Sampi K, Masaoka T, Shibata H, Shirakawa S, Kobayashi T, Shirai T, Umeda M, Kozuru M, Sugiyama H, Oguro M
Gan To Kagaku Ryoho. 1986 Aug;13(8):2594-9.
A new doxorubicin analogue, epirubicin (EPI), has been evaluated in 11 institutions throughout Japan in a phase II study in patients with acute leukemia. A total of 41 patients were entered into this study between January 1983 and July 1985, and 34 were considered evaluable. Two patients were added for evaluation of toxicity. There were 25 males and 9 females with a median age of 43 years. Of the 34 evaluable patients, 24 had previously been treated with intensive combination chemotherapy, 21 with anthracyclines. The remaining ten were previously untreated patients. Underlying diseases were acute lymphocytic leukemia (ALL) in 15, acute non-lymphocytic leukemia (ANLL) in 17 and blastic crisis of chronic myelogenous leukemia (CML/BC) in 2. EPI was administered intravenously in two schedules, a high-dose regimen consisting of 24 to 60 mg/m2/day for 3 to 5 days and a low-dose regimen involving 11-17 mg/m2/day for 5 to 8 days. Responses were obtained in 5 (33.3%) of 15 patients with ALL, 3 of these attaining complete remission, 2 (11.8%) of 17 patients with ANLL and one (50.0%) of 2 patients with CML/BC. Out of the 21 patients who had received previous anthracyclines, 4 (19.1%) attained responses. Also, responses were obtained in 23.5% with the higher doses as well as 24% with the lower doses. The remission duration of responders was 1, 1, 3, 3, 3, 16+, 17 and 26 weeks, respectively. The major non-hematologic toxicity was stomatitis which occurred in 15 patients, in 11 of whom the symptoms were severe (Grade 3 or 4). This stomatitis was thought to be the dose limiting factor. On the basis of the above observations, we concluded that EPI was active against acute leukemia, especially ALL. Stomatitis was considered to be the dose-limiting factor, especially in the high-dose regimen. Toxicity was tolerable in the low-dose regimen.
一种新的阿霉素类似物表柔比星（EPI），在日本全国11家机构进行了针对急性白血病患者的II期研究评估。1983年1月至1985年7月期间共有41例患者进入本研究，其中34例被视为可评估对象。另外增加了2例患者以评估毒性。有25名男性和9名女性，中位年龄为43岁。在34例可评估患者中，24例此前接受过强化联合化疗，21例接受过蒽环类药物治疗。其余10例为初治患者。基础疾病为急性淋巴细胞白血病（ALL）15例，急性非淋巴细胞白血病（ANLL）17例，慢性粒细胞白血病急变期（CML/BC）2例。EPI采用两种给药方案静脉注射，一种高剂量方案为24至60mg/m²/天，持续3至5天，另一种低剂量方案为11 - 17mg/m²/天，持续5至8天。15例ALL患者中有5例（33.3%）获得缓解，其中3例达到完全缓解；17例ANLL患者中有2例（11.8%）缓解；2例CML/BC患者中有1例（50.0%）缓解。在21例此前接受过蒽环类药物治疗的患者中，4例（19.1%）获得缓解。此外，高剂量组缓解率为23.5%，低剂量组为24%。缓解者的缓解持续时间分别为1、1、3、3、3、16 +、17和26周。主要的非血液学毒性是口腔炎，15例患者出现口腔炎，其中11例症状严重（3级或4级）。这种口腔炎被认为是剂量限制因素。基于上述观察结果，我们得出结论，EPI对急性白血病，尤其是ALL有效。口腔炎被认为是剂量限制因素，特别是在高剂量方案中。低剂量方案中的毒性是可耐受的。
