Combination trial of subcutaneous recombinant alpha 2 b interferon and oral cyclophosphamide in follicular low-grade non-Hodgkin's lymphoma.
Combination trial of subcutaneous recombinant alpha 2 b interferon and oral cyclophosphamide in follicular low-grade non-Hodgkin's lymphoma.
复制标题
皮下重组α2b干扰素和口服环磷酰胺联合治疗滤泡性低度非霍奇金淋巴瘤的试验。
DOI：
10.1002/mpo.2950220403
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Barcos,M
中科院分区：
文献类型：
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作者：
Ozer,H;Anderson,JR;Peterson,BA;Budman,DR;Cooper,MR;Kennedy,BJ;Silver,RT;Henderson,ES;Duggan,DB;Barcos,M
在I期和II期临床试验中，滤泡性非霍奇金淋巴瘤（NHL）已被证明对α干扰素有频繁反应。此外，有数据表明，在许多肿瘤的动物模型中，α -干扰素显示出与烷基化剂的协同抗肿瘤活性。基于这些数据，Cancer and Leukemia Group B （CALGB）开展了干扰素rlFNα2b （2 × 106IU/m2s.c）联合治疗的II期中试研究。与单独口服环磷酰胺相比，Tiw)和环磷酰胺（100mg /m2 /天口服）的最终目的是研究该组合作为滤泡性淋巴瘤的长期治疗方法。105例病理诊断为国际工作配方B或C组织学的晚期III期或IV期合格患者进入CALGB 8553，以确定联合用药的毒性和反应率。既往接受化疗的患者（32例）和未接受化疗的患者（73例）均被纳入研究。对于先前没有化疗的患者，联合方案的总缓解率为86%，其中58%的化疗患者达到完全缓解。化疗患者的总缓解率为62%，完全缓解率仅为25%。未接受化疗的患者的完全缓解与无B症状和良好的表现状态呈正相关，与滤泡混合小裂细胞和大细胞组织学（IWF C）的组织学亚型负相关；在先前接受过化疗的患者中，只有表现状态与反应显著相关。据估计，未接受化疗的患者5年生存率为63%，而以前接受过化疗的患者5年生存率为39%。在环磷酰胺和干扰素联合治疗期间，最大的毒性主要与骨髓抑制有关。67%未接受化疗的患者和65%接受化疗的患者出现了严重的白细胞减少症，而这些患者中有6.31%发生了严重的血小板减少症和贫血。非骨髓抑制性毒性较少见。这些反应率与先前的CALGB试验中口服环磷酰胺作为单一药物的反应率相似，尽管严重髓毒性从单一药物治疗的不到10%增加到大约60%。在仔细监测外周血计数时，以这种方式联合使用干扰素和环磷酰胺是安全的。目前正在进行该方案与口服环磷酰胺比较的随机研究。©1994 Wiley‐Liss, Inc。
The follicular non‐Hodgkin's lymphomas (NHL) have been among those tumors demonstrated to show frequent responses to alpha interferon in phase I and II clinical trials. In addition, there are data suggesting that alpha interferon demonstrates synergistic antitumor activity with alkylating agents in animal models for a number of tumors. Based on these data, Cancer and Leukemia Group B (CALGB) undertook a phase II pilot study of the combination of interferon rlFNα2b (2 × 106IU/m2s.c. tiw) and cyclophosphamide (100 mg/m2per day orally) with the ultimate purpose of examining this combination as long‐term therapy of follicular lymphoma in comparison to oral cyclophosphamide alone. One hundred five advanced stage III or IV eligible patients with pathologically diagnosed International Working Formulation B or C histology were entered on CALGB 8553 to determine toxicity and response rates to the combination. Both previously chemotherapy‐treated patients (32) and patients without prior chemotherapy (73) were entered on study. For patients without prior chemotherapy the overall response rate to the combination regimen was 86% with 58% of chemotherapy‐treated patients achieving complete response. Chemotherapy‐treated patients had a total response rate of 62% with only 25% complete responders. Complete responses in patients without prior chemotherapy were positively correlated with absence of B symptoms, and good performance status and negatively correlated with the histological subtype of follicular mixed small‐cleaved and large cell histology (IWF C); only performance status was significantly correlated with response in patients who had previously had chemotherapy. Survival at 5 years is estimated to be 63% for those without chemotherapy and 39% for those previously treated with chemotherapy patients. The maximum toxicities experienced during therapy with the combination regimen of cyclophosphamide and interferon alpha were primarily related to myelosuppression. Sixty‐seven percent of patients without prior chemotherapy and 65% of patients receiving prior chemotherapy experienced severe leukopenia while severe thrombocytopenia and anemia occurred in 6‐31% of these patients. Non‐myelosuppressive toxicities were less frequently seen. These response rates are similar to those achieved in a previous CALGB trial with oral cyclophosphamide as a single agent, although severe myelotoxicity was increased to approximately 60% of patients from less than 10% with the single‐agent therapy. The combination of alpha interferon and cyclophosphamide administered in this fashion is safe when peripheral counts are carefully monitored. Randomized studies of this regimen in comparison to oral cyclophosphamide are currently in progress. © 1994 Wiley‐Liss, Inc.