Sanborn Sharon L, Cooney Matthew M, Dowlati Afshin, Brell Joanna M, Krishnamurthi Smitha, Gibbons Joseph, Bokar Joseph A, Nock Charles, Ness Anne, Remick Scot C
Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, 11100 Euclid Avenue, Lakeside 1200, Cleveland, OH 44106, USA.
Invest New Drugs. 2008 Aug;26(4):355-62. doi: 10.1007/s10637-008-9137-0. Epub 2008 May 10.
Pre-clinical models have demonstrated the benefit of metronomic schedules of cytotoxic chemotherapy combined with anti-angiogenic compounds. This trial was undertaken to determine the toxicity of a low dose regimen using docetaxel and thalidomide.
Patients with advanced solid tumors were enrolled. Thalidomide 100mg twice daily was given with escalating doses of docetaxel from 10 to 30 mg/m(2)/week. One cycle consisted of 12 consecutive weeks of therapy. The maximal tolerated dose (MTD) was defined as the dose of thalidomide along with docetaxel that caused < or =grade 1 non-hematologic or < or =grade 2 hematologic toxicity for cycle one.
Twenty-six patients were enrolled. Dose-limiting toxicities (DLTs) were bradycardia, fatigue, fever, hyperbilirubinemia, leukopenia, myocardial infarction, and neutropenia. Prolonged freedom from disease progression was observed in 44.4% of the evaluable patients.
This anti-angiogenic regimen was well tolerated and demonstrated clinical benefit. The recommended phase II dosing schedule is thalidomide 100 mg twice daily with docetaxel 25 mg/m(2)/week.
临床前模型已证明细胞毒性化疗与抗血管生成化合物的节拍式给药方案具有益处。本试验旨在确定使用多西他赛和沙利度胺的低剂量方案的毒性。
纳入晚期实体瘤患者。沙利度胺每日两次，每次100mg，同时多西他赛剂量从10mg/m²/周递增至30mg/m²/周。一个周期包括连续12周的治疗。最大耐受剂量（MTD）定义为沙利度胺与多西他赛的剂量组合，该组合在第一个周期引起≤1级非血液学毒性或≤2级血液学毒性。
26例患者入组。剂量限制性毒性（DLTs）为心动过缓、疲劳、发热、高胆红素血症、白细胞减少、心肌梗死和中性粒细胞减少。44.4%的可评估患者观察到疾病进展的长期缓解。
该抗血管生成方案耐受性良好并显示出临床益处。推荐的II期给药方案是沙利度胺每日两次，每次100mg，多西他赛25mg/m²/周。
