Stathopoulos George P, Boulikas Teni, Kourvetaris Andreas, Stathopoulos John
First Oncology Department Errikos Dunant Hospital, Athens, Greece.
Anticancer Res. 2006 Mar-Apr;26(2B):1489-93.
Lipoxal is a liposomal oxaliplatin, which reduces the cytotoxic agent's adverse reactions without reducing effectiveness. Our objectives were to determine the adverse reactions, dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of lipoxal.
Twenty-seven patients with advanced disease of the gastrointestinal system were included in the study. All patients had been pretreated with standard chemotherapy according to established guidelines. At entry, all patients had recurrent or progressive disease (stage IV gastrointestinal cancers: colorectal, gastric and pancreatic). Six lipoxal dose levels (100 mg/m2, 150 mg/m2, 200 mg/m2, 250 mg/m2, 300 mg/m2 and 350 mg/m2) were set and at least 3 patients were included at each level. Eight patients were treated at 300 mg/m2 (MTD). The treatment was given once weekly for 8 weeks.
No serious side-effects were observed at the first 4 dose levels (100-250 mg/m2). At levels 5 and 6, mild myelotoxicity and nausea were observed. The most common adverse reaction was grade 2-3 peripheral neuropathy, observed in all 4 patients treated at 350 mg/m2. The 350 mg/m2 dose level was therefore considered as DLT and the 300 mg/m2 level as the MTD. Of the 27 patients, 3 achieved partial response and 18 had stable disease for 4 months, (range 2-9 months).
The most common toxicity was peripheral neuropathy at the 300 and 350 mg/m2 dose levels. Lipoxal was well-tolerated and greatly reduced all the other side-effects of oxaliplatin, especially myelotoxicity and gastrointestinal tract toxicities. These preliminary results showed adequate effectiveness in pretreated patients.
脂草酸铂是一种脂质体奥沙利铂，可在不降低疗效的情况下减少细胞毒性药物的不良反应。我们的目标是确定脂草酸铂的不良反应、剂量限制毒性（DLT）和最大耐受剂量（MTD）。
本研究纳入了27例晚期胃肠系统疾病患者。所有患者均按照既定指南接受过标准化化疗预处理。入组时，所有患者均患有复发或进展性疾病（IV期胃肠道癌症：结直肠癌、胃癌和胰腺癌）。设定了6个脂草酸铂剂量水平（100mg/m²、150mg/m²、200mg/m²、250mg/m²、300mg/m²和350mg/m²），每个水平至少纳入3例患者。8例患者接受了300mg/m²（MTD）治疗。治疗每周进行1次，共8周。
在前4个剂量水平（100 - 250mg/m²）未观察到严重副作用。在第5和第6水平，观察到轻度骨髓毒性和恶心。最常见的不良反应是2 - 3级周围神经病变，在所有接受350mg/m²治疗的4例患者中均有观察到。因此，350mg/m²剂量水平被视为DLT，300mg/m²水平被视为MTD。27例患者中，3例达到部分缓解，18例病情稳定4个月（范围2 - 9个月）。
在300和350mg/m²剂量水平，最常见的毒性是周围神经病变。脂草酸铂耐受性良好，大大降低了奥沙利铂的所有其他副作用，尤其是骨髓毒性和胃肠道毒性。这些初步结果表明对预处理患者有足够的疗效。
