Ross S R, McTavish D, Faulds D
Adis International Limited, Auckland, New Zealand.
Drugs. 1993 May;45(5):737-59. doi: 10.2165/00003495-199345050-00009.
Fludarabine is a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Noncomparative studies have shown response rates in patients with chronic lymphocytic leukaemia (CLL) that appear to be at least equivalent to those achieved with conventional therapy. Prolymphocytic leukaemia, a form of CLL which is often resistant to conventional chemotherapy, has also responded to treatment with fludarabine. Fludarabine combined with prednisone has also induced good response rates in patients with CLL but the limited data suggest that this does not offer an advantage over fludarabine alone. Several clinical trials have demonstrated a good cytoreductive response in patients with advanced, low grade non-Hodgkin's lymphoma, particularly that of follicular histology. Preliminary evidence indicates fludarabine in combination with cytarabine has therapeutic activity as salvage therapy in patients with acute leukaemia. Myelosuppression has been the major dose-limiting adverse effect reported in clinical trials of fludarabine. A reduction in CD4+ cell count may be associated with the increased incidence of fever and opportunistic infections in fludarabine recipients. Nausea and vomiting have also been commonly reported, but these are generally mild to moderate in severity. Reversible neurotoxicity has also been occasionally reported. Thus, fludarabine appears to offer a viable alternative to currently used treatments in CLL and low grade non-Hodgkin's lymphoma. Other potential areas of use for fludarabine include acute leukaemias. Waldenstrom's macroglobulinaemia and mycosis fungoides. However, trials of fludarabine in comparison with currently used therapies and also in combination with other antineoplastic agents are required to fully define its role in the treatment of lymphoid malignancies. In addition, because relapse in these diseases is common, long term trials assessing improvement in survival duration and quality of life would be of value.
氟达拉滨是一种氟化嘌呤类似物，在淋巴增生性恶性肿瘤中具有抗肿瘤活性。非对照研究表明，慢性淋巴细胞白血病（CLL）患者的缓解率似乎至少与传统疗法相当。幼淋巴细胞白血病是CLL的一种形式，通常对传统化疗耐药，但也对氟达拉滨治疗有反应。氟达拉滨联合泼尼松在CLL患者中也诱导出了良好的缓解率，但有限的数据表明，这并不比单独使用氟达拉滨有优势。几项临床试验表明，晚期低度非霍奇金淋巴瘤患者，尤其是滤泡组织学类型的患者，有良好的细胞减灭反应。初步证据表明，氟达拉滨联合阿糖胞苷作为急性白血病患者的挽救治疗具有治疗活性。骨髓抑制是氟达拉滨临床试验中报告的主要剂量限制性不良反应。CD4 + 细胞计数减少可能与氟达拉滨接受者发热和机会性感染的发生率增加有关。恶心和呕吐也经常被报告，但一般严重程度为轻至中度。偶尔也有可逆性神经毒性的报告。因此，氟达拉滨似乎是CLL和低度非霍奇金淋巴瘤目前治疗方法的可行替代方案。氟达拉滨的其他潜在应用领域包括急性白血病、华氏巨球蛋白血症和蕈样肉芽肿。然而，需要进行氟达拉滨与目前使用的疗法比较以及与其他抗肿瘤药物联合使用的试验，以充分确定其在淋巴恶性肿瘤治疗中的作用。此外，由于这些疾病的复发很常见，评估生存时间和生活质量改善情况的长期试验将很有价值。
