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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


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
Issue number1
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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