Osaki Akihiko, Mitsuyama Shoshu, Kurebayashi Jun-Ichi, Sonoo Hiroshi, Nishimura Reiki, Koga Toshihiro, Murakami Shigeru, Ohno Shinji
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima-shi, Hiroshima 734-8551.
Oncol Lett. 2010 Jan;1(1):45-49. doi: 10.3892/ol_00000008. Epub 2010 Jan 1.
The study present the results of the dose-setting study of concomitant weekly administration of paclitaxel and tegafur·uracil (UFT) for metastatic breast cancer. Eligible patients who entered the study underwent two or more courses of weekly paclitaxel + UFT therapy as the protocol therapy. The initial dose (level 1) was paclitaxel, 80 mg/m(2) and UFT, 400 mg/day. At level 2, paclitaxel remained the same, but UFT was increased to 600 mg/day. At level 3, only paclitaxel was increased to 90 mg/m(2). Twelve patients were enrolled in this study between September 2000 and September 2002. Three patients were assigned to level 1. Grade 3 liver dysfunction (increased aspartate aminotransferase and alanine aminotransferase) was noted in one patient and grade 4 neutropenia was noted in one patient, showing that dose-limiting toxicity was detected in 2/3 patients. In accordance with the protocol, UFT was fixed at 400 mg/day and paclitaxel was decreased to 60 mg/m(2) at level -1, and then increased to 70 mg/m(2) at level 0. The overall effective rate after completion of two courses was 33% (3/9) including one case of complete response and two cases of partial responses. The remaining patients presented with stable diseases and no patient had progressive disease. In this study, weekly paclitaxel with concomitant UFT was administered. The recommended doses of paclitaxel and UFT were determined to be 70 mg/m(2) and 400 mg/day, respectively. As the toxicity profile shows, the highest toxicity level of this regimen was neutropenia and liver dysfunction, and dose-limiting toxicity was neutropenia.
本研究展示了转移性乳腺癌患者每周同步给予紫杉醇和替加氟尿嘧啶（UFT）剂量设定研究的结果。符合条件进入本研究的患者接受了两个或更多疗程的每周紫杉醇+UFT治疗作为方案治疗。初始剂量（1级）为紫杉醇80mg/m²和UFT 400mg/天。2级时，紫杉醇剂量不变，但UFT增加至600mg/天。3级时，仅将紫杉醇增加至90mg/m²。2000年9月至2002年9月期间，12例患者纳入本研究。3例患者被分配至1级。1例患者出现3级肝功能障碍（天冬氨酸转氨酶和丙氨酸转氨酶升高），1例患者出现4级中性粒细胞减少，表明2/3的患者检测到剂量限制性毒性。按照方案，UFT固定为400mg/天，紫杉醇在-1级降至60mg/m²，然后在0级增加至70mg/m²。两个疗程完成后的总有效率为33%（3/9），包括1例完全缓解和2例部分缓解。其余患者病情稳定，无患者病情进展。在本研究中，每周给予紫杉醇并同步给予UFT。确定紫杉醇和UFT的推荐剂量分别为70mg/m²和400mg/天。从毒性特征来看，该方案的最高毒性水平为中性粒细胞减少和肝功能障碍，剂量限制性毒性为中性粒细胞减少。
