Department of Medical Oncology, University of Southern California Norris Cancer Center, Los Angeles, CA 90033, USA.
Am J Clin Oncol. 2011 Feb;34(1):27-31. doi: 10.1097/COC.0b013e3181cae766.
The primary objective of this study was to determine the maximum tolerated dose (MTD) of pegylated liposomal doxorubicin (PLD) and docetaxel (T) administered in 4 week cycles in patients with advanced solid tumors.
Patients were treated with intravenous PLD on day 1 and T on days 1, 8, and 15. Once the MTD was reached the schedule of PLD was changed to days 1 and 15 to explore an alternative and potentially more manageable dosing schedule.
Thirty-two patients were enrolled. A total of 106 cycles (median, 2 cycles; range, <1-13 cycles) of chemotherapy were administered. Three patients experienced dose-limiting toxicities which were stomatitis, anorexia, esophagitis, neutropenic fever, fatigue, and muscular weakness. When PLD was given on day 1, the MTD was PLD 33 mg/m and T 30 mg/m. MTD was not reached when PLD was administered on days 1 and 15: only 1 of 6 patients treated with PLD 20 mg/m and T 30 mg/m developed dose-limiting toxicities. The most common grade 3 or 4 hematologic toxicity was grade 3 neutropenia in 5 patients and grade 4 in 5. Two patients developed neutropenic fever. The most common grade 3 or 4 nonhematologic toxicity was grade 3 fatigue in 9 patients and grade 4 in 1. There was 1 confirmed PR, 2 unconfirmed PRs, and 12 patients with SD.
This combination of PLD and T was found to be feasible and tolerable. The recommended dose for phase II studies is PLD 20 mg/m on days 1 and 15 and T 35 mg/m on days 1, 8, and 15.
本研究的主要目的是确定在接受过治疗的晚期实体瘤患者中，每 4 周给予聚乙二醇化脂质体阿霉素（PLD）和多西他赛（T）的最大耐受剂量（MTD）。
患者接受静脉注射 PLD 第 1 天和 T 第 1、8 和 15 天。一旦达到 MTD，PLD 的方案就改为第 1 天和第 15 天，以探索一种替代的、潜在更易于管理的给药方案。
共招募了 32 名患者。共给予了 106 个周期（中位数，2 个周期；范围，<1-13 个周期）的化疗。有 3 名患者出现剂量限制毒性，包括口腔炎、厌食症、食管炎、中性粒细胞发热、疲劳和肌肉无力。当 PLD 在第 1 天给药时，MTD 为 PLD 33mg/m 和 T 30mg/m。当 PLD 在第 1 天和第 15 天给药时，MTD 未达到：仅在 6 名接受 PLD 20mg/m 和 T 30mg/m 治疗的患者中 1 名发生剂量限制毒性。最常见的 3 级或 4 级血液学毒性是 5 名患者发生 3 级中性粒细胞减少症和 5 名患者发生 4 级中性粒细胞减少症。2 名患者发生中性粒细胞发热。最常见的 3 级或 4 级非血液学毒性是 9 名患者发生 3 级疲劳和 1 名患者发生 4 级疲劳。有 1 例确认的 PR，2 例未确认的 PR 和 12 例患者疾病稳定。
本研究发现 PLD 和 T 联合使用是可行且耐受的。Ⅱ期研究的推荐剂量为 PLD 20mg/m 第 1 天和第 15 天，T 35mg/m 第 1、8 和 15 天。
