Adkins J C, Peters D H, Markham A
Adis International Limited, Auckland, New Zealand.
Drugs. 1997 Jun;53(6):1005-37. doi: 10.2165/00003495-199753060-00007.
Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.
氟达拉滨是一种抗肿瘤药物，已在多种淋巴增殖性恶性肿瘤患者中进行了研究。慢性淋巴细胞白血病（CLL）比较研究的临床证据表明，在既往接受过治疗或未接受过化疗的患者中，氟达拉滨至少与环磷酰胺、阿霉素和泼尼松（CAP）或环磷酰胺、长春新碱、阿霉素和泼尼松（CHOP）一样有效，在未接受过化疗的患者中，就缓解率、缓解持续时间和生存率而言，氟达拉滨比苯丁酸氮芥显著更有效。基于氟达拉滨的联合疗法治疗CLL患者也报告了有前景的结果。此外，氟达拉滨与阿糖胞苷序贯治疗在急性白血病治疗中显示出良好疗效，氟达拉滨单药治疗及联合治疗在低度非霍奇金淋巴瘤中也有良好疗效。在淋巴浆细胞样淋巴瘤患者以及少数皮肤T细胞淋巴瘤、T细胞来源的CLL或幼淋巴细胞白血病患者中报告了良好的细胞减灭反应。最近的数据也支持在接受外周血干细胞或骨髓移植的患者中使用氟达拉滨，要么作为非清髓性预处理方案的组成部分，要么用于实现微小残留病。氟达拉滨的耐受性与CAP相似，最常见的不良事件是粒细胞减少、血小板减少、贫血和感染。与CAP治疗相比，氟达拉滨治疗时脱发和恶心/呕吐似乎较少见，尽管氟达拉滨治疗时免疫性血细胞减少的发生更常见。有报告称氟达拉滨有严重神经毒性，但这大多局限于高剂量使用时。因此，临床经验表明，氟达拉滨是晚期CLL二线治疗的一种有效且一般耐受性良好的抗肿瘤药物。比较研究的最新数据也支持在未接受过化疗的CLL患者治疗中更早使用氟达拉滨。此外，现有研究结果越来越凸显氟达拉滨在急性白血病和低度NHL以及可能的其他淋巴增殖性疾病治疗中的重要未来作用，特别是当用作联合化疗的组成部分时。
