title: Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia.
abstract: BACKGROUND
  Topoisomerase I inhibitors, like topotecan, have activity in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). 9-Nitro-camptothecin (9-NC) is a new oral topoisomerase inhibitor with a good safety profile. The aims of the current study were to evaluate the activity and safety of 9-NC in MDS and CMML.
  
  
  METHODS
  Adults with a diagnosis of MDS (n = 12) and CMML (n = 32) received 9-NC 2 mg/m(2) orally daily 5 days a week, every 4 to 6 weeks.
  
  
  RESULTS
  Overall, 5 (11%) patients achieved complete response (CR), 7 (16%) had a partial response (PR), and 6 (14%) had hematologic improvement (HI), for an overall response rate of 41%. The response rate was similar in MDS and CMML. Severe (Grade 3-4) side effects included nausea and vomiting (7%), diarrhea (18%), other gastrointestinal toxicities (5%), and genitourinary toxicities (12%).
  
  
  CONCLUSIONS
  9-NC is active in MDS and CMML. The paucity of available therapies in CMML makes 9-NC a good candidate for further studies as a single agent, or in combination with decitabine, 5-azacitidine or cytarabine.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintas-Cardama
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Jenny
authors.initials: J
authors.lastname: Shan
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C079905:rubitecan; D002166:Camptothecin