Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia

Cancer. 2006 Oct 1;107(7):1525-9. doi: 10.1002/cncr.22186.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Female
  • Humans
  • Leukemia, Myelomonocytic, Chronic / drug therapy*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Topoisomerase I Inhibitors*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • rubitecan
  • Camptothecin