Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Cancer Chemother Pharmacol. 2012 Nov;70(5):755-61. doi: 10.1007/s00280-012-1919-6. Epub 2012 Aug 9.
To determine the safety, the maximal tolerated dose, and to assess for any clinical activity of pomalidomide given to patients with advanced solid tumors.
Patients with incurable solid tumors were enrolled. Two different dosing schedules were explored. In Cohort A patients were given pomalidomide once daily for 21 days followed by a 7 day rest. For Cohort B additional patients were recruited to receive pomalidomide given once daily for 28 consecutive days. Dose-limiting toxicity was defined as ≥grade 3 non-hematological toxicity that occurs during cycle 1 and that does not resolve to ≤grade 1 by day 35. Subjects must have received optimal symptomatic treatment for ≥grade 3 nausea, vomiting, or diarrhea to be considered a DLT. Grade 4 transaminitis was considered to be a DLT while grade 3 transaminitis must be present >7 days to be a DLT. Grade 3 febrile neutropenia was considered a DLT. Grade 4 neutropenia, without a fever, was a DLT if the neutropenia did not improve to ≤grade 1 by day 35 of cycle one. Platelet count ≤25,000/mm(3) must improve to ≥75,000/mm(3) by day 35 of cycle one in order not to be considered a DLT. If a patient did not complete one cycle of therapy, for reasons other than a DLT, a replacement subject was added to the same cohort level.
A total of 40 patients were enrolled. In Cohort A, three patients received pomalidomide at 5 mg daily without any significant toxicity. Two patients in the 10 mg cohort experienced dose-limiting toxicities of two episodes of grade 3 dyspnea and one grade 4 neutropenia. Six patients were then enrolled at the 7 mg daily of pomalidomide, and no dose-limiting events were observed. In Cohort B, 29 patients were enrolled and the maximal tolerated dose was 4 mg once daily. Stable disease in a variety of tumors was observed.
Pomalidomide was well tolerated and the recommended phase II dosing schedules are 7 mg daily given for 21 days followed by a 7-day rest or pomalidomide 4 mg given on an uninterrupted daily schedule.
确定给予晚期实体瘤患者来那度胺的安全性、最大耐受剂量，并评估任何临床活性。
入组无法治愈的实体瘤患者。探索了两种不同的给药方案。在队列 A 中，患者每天接受来那度胺治疗 21 天，然后休息 7 天。对于队列 B，招募了更多的患者接受每天一次连续 28 天的来那度胺治疗。剂量限制性毒性定义为在第 1 周期内发生≥3 级非血液学毒性，且在第 35 天前未恢复至≤1 级。对于≥3 级恶心、呕吐或腹泻，必须接受最佳对症治疗，才能被认为是剂量限制毒性（DLT）。4 级转氨酶升高被认为是剂量限制毒性，而 3 级转氨酶升高>7 天才能被认为是剂量限制毒性。3 级发热性中性粒细胞减少症被认为是剂量限制毒性。在第 1 周期的第 35 天，中性粒细胞计数未恢复至≤1 级的情况下，无发热的 4 级中性粒细胞计数也被认为是剂量限制毒性。血小板计数≤25,000/mm(3)的患者，必须在第 1 周期的第 35 天之前提高至≥75,000/mm(3)，才能不被认为是剂量限制毒性。如果患者由于非剂量限制毒性以外的原因未完成一个周期的治疗，则在下一个队列水平添加替换受试者。
共入组 40 例患者。在队列 A 中，3 例患者接受 5mg 来那度胺治疗，无明显毒性。10mg 队列中有 2 例患者发生 2 次 3 级呼吸困难和 1 例 4 级中性粒细胞减少症的剂量限制毒性。然后，6 例患者接受 7mg 来那度胺治疗，未观察到剂量限制事件。在队列 B 中，入组 29 例患者，最大耐受剂量为 4mg 每日一次。观察到多种肿瘤的疾病稳定。
来那度胺耐受性良好，推荐的 II 期给药方案为 21 天每日 7mg 治疗，随后休息 7 天，或每日不间断给予来那度胺 4mg。
