Ribrag V, Koscielny S, Vantelon J M, Fermé C, Rideller K, Carde P, Bourhis J H, Munck J N
Department de Médecine, Institut Gustave-Roussy, 39 Rue C Desmoulins, 94805 Villejuif, France.
Leuk Lymphoma. 2003 Sep;44(9):1529-33. doi: 10.3109/10428190309178775.
CPT11, a camptothecin analogue, is a specific DNA topoisomerase I inhibitor, with activity in tumor cell lines with MDR expression. CPT11 has a broad spectrum of activity in solid tumors (especially in colorectal, gastric and small cell lung cancers). Early reports have shown that CPT11 could be active in non-Hodgkin's lymphomas (NHL) with low-dose schedules. To further evaluate the efficacy and toxicity of CPT11 in patients with refractory or relapsed NHLs, we conducted a phase II trial with escalated doses.
From 04/98 to 05/01, 28 patients with NHL were enrolled.
M/F 21/7; median age: 56 years (range 28-72); Ann Arbor stage at the time of the study I/II and III/IV in 6 and 21 patients, respectively. Sixteen patients had refractory disease when they were enrolled in this phase II study and 8 patients were previously treated with high-dose therapy and stem-cell transplantation. CPT11 was administrated at the doses of 350 mg/m2 every 3 weeks. Six courses were given in patients who achieved CR, PR or stable disease. Patients were evaluated every 2 courses. If no grade II or more toxicity was observed after the first course, escalated dose (500 mg/m2) was then undertaken.
19/28 patients received more than 2 courses of CPT11 and were evaluated for response. Nine patients received one course of therapy because of either progressive disease (n = 6), toxicity (n = 2) or refusal (n = 1). Ten patients received escalated dose (500 mg/m2). Complete remission and partial was achieved in 2/19 patients, stable disease in 7/19, and progressive disease in 10/19 patients. Median duration of responses was short (3 months, range 1-8 months). Seventy-five courses were evaluated for toxicity according to the WHO criteria. Diarrhea grade 2 or 3 occurred in 9/75 courses; cholinergic syndrome grade 2 in 3/75 courses; nausea grade 3 in 7/75 courses. Hematological toxicity: leucopenia grade 3 or 4 in 21/75 courses; thrombocytopenia grade 3 in 8/75 courses; infectious episodes grade 2 or 3 in 7/75 courses. In 2/7 courses with escalated doses, grade I/IV neutropenia occurred withoutother major toxicity.
CPT11 has low activity in heavily pretreated NHLs. Responses were of short duration.
CPT11是一种喜树碱类似物，是一种特异性DNA拓扑异构酶I抑制剂，对表达多药耐药（MDR）的肿瘤细胞系具有活性。CPT11在实体瘤（尤其是结直肠癌、胃癌和小细胞肺癌）中具有广泛的活性。早期报告显示，低剂量方案的CPT11在非霍奇金淋巴瘤（NHL）中可能具有活性。为了进一步评估CPT11对难治性或复发性NHL患者的疗效和毒性，我们进行了一项剂量递增的II期试验。
从1998年4月至2001年5月，纳入了28例NHL患者。
男/女为21/7；中位年龄：56岁（范围28 - 72岁）；研究时Ann Arbor分期I/II期6例，III/IV期21例。16例患者在进入本II期研究时患有难治性疾病，8例患者先前接受过高剂量治疗和干细胞移植。CPT11每3周以350 mg/m²的剂量给药。达到完全缓解（CR）、部分缓解（PR）或疾病稳定的患者给予6个疗程。每2个疗程对患者进行评估。如果在第一个疗程后未观察到II级或更高级别的毒性，则采用递增剂量（500 mg/m²）。
19/28例患者接受了超过2个疗程的CPT11治疗并进行了疗效评估。9例患者因疾病进展（n = 6）、毒性（n = 2）或拒绝（n = 1）仅接受了1个疗程的治疗。10例患者接受了递增剂量（500 mg/m²）。19例患者中2例达到完全缓解，7例疾病稳定，10例疾病进展。缓解的中位持续时间较短（3个月，范围1 - 8个月）。根据世界卫生组织（WHO）标准对75个疗程进行了毒性评估。75个疗程中有9个出现2级或3级腹泻；3个出现2级胆碱能综合征；7个出现3级恶心。血液学毒性：75个疗程中有21个出现3级或4级白细胞减少；8个出现3级血小板减少；7个出现2级或3级感染发作。在2个递增剂量的疗程中，出现了I/IV级中性粒细胞减少，无其他主要毒性。
CPT11在经过大量治疗的NHL中活性较低。缓解持续时间较短。
