Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia

被引:28
作者
Cortes, J [1 ]
Estey, E [1 ]
Beran, M [1 ]
O'Brien, S [1 ]
Giles, F [1 ]
Koller, C [1 ]
Keating, M [1 ]
Kantarjian, H [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
关键词
topotecan; cyclophosphamide; cytarabine; acute leukemia; salvage;
D O I
10.3109/10428190009148395
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, when topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m(2) every 12 hours given on days 1 to 3; topotecan 1.25 mg/m(2)/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m(2) over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (KI; met all criteria for CR except for platelets < 100x10(9)/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%). and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.
引用
收藏
页码:479 / 484
页数:6
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