Kattan J, Durand M, Droz J P, Mahjoubi M, Marino J P, Azab M
Institut Gustave-Roussy, Villejuif, France.
Am J Clin Oncol. 1994 Jun;17(3):242-5. doi: 10.1097/00000421-199406000-00013.
Retelliptine dihydrochloride (SR 95325 B, NSC D-626717-W) is an ellipticine derivative having a very high level of antitumor activity in resistant murine solid tumor models. We studied in a Phase I trial escalating doses of retelliptine using a single 2-hour IV infusion schedule. Data from other Phase I studies allowed a starting dose of 80 mg/m2 and a rapid dose escalation. Included were 15 patients (M/F = 13/2) with a median age of 55 (range: 17-72). There were 22 courses delivered at the following dose levels: 80, 180, 700, 900, 1,200, and 1,500 mg/m2. Primary tumor types were kidney (6 patients), colon (3 patients), pancreas (2 patients), and others (4 patients). Mild dose-related visual troubles (blurring, accommodation troubles, oculomotor paresis) occurred in 9/11 patients starting from 700 mg/m2. Asymptomatic EKG anomalies, including significant prolongation of PR and QRS intervals occurred at 1500 mg/m2 (in 3/3 patients) marking the maximum tolerated dose. Both visual and EKG anomalies were spontaneously reversible few minutes to few hours after the end of infusion. Other possible drug-related toxicity occurred sporadically such as somnolence, bronchospasm, dry mouth, and vomiting (2 patients each). There were no significant laboratory anomalies. Neither drug-related deaths nor objective complete or partial responses were observed. The recommended dose for Phase II trial using the 2-hour intravenous infusion schedule is 1,200 mg/m2.
盐酸瑞替林（SR 95325 B，NSC D - 626717 - W）是一种椭圆玫瑰树碱衍生物，在耐药小鼠实体瘤模型中具有非常高的抗肿瘤活性。我们在一项I期试验中，采用单次2小时静脉输注方案递增瑞替林剂量进行研究。来自其他I期研究的数据使得起始剂量为80 mg/m²，并能快速递增剂量。入组的15例患者（男/女 = 13/2），中位年龄为55岁（范围：17 - 72岁）。在以下剂量水平进行了22个疗程给药：80、180、700、900、1200和1500 mg/m²。原发肿瘤类型为肾（6例患者）、结肠（3例患者）、胰腺（2例患者）和其他（4例患者）。从700 mg/m²起，9/11例患者出现轻度剂量相关视觉问题（视物模糊、调节障碍、动眼神经麻痹）。在1500 mg/m²时（3/3例患者）出现无症状心电图异常，包括PR和QRS间期显著延长，这标志着最大耐受剂量。视觉和心电图异常在输注结束后几分钟到几小时内可自发逆转。其他可能与药物相关的毒性反应偶尔出现，如嗜睡、支气管痉挛、口干和呕吐（各2例患者）。未出现显著的实验室异常。未观察到与药物相关的死亡，也未观察到客观的完全或部分缓解。采用2小时静脉输注方案进行II期试验的推荐剂量为1200 mg/m²。
