Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia

Francis J. Giles, David Rizzieri, Judith Karp, Norbert Vey, Farhad Ravandi, Stefan Faderl, Khuda Dad Khan, Gregor Verhoef, Pierre Wijermans, Anjali Advani, Gail Roboz, Hagop Kantarjian, Syed Fazl Ali Bilgrami, Augustin Ferrant, Simon M G J Daenen, Verena Karsten, Ann Cahill, Maher Albitar, Ghulam Mufti, Susan O'Brien

Research output: Contribution to journalArticle

Abstract

Purpose: Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Patients and Methods: Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity. Results: One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR. Conclusion: Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Alkylating Agents
Acute Myeloid Leukemia
Cytogenetics
Myelodysplastic Syndromes
laromustine
Comorbidity
Survival
Cell Transplantation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. / Giles, Francis J.; Rizzieri, David; Karp, Judith; Vey, Norbert; Ravandi, Farhad; Faderl, Stefan; Khan, Khuda Dad; Verhoef, Gregor; Wijermans, Pierre; Advani, Anjali; Roboz, Gail; Kantarjian, Hagop; Bilgrami, Syed Fazl Ali; Ferrant, Augustin; Daenen, Simon M G J; Karsten, Verena; Cahill, Ann; Albitar, Maher; Mufti, Ghulam; O'Brien, Susan.

In: Journal of Clinical Oncology, Vol. 25, No. 1, 01.01.2007, p. 25-31.

Research output: Contribution to journalArticle

Giles, FJ, Rizzieri, D, Karp, J, Vey, N, Ravandi, F, Faderl, S, Khan, KD, Verhoef, G, Wijermans, P, Advani, A, Roboz, G, Kantarjian, H, Bilgrami, SFA, Ferrant, A, Daenen, SMGJ, Karsten, V, Cahill, A, Albitar, M, Mufti, G & O'Brien, S 2007, 'Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia', Journal of Clinical Oncology, vol. 25, no. 1, pp. 25-31. https://doi.org/10.1200/JCO.2006.07.0961
Giles, Francis J. ; Rizzieri, David ; Karp, Judith ; Vey, Norbert ; Ravandi, Farhad ; Faderl, Stefan ; Khan, Khuda Dad ; Verhoef, Gregor ; Wijermans, Pierre ; Advani, Anjali ; Roboz, Gail ; Kantarjian, Hagop ; Bilgrami, Syed Fazl Ali ; Ferrant, Augustin ; Daenen, Simon M G J ; Karsten, Verena ; Cahill, Ann ; Albitar, Maher ; Mufti, Ghulam ; O'Brien, Susan. / Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 1. pp. 25-31.
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abstract = "Purpose: Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Patients and Methods: Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity. Results: One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30{\%}) and no patient had a favorable karyotype. Forty-seven patients (45{\%}) had cardiac disease, 25 patients (24{\%}) had hepatic disease, and 19 patients (18{\%}) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32{\%}, with 29 patients (28{\%}) achieving complete response (CR) and four patients (4{\%}) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50{\%}, 11{\%}, and 40{\%}, respectively. Response by cytogenetic risk category was 39{\%} in 56 patients with intermediate cytogenetic risk and 24{\%} in 46 patients with unfavorable cytogenetic risk. Nineteen (18{\%}) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14{\%}; the median duration of survival was 147 days, with a 1-year survival of 28{\%} for those who achieved CR. Conclusion: Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.",
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T1 - Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia

AU - Giles, Francis J.

AU - Rizzieri, David

AU - Karp, Judith

AU - Vey, Norbert

AU - Ravandi, Farhad

AU - Faderl, Stefan

AU - Khan, Khuda Dad

AU - Verhoef, Gregor

AU - Wijermans, Pierre

AU - Advani, Anjali

AU - Roboz, Gail

AU - Kantarjian, Hagop

AU - Bilgrami, Syed Fazl Ali

AU - Ferrant, Augustin

AU - Daenen, Simon M G J

AU - Karsten, Verena

AU - Cahill, Ann

AU - Albitar, Maher

AU - Mufti, Ghulam

AU - O'Brien, Susan

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Purpose: Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Patients and Methods: Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity. Results: One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR. Conclusion: Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.

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