title: Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia.
abstract: 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, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 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 (HI; 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.
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. jcortes@notes.mdacc.tmc.edu
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: E
authors.initials: E
authors.lastname: Estey
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: F
authors.initials: F
authors.lastname: Giles
authors.forename: C
authors.initials: C
authors.lastname: Koller
authors.forename: M
authors.initials: M
authors.lastname: Keating
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D012008:Recurrence; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D019772:Topotecan; D003520:Cyclophosphamide