剂量，并评估其对晚期乳腺癌患者的疗效。
42例未经治疗的转移性乳腺癌女性患者（79%有内脏转移；52%曾接受蒽环类药物辅助治疗）接受阿霉素（40 - 60 mg/m²）静脉推注，1小时后给予多西他赛（50 - 85 mg/m²）静脉滴注1小时，每3周1次，不给予粒细胞集落刺激因子（G-CSF）支持。
MTD出现在多西他赛85 mg/m²与阿霉素50 mg/m²联合的剂量水平，DLT为中性粒细胞减少性败血症。中性粒细胞减少和/或其并发症可控，未观察到3 - 4级或严重的非血液学毒性。液体潴留常见但从不严重。阿霉素的中位累积剂量为392 mg/m²（240 - 559 mg/m²），中位随访时间为29个月（9（+）- 41），未观察到充血性心力衰竭。在所有剂量水平均观察到高活性，尤其是最后4个剂量水平，有效率为81%（95%置信区间（95%CI）：62.5 - 92.5）。中位疾病进展时间为46周（6（+）- 62）。2年生存率为66%，中位生存期尚未达到。
多西他赛 - 阿霉素联合方案可行、安全且活性高。在未使用G-CSF的情况下，发热性中性粒细胞减少的发生率需要密切监测，但在此情况下是可接受的。阿霉素的心脏毒性似乎未增加。推荐剂量为多西他赛75 mg/m²和阿霉素50 mg/m²，或多西他赛60 mg/m²和阿霉素60 mg/m²，每3周给药1次。
