Taguchi T, Furuse K, Fukuoka M, Shimoyama T, Morimoto K, Nakamura T, Furue H, Majima H, Niitani H, Ohta K, Wakui A, Nakao I, Tsukagoshi S
Dept. of Surgery, Osaka University (currently: Japan Society for Cancer Chemotherapy).
Gan To Kagaku Ryoho. 1996 Jul;23(8):1011-8.
LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
LY188011（盐酸吉西他滨）是脱氧胞苷的一种新衍生物。一项I期研究由一个合作研究小组开展。LY188011每周给药，连续给药3周，初始剂量为60mg/m²（1倍剂量），随后将剂量增加至1000mg/m²（16.7倍剂量）。发现剂量限制因素为骨髓抑制（白细胞、中性粒细胞和血小板减少），最大耐受剂量被认为是1000mg/m²。白细胞和血小板的最低点在大约1 - 3周后出现。它们的恢复需要1 - 2周。其他不良反应包括发热、疲劳、厌食、恶心/呕吐、贫血以及谷草转氨酶和谷丙转氨酶的短暂升高。然而，这些不良反应较为轻微。血浆浓度的消除半衰期约为19分钟，5分钟时的血药浓度取决于剂量。在1例胃癌患者和2例结肠癌患者中观察到了抗癌效果。建议II期早期研究的给药方案为800mg/m²，每周给药1次，连续给药3周，休息1周为1个周期，进行多个周期。
