Patzer D C, Koschel G, Greifenberg B, Kaukel E
Department of Pneumology, Harburg General Hospital, Hamburg, F.R.G.
Am J Clin Oncol. 1990;13 Suppl 1:S24-8. doi: 10.1097/00000421-199012001-00007.
The toxicity and efficacy of the combination of pirarubicin (THP), etoposide, and vincristine were investigated in a phase I trial. The dose of THP was modified in steps of 10 mg/m2 or 5 mg/m2 differences, starting with 40 mg/m2 i.v. on day 1. Doses of etoposide (100 mg/m2 i.v. days 1-3) and vincristin 2 mg i.v. day 1) remained constant. The schedule was repeated every 3 weeks. A minimum of four patients were recruited at each dose level. The maximum tolerated dose (MTD) was defined as follows: toxicity WHO grade 3 and 4 in five of eight patients of one dose step (exception: leukocytopenia at the time of nadir WHO grade 4 is relevant for the MTD). Currently, 20 patients have been treated. The administered dose levels of THP were (mg/m2); 40 (5 patients), 50 (4 patients), 55 (6 patients), and 60 (5 patients). Screening of cardiac function (ECG, ultrasound cardiography) was performed at the start of the treatment and before each course. There were no signs of cardiotoxicity up to a cumulative dose of 360 mg/m2. Leukocytopenia WHO grade 3 was observed in seven courses (12%), and grade 4 was observed in two courses (3%) as main side effects. The subjective tolerability (nausea, vomiting, and alopecia) was mild to moderate. We decided upon 55 mg/m2 MTD because WHO grade 4 leukocytopenia developed in one patient after the first course and two not conclusively clarified early deaths occurred at the 60 mg/m2 pirarubicin dose level. Eighteen patients were evaluable for response: one CR (6%), eight PR (44%), four NC (22%), one EP (6%), and four ED (22%). This means a response rate of 50% and a median survival time of 10 months. We have initiated a phase II study with the elaborated schedule.
在一项I期试验中研究了吡柔比星（THP）、依托泊苷和长春新碱联合应用的毒性和疗效。THP的剂量以10mg/m²或5mg/m²的差值逐步调整，起始剂量为第1天静脉注射40mg/m²。依托泊苷的剂量（第1 - 3天静脉注射100mg/m²）和长春新碱（第1天静脉注射2mg）保持不变。该方案每3周重复一次。每个剂量水平至少招募4名患者。最大耐受剂量（MTD）定义如下：一个剂量组的8名患者中有5名出现WHO 3级和4级毒性（例外情况：最低点时WHO 4级白细胞减少与MTD相关）。目前，已治疗20名患者。THP的给药剂量水平为（mg/m²）：40（5例患者）、50（4例患者）、55（6例患者）和60（5例患者）。在治疗开始时和每个疗程前进行心脏功能检查（心电图、超声心动图）。累积剂量达360mg/m²时未出现心脏毒性迹象。主要副作用方面，观察到7个疗程（12%）出现WHO 3级白细胞减少，2个疗程（3%）出现WHO 4级白细胞减少。主观耐受性（恶心、呕吐和脱发）为轻度至中度。我们确定MTD为55mg/m²，因为1例患者在第一个疗程后出现WHO 4级白细胞减少，并且在吡柔比星剂量为60mg/m²时发生了2例原因未明确的早期死亡。18名患者可评估疗效：1例完全缓解（CR，6%）、8例部分缓解（PR，44%）、4例疾病稳定（NC，22%）、1例疾病进展（EP，6%）和4例疾病死亡（ED，22%）。这意味着缓解率为50%，中位生存时间为10个月。我们已按照精心制定的方案启动了一项II期研究。
