Fracasso Paula M, Rodriguez Luis C, Herzog Thomas J, Fears Carole L, Goodner Sherry A, Govindan Ramaswamy, Picus Joel, Rader Janet S, Tan Benjamin R, Arquette Matthew A
Alvin J. Siteman Cancer Center, St. Louis, Missouri 63110, USA.
Cancer. 2003 Aug 1;98(3):610-7. doi: 10.1002/cncr.11547.
Pegylated liposomal doxorubicin (PEG-LD) and docetaxel have single-agent activity in several malignancies. The authors conducted a Phase I trial to evaluate the maximum tolerated dose (MTD), toxicities, and effect of dose sequencing of this combination in patients with advanced malignancies.
Twenty-two patients were enrolled in this two-arm, accelerated, dose escalation trial. Both drugs were administered on Days 1 and 15 of a 28 day cycle. In Arm A, dose escalation proceeded from a sequence and starting dose of 15 mg/m(2) PEG-LD and 30 mg/m(2) docetaxel. In Arm B, dose escalation proceeded from a sequence and starting dose of 30 mg/m(2) docetaxel and 15 mg/m(2)PEG-LD. In both arms, the dose of each drug was increased alternately by 5 mg/m(2) at each dose level.
The MTD for Arm A was 20 mg/m(2) PEG-LD and 40 mg/m(2) docetaxel, both of which were administered on Days 1 and 15 of a 28-day cycle. The MTD for Arm B was 35 mg/m(2) docetaxel and 20 mg/m(2) PEG-LD, both of which were administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicities were Grade 3 (according to the National Cancer Institute Common Toxicity Criteria) skin toxicity and thrombocytopenia. One partial response was observed and stable disease was documented for three patients.
The recommended sequence and dose is 20 mg/m(2) PEG-LD followed by 40 mg/m(2) docetaxel on Days 1 and 15 of a 28-day cycle in Phase II trials for patients with breast and ovarian carcinoma to establish the efficacy of this well tolerated regimen.
聚乙二醇化脂质体阿霉素（PEG-LD）和多西他赛在多种恶性肿瘤中具有单药活性。作者开展了一项I期试验，以评估该联合用药在晚期恶性肿瘤患者中的最大耐受剂量（MTD）、毒性及剂量给药顺序的影响。
22例患者入组了这项双臂、加速剂量递增试验。两种药物均在28天周期的第1天和第15天给药。A组剂量递增从15mg/m²PEG-LD和30mg/m²多西他赛的给药顺序及起始剂量开始。B组剂量递增从30mg/m²多西他赛和15mg/m²PEG-LD的给药顺序及起始剂量开始。在两组中，每种药物的剂量在每个剂量水平交替增加5mg/m²。
A组的MTD为20mg/m²PEG-LD和40mg/m²多西他赛，二者均在28天周期的第1天和第15天给药。B组的MTD为35mg/m²多西他赛和20mg/m²PEG-LD，二者均在28天周期的第1天和第15天给药。剂量限制性毒性为3级（根据美国国立癌症研究所通用毒性标准）皮肤毒性和血小板减少症。观察到1例部分缓解，3例患者病情稳定。
在针对乳腺癌和卵巢癌患者的II期试验中，推荐的给药顺序和剂量为在28天周期的第1天和第15天，先给予20mg/m²PEG-LD，随后给予40mg/m²多西他赛，以确定这种耐受性良好的方案的疗效。
