Sørensen B, Bastholt L, Mirza M R, Gjedde S B, Jakobsen P, Mouridsen H T, Rose C
Department of Oncology, Odense University Hospital, Denmark.
Cancer Chemother Pharmacol. 1994;34(5):439-43. doi: 10.1007/BF00685571.
The purpose of this study was to determine the maximal tolerable dose (MTD) of epirubicin and ADR-529 given in combination with cyclophosphamide, 5-fluorouracil, and tamoxifen. A total of 64 breast cancer patients with locally advanced disease or a first metastatic event were included. Using fixed doses of cyclophosphamide, 5-fluorouracil, and tamoxifen, cohorts of ten patients were treated with escalating doses of epirubicin and ADR-529. With the use of protocol criteria specifying evaluation after the first course, the MTD was not reached. Dose reductions carried out due to hematologic toxicity during the first four courses made it impossible to escalate doses of epirubicin beyond 80 mg/m2 given together with ADR-529 600 mg/m2. The vascular toxicity of ADR-529 necessitated central venous access in a number of patients. For phase III evaluation of ADR-529 given together with cyclophosphamide, epirubicin, 5-fluorouracil, and tamoxifen (CEF/TAM) we recommend using epirubicin/ADR-529 at 60/600 mg/m2. Together with evaluation of the cardioprotective properties of ADR-529, we recommend evaluating the impact of ADR-529 on the efficacy of cytotoxic therapy and investigating further the toxicity of ADR-529.
本研究的目的是确定表柔比星和ADR - 529与环磷酰胺、5-氟尿嘧啶和他莫昔芬联合使用时的最大耐受剂量（MTD）。共纳入64例局部晚期疾病或首次发生转移事件的乳腺癌患者。使用固定剂量的环磷酰胺、5-氟尿嘧啶和他莫昔芬，每组10例患者接受递增剂量的表柔比星和ADR - 529治疗。根据方案标准规定在第一个疗程后进行评估，未达到MTD。由于前四个疗程期间的血液学毒性而进行的剂量减少使得表柔比星与600 mg/m²的ADR - 529联合使用时的剂量无法超过80 mg/m²。ADR - 529的血管毒性使得一些患者需要进行中心静脉置管。对于ADR - 529与环磷酰胺、表柔比星、5-氟尿嘧啶和他莫昔芬（CEF/TAM）联合使用的III期评估，我们建议使用60/600 mg/m²的表柔比星/ADR - 529。在评估ADR - 529的心脏保护特性的同时，我们建议评估ADR - 529对细胞毒性治疗疗效的影响，并进一步研究ADR - 529的毒性。
