A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome

Stefan Faderl, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Zeev Estrov, Varsha Gandhi, Anna L. Byrd, Monica Kwari, Jorge Cortes, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m 2 vs 30 mg/m 2 daily à - 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m 2 and 29% at 30 mg/m 2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m 2 of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.

Original languageEnglish (US)
Pages (from-to)722-728
Number of pages7
JournalCancer
Volume118
Issue number3
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Methyltransferases
Therapeutics
Poisons
DNA
clofarabine
Nucleosides
Appointments and Schedules
Kidney
Safety
Survival
Mortality
Liver
Neoplasms

Keywords

  • clofarabine
  • DNA methyltransferase inhibitors
  • myelodysplastic syndrome
  • nucleoside analogs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Faderl, S., Garcia-Manero, G., Jabbour, E., Ravandi, F., Borthakur, G., Estrov, Z., ... Kantarjian, H. M. (2012). A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome. Cancer, 118(3), 722-728. https://doi.org/10.1002/cncr.26327

A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome. / Faderl, Stefan; Garcia-Manero, Guillermo; Jabbour, Elias; Ravandi, Farhad; Borthakur, Gautam; Estrov, Zeev; Gandhi, Varsha; Byrd, Anna L.; Kwari, Monica; Cortes, Jorge; Kantarjian, Hagop M.

In: Cancer, Vol. 118, No. 3, 01.02.2012, p. 722-728.

Research output: Contribution to journalArticle

Faderl, S, Garcia-Manero, G, Jabbour, E, Ravandi, F, Borthakur, G, Estrov, Z, Gandhi, V, Byrd, AL, Kwari, M, Cortes, J & Kantarjian, HM 2012, 'A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome', Cancer, vol. 118, no. 3, pp. 722-728. https://doi.org/10.1002/cncr.26327
Faderl, Stefan ; Garcia-Manero, Guillermo ; Jabbour, Elias ; Ravandi, Farhad ; Borthakur, Gautam ; Estrov, Zeev ; Gandhi, Varsha ; Byrd, Anna L. ; Kwari, Monica ; Cortes, Jorge ; Kantarjian, Hagop M. / A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome. In: Cancer. 2012 ; Vol. 118, No. 3. pp. 722-728.
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T1 - A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome

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AU - Ravandi, Farhad

AU - Borthakur, Gautam

AU - Estrov, Zeev

AU - Gandhi, Varsha

AU - Byrd, Anna L.

AU - Kwari, Monica

AU - Cortes, Jorge

AU - Kantarjian, Hagop M.

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N2 - BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m 2 vs 30 mg/m 2 daily à - 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m 2 and 29% at 30 mg/m 2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m 2 of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.

AB - BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m 2 vs 30 mg/m 2 daily à - 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m 2 and 29% at 30 mg/m 2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m 2 of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.

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