Kath R, Blumenstengel K, Fricke H J, Höffken K
Klinik und Poliklinik für Innere Medizin II der Friedrich Schiller Universität Jena, Germany.
J Cancer Res Clin Oncol. 2001 Jan;127(1):48-54. doi: 10.1007/s004320000180.
Bendamustine, an alkylating agent without cross-resistance to cyclophosphamide is active in a variety of lymphoproliferative and other malignancies. In an open phase-II study we treated 23 patients with a median age of 62 years at study entry (43-86 years) with advanced, refractory or relapsed (Rai stage III n = 9, Rai stage IV n = 14) chronic lymphocytic leukemia (CLL) with bendamustine. At study entry, only 13 patients were chemotherapy-naive. The treatment schedule with bendamustine was as follows: for patients up to 70 years 60 mg/m2 for 5 days, for patients over 70 years 50 mg/m2 for 5 days, repetition at day 29. Remission criteria were used according to Cheson et al. (1996). All patients were evaluable for toxicity and 20 for response. An objective remission was achieved in 15/20 patients (75%), including six patients with complete remission (CR). Three of the complete responders had no chemotherapy prior to bendamustine. No change (NC) occurred in 5/20 patients (25%). Median overall survival after bendamustine treatment is 13.6 months (1-46 months) and 16.6 months (1-46 months) in patients responding to bendamustine. In total, 74 courses of bendamustine were applied. Therapy-related anemia and thrombocytopenia were rare. However, WHO grade III/IV leukocytopenia occurred in 38/74 cycles (51%), resulting in treatment-related mortality in 3/23 patients (13%). These patients were severely immunocompromised due to pretreatment or the underlying disease. As a corollary of the study, a general prophylactic antibiotic treatment (trimethoprim/ sulfamerazine) was instituted. A general feature was the decline of the CD4/CD8 ratio: mean before therapy: 1.36; after two courses: 0.98; after four courses: 0.6, as documented in all patients who received at least two courses of bendamustine (n = 12). All evaluable patients showed a decline in the CD4/8 ratio. However, this decline was not clearly related to an increased risk of infectious episodes. We observed mainly cutaneous allergic reactions (three WHO grade I; one WHO grade II) leading to a cessation of bendamustine treatment in 4/23 patients (18%). Bendamustine is highly effective in advanced or refractory CLL. In multiple pretreated or otherwise severely immunocompromised patients bendamustine might lead to additional immunosuppression with subsequent infectious complications.
苯达莫司汀是一种对环磷酰胺无交叉耐药性的烷化剂，对多种淋巴增殖性疾病及其他恶性肿瘤有效。在一项开放性II期研究中，我们用苯达莫司汀治疗了23例慢性淋巴细胞白血病（CLL）患者，研究入组时的中位年龄为62岁（43 - 86岁），均为晚期、难治性或复发性（Rai分期III期n = 9，Rai分期IV期n = 14）患者。研究入组时，只有13例患者未接受过化疗。苯达莫司汀的治疗方案如下：70岁及以下患者60mg/m²，连用5天；70岁以上患者50mg/m²，连用5天，在第29天重复给药。缓解标准依据Cheson等人（1996年）的标准。所有患者均可评估毒性，20例可评估疗效。20例患者中有15例（75%）达到客观缓解，其中6例完全缓解（CR）。3例完全缓解者在接受苯达莫司汀治疗前未接受过化疗。20例患者中有5例（25%）病情无变化（NC）。接受苯达莫司汀治疗后的中位总生存期为13.6个月（1 - 46个月），对苯达莫司汀有反应的患者为16.6个月（1 - 46个月）。共应用了74个疗程的苯达莫司汀。与治疗相关的贫血和血小板减少很少见。然而，WHO III/IV级白细胞减少发生在38/74个周期（51%），导致3/23例患者（13%）出现治疗相关死亡。这些患者因预处理或基础疾病而严重免疫功能低下。作为该研究的一个推论，开始了一般预防性抗生素治疗（甲氧苄啶/磺胺甲嘧啶）。一个普遍特征是CD4/CD8比值下降：治疗前平均为1.36；两个疗程后为0.98；四个疗程后为0.6，这在所有接受至少两个疗程苯达莫司汀治疗的患者（n = 12）中均有记录。所有可评估的患者CD4/8比值均下降。然而，这种下降与感染发作风险增加并无明显关联。我们主要观察到皮肤过敏反应（3例WHO I级；1例WHO II级），导致4/23例患者（18%）停止苯达莫司汀治疗。苯达莫司汀对晚期或难治性CLL非常有效。在多次预处理或其他严重免疫功能低下的患者中，苯达莫司汀可能导致额外的免疫抑制，随后出现感染并发症。
