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Activity of 9‐nitro‐camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia
Author(s) -
QuintasCardama Alfonso,
Kantarjian Hagop,
O'Brien Susan,
Jabbour Elias,
Giles Francis,
Ravandi Farhad,
Faderl Stefan,
Pierce Sherry,
Shan Jenny,
Verstovsek Srdan,
Cortes Jorge
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22186
Subject(s) - medicine , chronic myelomonocytic leukemia , nausea , topotecan , decitabine , azacitidine , gastroenterology , camptothecin , myelodysplastic syndromes , neutropenia , oncology , leukemia , pharmacology , chemotherapy , bone marrow , dna methylation , biochemistry , gene expression , chemistry , organic chemistry , gene
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. Cancer 2006. © 2006 American Cancer Society.