聚乙二醇脂质体阿霉素在CHOP方案治疗侵袭性非霍奇金淋巴瘤中的Ⅰ期剂量递增试验的安全性探索

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/m(2), 35 mg/m(2), 40 mg/m(2), 45 mg/m(2) 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/m(2) D1), vincristine (1.4 mg/m(2) 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/m(2), 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/m(2), 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/m(2).