Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia.
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.
Quintas-Cardama
Alfonso
A
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Kantarjian
Hagop
H
O'Brien
Susan
S
Jabbour
Elias
E
Giles
Francis
F
Ravandi
Farhad
F
Faderl
Stefan
S
Pierce
Sherry
S
Shan
Jenny
J
Verstovsek
Srdan
S
Cortes
Jorge
J
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
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C079905:rubitecan; D002166:Camptothecin