Ando M, Watanabe T, Sasaki Y, Ying D F, Omuro Y, Katsumata N, Narabayashi M, Tokue Y, Fujii H, Igarashi T, Wakita H, Ohtsu T, Itoh K, Adachi I, Taguchi T
Department of Medicine, National Cancer Center Hospital, Tokyo, Japan.
Br J Cancer. 1998 Jun;77(11):1937-43. doi: 10.1038/bjc.1998.321.
To determine the maximum-tolerated doses (MTDs), the dose-limiting toxicities (DLTs) and the recommended doses for further trials of docetaxel in combination with a 5-day continuous infusion of 5-fluorouracil (5-FU) in advanced or recurrent breast cancer patients who had been treated previously with at least one chemotherapeutic regimen, patients were treated with docetaxel as a 1-h infusion on day 1 followed by 5-FU as a continuous infusion on days 1 through 5 every 3-4 weeks. Three or six patients were assessed at the following escalating dose levels of docetaxel/5-FU per day: 40/150, 40/300, 50/300, 50/500 and 60/500 mg m(-2). Nineteen patients entered this trial, of whom 18 could be assessed for adverse event and therapeutic efficacy. The DLTs were neutropenia and diarrhoea. The MTDs were 60 mg m(-2) of docetaxel on day 1 and 500 mg m(-2) per day of 5-day continuous infusion of 5-FU. One of 18 patients achieved a complete response and eight achieved partial response (over all response rate: 50%). The recommended doses of docetaxel and 5-day continuous infusion of 5-FU for a phase II trial are 50 mg m(-2) and 500 mg m(-2) per day every 3 or 4 weeks.
为确定多西他赛与5-氟尿嘧啶(5-FU)连续5天静脉输注联合用药时的最大耐受剂量(MTD)、剂量限制性毒性(DLT)以及进一步试验的推荐剂量,对先前至少接受过一种化疗方案治疗的晚期或复发性乳腺癌患者进行了研究。患者在第1天接受1小时静脉输注多西他赛,随后在第1至5天每3 - 4周接受一次5-FU连续静脉输注。按照多西他赛/5-FU每日递增剂量水平:40/150、40/300、50/300、50/500和60/500 mg m(-2)评估3或6名患者。19名患者进入该试验,其中18名可评估不良事件和治疗效果。DLT为中性粒细胞减少和腹泻。MTD为第1天多西他赛60 mg m(-2)以及5-FU连续5天每日500 mg m(-2)静脉输注。18名患者中有1名达到完全缓解,8名达到部分缓解(总缓解率:50%)。II期试验多西他赛和5-FU连续5天静脉输注的推荐剂量为每3或4周50 mg m(-2)和500 mg m(-2)每日。