Objective: To explore the maximum tolerated dose of pegylated liposomal doxorubicin (PLD) in combination with cyclophosphamide, vincristine and prednisone as a modified CHOP regimen for aggressive non-Hodgkin lymphoma. Methods: Patients with newly diagnosed aggressive non-Hodgkin lymphoma were eligible for this trial. PLD was administered in cycle 1 and categorized into 4 dose level (30 mg/m2, 35 mg/m2, 40 mg/m2, 45 mg/m2 D1) according to a 3 + 3 approach for dose-escalation. Doxorubin was used in cycles 2-6. In this combination regimen, the doses of cyclophosphamide (750 mg/m2 D1), vincristine (1.4 mg/m2 D1, maximum dose of 2 mg) and prednisone (100 mg D1-5) were fixed. Toxicities of cycle 1 were documented. Results: Totally, 21 patients were enrolled in this trial. Among them, 15 patients had T-cell lymphoma and 6 had B-cell lymphoma. When the dose of PLD was escalated to the level of 45 mg/m2, 2 of 3 patients developed grade 3 mucositis, which met the criteria of dose-limiting toxicity. Therefore, the dose was de-escalated for one level. At the level of 40 mg/m2, only one among 12 patients had pneumonia and grade 4 neutropenia. In all dose levels, the grade 3/4 toxicities observed were neutropenia (13 cases, 61.9% ), mucositis (2 cases, 9.5% ), thrombocytopenia (1 case, 4.8%) and pneumonia (1 case, 4.8%). Conclusion: When combined with cyclophosphamide, vincristine and prednisone as a combination regimen, the maximum tolerated dose of PLD was 40 mg/m2.
目的: 探索聚乙二醇脂质体阿霉素（PLD）在联合环磷酰胺、长春新碱和泼尼松组成改良CHOP方案中的最大耐受剂量（MTD）。
方法: 研究纳入21例初治侵袭性非霍奇金淋巴瘤患者。患者第1个周期使用PLD，分为4个剂量水平（30、35、40、45 mg/m2第1天）按照3+3方法进行剂量递增，第2~6个周期使用阿霉素（50 mg/m2第1天）。而联合方案中环磷酰胺（750 mg/m2第1天）、长春新碱（1.4 mg/m2第1天，最大剂量不超过2 mg）和泼尼松（100 mg/d第1~5天）的剂量保持不变，仅统计第1个周期的不良反应。
结果: 21例患者中男14例，女7例，中位年龄49(25~67）岁。T细胞淋巴瘤15例，B细胞淋巴瘤6例。在PLD剂量递增至45 mg/m2剂量组时，3例患者中2例出现3级口腔黏膜炎，达到剂量限制性毒性，因此剂量下调一个等级。在40 mg/m2剂量组时，12例患者中仅有1例出现肺炎伴4级中性粒细胞下降。所有剂量组中，观察到的3~4级不良反应为中性粒细胞下降（13例，61.9%）、口腔黏膜炎（2例，9.5%）、血小板下降（1例，4.8%）和肺炎（1例，4.8%），经过抗感染、口腔护理、支持治疗后症状均可缓解。
结论: 在联合环磷酰胺、长春新碱和泼尼松治疗侵袭性非霍奇金淋巴瘤的治疗方案中，PLD的最大耐受剂量为40 mg/m2，不良反应经对症处理后症状可缓解。