多柔比星、长春新碱、依托泊苷联合环磷酰胺及泼尼松的输注化疗方案（I-CHOPE）用于难治性弥漫性侵袭性非霍奇金淋巴瘤的II期研究：癌症与白血病B组研究（CALGB 9255）

Phase II study of infusional chemotherapy with doxorubicin, vincristine and etoposide plus cyclophosphamide and prednisone (I-CHOPE) in resistant diffuse aggressive non-Hodgkin's lymphoma: CALGB 9255. Cancer and Leukemia Group B.

作者信息

Lichtman S M, Niedzwiecki D, Barcos M, Carlisle T L, Cooper M R, Johnson J L, Peterson B A

机构信息

Don Monti Division of Oncology, North Shore University Hospital-NYU School of Medicine, Manhasset, New York 11030, USA.

出版信息

Ann Oncol. 2000 Sep;11(9):1141-6. doi: 10.1023/a:1008395400069.

DOI:10.1023/a:1008395400069

PMID:11061609

Abstract

BACKGROUND

Patients with resistant diffuse aggressive non-Hodgkin's lymphoma (DA-NHL) have a poor prognosis. Studies have suggested infusional therapy may be beneficial.

PATIENTS AND METHODS

This trial used an infusional regimen called I-CHOPE in resistant patients who had previously received only bolus CHOPE or CHOP regimen. Resistance was defined as: a) primary refractory disease, b) progression on therapy, c) partial response, d) complete remission lasting less than one year. Eligibility criteria included a diagnosis of DA-NHL (IWF E-H), no prior irradiation and adequate organ function.

RESULTS

Thirty-seven patients were entered and twenty-nine were eligible. Reasons for ineligibility were incorrect histology (5) and other (3). The median age was 57 years (range 29-81) with 21 males. The performance status scores were: 0 (12 patients); 1 (9 patients); 2 (8 patients). Prior therapy consisted of standard CHOP (26 patients), bolus CHOPE (2 patients), high dose CHOP (1 patient). Therapy consisted of a 120 hour continuous intravenous infusion of doxorubicin 10 mg/m2/day, vincristine 0.28 mg/m2/day (maximum 0.4 mg/day), and etoposide 48 mg/m2/day. Cyclophosphamide 750 mg/m2 was given as an i.v. bolus day 6 and prednisone was given at 100 mg/day p.o. on days 1-5. G-CSF was allowed for myelosuppression. The overall response rate was 48% (CR 17%; PR 31%). Freedom from progression was 24% at six months and 8% at one year. Survival was 69% at six months and 40% at one year. In an exploratory analysis a prior CR or PR predicted response to I-CHOPE. Twelve of sixteen patients who had a CR/PR on previous therapy responded while two of thirteen who had no prior response, responded to I-CHOPE (P = 0.003). The toxicity was tolerable with grade 3-4 hematologic toxicity being leucopenia 94% and thrombocytopenia 41%. The grade 3-4 non-hematologic toxicities were infection in 28%, phlebitis in 11%, and stomatitis in 15%.

CONCLUSIONS

I-CHOPE can induce responses in this group of patients with a poor prognosis, but most were seen in those who had previously had a response to bolus chemotherapy.

摘要

背景

难治性弥漫性侵袭性非霍奇金淋巴瘤（DA-NHL）患者预后较差。研究表明输注疗法可能有益。

患者与方法

本试验对先前仅接受过单次CHOPE或CHOP方案治疗的难治性患者使用一种名为I-CHOPE的输注方案。难治性定义为：a）原发性难治性疾病，b）治疗期间病情进展，c）部分缓解，d）完全缓解持续时间少于一年。入选标准包括DA-NHL（IWF E-H）诊断、无既往放疗史且器官功能良好。

结果

37例患者入组，29例符合条件。不符合条件的原因是组织学诊断错误（5例）和其他原因（3例）。中位年龄为57岁（范围29 - 81岁），男性21例。体能状态评分如下：0分（12例患者）；1分（9例患者）；2分（8例患者）。既往治疗包括标准CHOP方案（26例患者）、单次CHOPE方案（2例患者）、大剂量CHOP方案（1例患者）。治疗方案包括阿霉素10 mg/m²/天、长春新碱0.28 mg/m²/天（最大0.4 mg/天）和依托泊苷48 mg/m²/天持续静脉输注120小时。环磷酰胺750 mg/m²于第6天静脉推注，泼尼松于第1 - 5天口服100 mg/天。允许使用粒细胞集落刺激因子（G-CSF）治疗骨髓抑制。总缓解率为48%（完全缓解17%；部分缓解31%）。6个月时无进展生存率为24%，1年时为8%。6个月时生存率为69%，1年时为40%。在一项探索性分析中，先前的完全缓解或部分缓解可预测对I-CHOPE的反应。先前治疗有完全缓解/部分缓解的16例患者中有12例对I-CHOPE有反应，而先前无反应的13例患者中有2例对I-CHOPE有反应（P = 0.003）。毒性可耐受，3 - 4级血液学毒性为白细胞减少94%，血小板减少41%。3 - 4级非血液学毒性为感染28%、静脉炎11%、口腔炎15%。