环磷酰胺、阿霉素和依托泊苷静脉输注联合去羟肌苷及非格司亭治疗人类免疫缺陷病毒相关非霍奇金淋巴瘤的初步试验

Pilot trial of infusional cyclophosphamide, doxorubicin, and etoposide plus didanosine and filgrastim in patients with human immunodeficiency virus-associated non-Hodgkin's lymphoma.

作者信息

Sparano J A, Wiernik P H, Hu X, Sarta C, Schwartz E L, Soeiro R, Henry D H, Mason B, Ratech H, Dutcher J P

机构信息

Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.

出版信息

J Clin Oncol. 1996 Nov;14(11):3026-35. doi: 10.1200/JCO.1996.14.11.3026.

DOI:10.1200/JCO.1996.14.11.3026

PMID:8918501

Abstract

PURPOSE

To determine the following: (1) the feasibility of combining the antiretroviral didanosine (ddl) with a 96-hour continuous intravenous (IV) infusion of cyclophosphamide (800 mg/m2), doxorubicin (50 mg/m2), and etoposide (240 mg/m2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection; (2) the effect of ddl on CDE-induced myelosuppression and CD4 lymphopenia; and (3) the effect of CDE on serum p24 antigen and quantitative HIV blood cultures.

METHODS

Twenty-five patients with HIV-related NHL received CDE every 28 or more days. Consecutive patients were assigned in an alternating fashion to group A (ddl given at a standard dose during cycles one, two, five, and six) or group B (ddl given during cycles three, four, five, and six).

RESULTS

ddl use was associated with less leukopenia (mean nadir, 3.33 v 1.49 x 10(3)/microL; p = .03), neutropenia (2.38 v 1.07 x 10(3)/microL; p = .03), and thrombocytopenia (76 v 48 x 10(3)/microL; p = .059), and fewer RBC (1.6 v 3.1 per cycle; p < .01) and platelet transfusions (0.7 v 1.5 per cycle; p < .01), but had no significant effect on CD4 lymphopenia. Furthermore, lymphomatous bone marrow involvement and low CD4 count were associated with significantly greater myelosuppression. Although there was no substantial change in serum p24 antigen, the HIV blood culture became quantitatively more positive or converted from negative to positive in seven patients (64%). Complete response (CR) occurred in 58% of patients (95% confidence interval, 38% to 78%), median CR duration exceeded 18 months, tumor-related mortality was 20%, and median survival was 18.4 months.

CONCLUSION

Our results suggest that the CDE and filgrastim regimen is tolerable and effective for patients with HIV-associated NHL, and that combination with ddl is feasible and may result in less myelosuppression.

摘要

目的

确定以下几点：（1）对于合并人类免疫缺陷病毒（HIV）感染的非霍奇金淋巴瘤（NHL）患者，将抗逆转录病毒药物去羟肌苷（ddI）与环磷酰胺（800mg/m²）、阿霉素（50mg/m²）和依托泊苷（240mg/m²）（CDE）进行96小时持续静脉输注并联合非格司亭的可行性；（2）ddI对CDE诱导的骨髓抑制和CD4淋巴细胞减少的影响；（3）CDE对血清p24抗原和HIV定量血培养的影响。

方法

25例HIV相关NHL患者每28天或更长时间接受一次CDE治疗。连续的患者交替分配到A组（在第1、2、5和6周期给予标准剂量的ddI）或B组（在第3、4、5和6周期给予ddI）。

结果

使用ddI与白细胞减少（平均最低点，3.33对1.49×10³/μL；p = 0.03）、中性粒细胞减少（2.38对1.07×10³/μL；p = 0.03）和血小板减少（76对48×10³/μL；p = 0.059）的发生率较低相关，红细胞输注（每周期1.6对3.1；p < 0.01）和血小板输注次数较少（每周期0.7对1.5；p < 0.01），但对CD4淋巴细胞减少无显著影响。此外，淋巴瘤骨髓受累和低CD4计数与明显更严重的骨髓抑制相关。虽然血清p24抗原无实质性变化，但7例患者（64%）的HIV血培养在定量上变得更阳性或从阴性转为阳性。58%的患者出现完全缓解（CR）（95%置信区间，38%至78%），CR的中位持续时间超过18个月，肿瘤相关死亡率为20%，中位生存期为18.4个月。