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

Alfonso Quintas-Cardama, Hagop Kantarjian, Susan O'Brien, Elias Jabbour, Francis Giles, Farhad Ravandi, Stefan Faderl, Sherry Pierce, Jenny Shan, Srdan Verstovsek, Jorge Cortes

Research output: Contribution to journalArticle

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/m2 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 toricities (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.

Original languageEnglish (US)
Pages (from-to)1525-1529
Number of pages5
JournalCancer
Volume107
Issue number7
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

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Leukemia, Myelomonocytic, Chronic
Topoisomerase I Inhibitors
Camptothecin
Myelodysplastic Syndromes
decitabine
Topoisomerase Inhibitors
Topotecan
Safety
Azacitidine
Cytarabine
Nausea
Vomiting
Diarrhea

Keywords

  • 9-nitrocamptothecin
  • Chronic myelomonocytic leukemia
  • Myelodysplastic syndrome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia. / Quintas-Cardama, Alfonso; Kantarjian, Hagop; O'Brien, Susan; Jabbour, Elias; Giles, Francis; Ravandi, Farhad; Faderl, Stefan; Pierce, Sherry; Shan, Jenny; Verstovsek, Srdan; Cortes, Jorge.

In: Cancer, Vol. 107, No. 7, 01.10.2006, p. 1525-1529.

Research output: Contribution to journalArticle

Quintas-Cardama, A, Kantarjian, H, O'Brien, S, Jabbour, E, Giles, F, Ravandi, F, Faderl, S, Pierce, S, Shan, J, Verstovsek, S & Cortes, J 2006, 'Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia', Cancer, vol. 107, no. 7, pp. 1525-1529. https://doi.org/10.1002/cncr.22186
Quintas-Cardama, Alfonso ; Kantarjian, Hagop ; O'Brien, Susan ; Jabbour, Elias ; Giles, Francis ; Ravandi, Farhad ; Faderl, Stefan ; Pierce, Sherry ; Shan, Jenny ; Verstovsek, Srdan ; Cortes, Jorge. / Activity of 9-nitro-camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia. In: Cancer. 2006 ; Vol. 107, No. 7. pp. 1525-1529.
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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/m2 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 toricities (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.",
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AU - Quintas-Cardama, Alfonso

AU - Kantarjian, Hagop

AU - O'Brien, Susan

AU - Jabbour, Elias

AU - Giles, Francis

AU - Ravandi, Farhad

AU - Faderl, Stefan

AU - Pierce, Sherry

AU - Shan, Jenny

AU - Verstovsek, Srdan

AU - Cortes, Jorge

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N2 - 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/m2 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 toricities (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.

AB - 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/m2 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 toricities (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.

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