Ozer H, Anderson J R, Peterson B A, Budman D R, Cooper M R, Kennedy B J, Silver R T, Henderson E S, Duggan D B, Barcos M
Department of Medicine, University of North Carolina, Chapel Hill 27599-7305.
Med Pediatr Oncol. 1994;22(4):228-35. doi: 10.1002/mpo.2950220403.
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 rIFN alpha 2b (2 x 10(6) IU/m2 s.c. tiw) and cyclophosphamide (100 mg/m2 per 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.
滤泡性非霍奇金淋巴瘤（NHL）是在I期和II期临床试验中被证明对α干扰素常有反应的肿瘤之一。此外，有数据表明，在多种肿瘤的动物模型中，α干扰素与烷化剂显示出协同抗肿瘤活性。基于这些数据，癌症与白血病B组（CALGB）开展了一项II期试点研究，联合使用干扰素rIFNα2b（2×10⁶IU/m²皮下注射，每周3次）和环磷酰胺（100mg/m²每日口服），最终目的是将该联合方案与单独口服环磷酰胺相比较，作为滤泡性淋巴瘤的长期治疗方法进行研究。105例符合条件的晚期III期或IV期患者，经病理诊断为国际工作分类法B或C组织学类型，进入CALGB 8553研究以确定该联合方案的毒性和缓解率。既往接受过化疗的患者（32例）和未接受过化疗的患者（73例）均纳入研究。对于未接受过化疗的患者，联合方案的总缓解率为86%，接受过化疗的患者中有58%达到完全缓解。接受过化疗的患者总缓解率为62%，只有25%达到完全缓解。未接受过化疗的患者的完全缓解与无B症状、良好的身体状况呈正相关，与滤泡性混合小裂细胞和大细胞组织学（IWF C）的组织学亚型呈负相关；在既往接受过化疗的患者中只有身体状况与缓解显著相关。估计未接受化疗的患者5年生存率为63%，既往接受过化疗的患者为39%。环磷酰胺和干扰素α联合方案治疗期间经历中的最大毒性主要与骨髓抑制有关。67%未接受过化疗的患者和65%接受过化疗的患者出现严重白细胞减少，而这些患者中有6%-31%出现严重血小板减少和贫血。非骨髓抑制性毒性较少见。这些缓解率与CALGB之前一项以口服环磷酰胺作为单一药物的试验所取得的缓解率相似，尽管严重骨髓毒性从单一药物治疗时不到10%的患者增加到了约60%的患者。当仔细监测外周血细胞计数时，以这种方式给予的α干扰素和环磷酰胺联合方案是安全的。目前正在进行该方案与口服环磷酰胺比较的随机研究。
