Taguchi T, Wakui A, Niitani H, Furue H, Majima H, Nakao I, Ota K, Hattori T, Sugimachi K
Research Institute for Microbial Diseases, Osaka University (Japan Society for Cancer Chemotherapy at present).
Gan To Kagaku Ryoho. 1997 Jul;24(9):1125-33.
A phase I study with TUT-7, a new anthracycline antitumor antibiotic, was conducted in 35 malignant tumor patients at 11 institutions nationwide. The study was initiated with a single dose at 100 mg/body which was equivalent to 2n, then the dose as escalated up to 700 mg/body in accordance with the modified Fibonacci's scheme. The dose limiting factor (DLF) was considered to be leukopenia, and maximum tolerated dose (MTD) was 700 mg/ body. The consecutive days dosing study subsequently conducted started with 25 mg/body/day, and the dose level was escalated up to 150 mg /body/day. TUT-7 was orally administered for seven (7) to fourteen (14) consecutive days in principle. It was considered that DLF was leukopenia and MTD was 100 mg/body/day for consecutive days dosing. The study indicated that serum drug concentrations reached their plateaus on the 5th day after initiation of TUT-7 treatment and the accumulation of this compound was low. With these findings, a regimen with a dose of 100 mg/body/day orally administered for 14 consecutive days was recommended for early phase II studies.
一项针对新型蒽环类抗肿瘤抗生素TUT-7的I期研究在全国11家机构的35名恶性肿瘤患者中开展。该研究起始剂量为100mg/体，相当于2n，之后按照改良斐波那契方案将剂量递增至700mg/体。剂量限制因素（DLF）被认为是白细胞减少，最大耐受剂量（MTD）为700mg/体。随后进行的连续给药研究起始剂量为25mg/体/天，剂量水平递增至150mg/体/天。TUT-7原则上连续7至14天口服给药。连续给药时，DLF被认为是白细胞减少，MTD为100mg/体/天。该研究表明，TUT-7治疗开始后第5天血清药物浓度达到平台期，且该化合物的蓄积量较低。基于这些发现，推荐在II期早期研究中采用100mg/体/天连续14天口服给药的方案。
