摘要目的 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(750mg/m2第1天)、长春新碱(1.4mg/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l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.

abstractsObjective To explore the maximum tolerated dose ofpegylated 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.