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 A.; Karp, Judith E.; Vey, Norbert; Ravandi, Farhad; Faderl, Stefan; Khan, Khuda Dad; Verhoef, Gregor; Wijermans, Pierre W.; Advani, Anjali S.; Roboz, Gail J.; Kantarjian, Hagop M.; Bilgrami, Syed; Ferrant, Augustin; Daenen, Simon; Karsten, Verena; Cahill, Ann; Albitar, Mäher; Mufti, Ghulam J.; O’Brien, Susan

doi:10.1200/jco.2006.07.0961

Cited by 82 publications

(54 citation statements)

References 37 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although low-TRM rates (10-15%) were observed in the previous clinical trials for elderly AML patients, the CR rates in those studies were less than 50% [34][35][36]. In recent promising studies showing a CR rate >50% in elderly AML patients, the TRM rate was 25% [37].…”

Section: Discussionmentioning

confidence: 93%

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

et al. 2012

View full text Add to dashboard Cite

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m 2 , days 1-4), cytarabine (1,000 mg/m 2 , days 1-4), and attenuated-dose idarubicin (5 mg/ m 2 , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F 5 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Am. J. Hematol. 88:10-15, 2013. V

show abstract

Section: Discussionmentioning

confidence: 93%

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

et al. 2012

View full text Add to dashboard Cite

show abstract

“…While the lack of statistical results is clearly related to the low number of patients in the group with poor cytogenetcis, our data do strongly suggest the opportunity of allocating older AML patients with unfavourable karyotype into experimental trials, based on new agents, such as clofarabine or cloretazine, potentially able to overcome the adverse prognostic relevance of adverse karyotypic alterations [41][42][43][44]. These agents could also be taken into account to design new and more active conditioning regimens to ASCT.…”

Section: Discussionmentioning

confidence: 96%

Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan

Ferrara

Palmieri

Pedata

et al. 2009

Hematological Oncology

View full text Add to dashboard Cite

Different studies have suggested the potential utility of autologous stem cell transplantation (ASCT) in acute myeloid leukaemia (AML) of the elderly with encouraging results in selected patients. However, while the introduction of peripheral blood stem cells (PBSC) has consistently reduced morbidity and mortality of the procedure, relapse still represents the major cause of ASCT failure. One possibility to ameliorate therapeutic results could rely on the adoption of conditioning regimens specifically designed for AML. We report therapeutic results from a series of 40 AML patients older than 60 years (median age 67 years) autografted in first complete remission (CR), after conditioning with continuous infusion (c.i.) high dose idarubicin and busulphan. Fourty patients (median age: 67 years) received 2 days c.i. idarubicin at 20 mg/m 2 /day, followed by 3 days oral or intravenous busulphan (4 mg/kg/day) as conditioning. No case of transplant-related mortality occurred. Cardiac toxicity was absent, while 31 patients (77%) had grade 3-4 mucositis. After a median follow-up of 25 months, median disease free and overall survival (OS) for the whole patient population were 13 and 22 months, respectively. Three patients died while in CR from causes unrelated to AML. Better results were achieved in patients with intermediate karyotype as opposed to those with adverse cytogenetics. Our data confirm the feasibility of a conditioning regimen based on high-dose idarubicin plus busulphan in older selected AML patients and suggest clinical improvement in patients with normal cytogenetics.

show abstract

“…Some hope is being raised by new options, such as hypomethylating agents, clofarabine, or cloretazine, which have recently been associated with relatively good response rates in older patients with cytogenetically unfavorable AML or high-risk MDS. [24][25][26][27][28] Unfortunately, cases of good-risk cytogenetics are rare among older AML patients. In this ALFA-9803 study, only 12 patients (3%) had either t(8;21) or inv (16) and, even though their estimated 2-year overall survival was 46% compared to the 31% in patients with a normal karyotype, the difference was not statistically significant (p=0.20).…”

Section: Discussionmentioning

confidence: 99%

Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia

Etienne²,

et al. 2008

View full text Add to dashboard Cite

show abstract

Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, in Patients Age 60 Years or Older With Previously Untreated Acute Myeloid Leukemia

Abstract: 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.

Cited by 82 publications

References 37 publications

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan

Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia

Contact Info

Product

Resources

About