| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Trials |
1 Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, and 2 Vion Pharmaceuticals, Inc., New Haven, Connecticut
ABSTRACT
Purpose: VNP40101M is a novel sulfonylhydrazine alkylating agent with broad antitumor activity in animal models. As alkylating agents are important antileukemia drugs, a Phase I and pharmacokinetic study of VNP40101M was conducted in patients with refractory or relapsed leukemias or poor-risk myelodysplastic syndromes (MDS).
Experimental Design: VNP40101M was given as a single i.v. infusion over 15–70 min on day 1. Courses were repeated every 4 weeks according to antileukemic activity. The starting dose of 220 mg/m2 was escalated by 
33% in cohorts of 3–6 patients until a maximum-tolerated dose was established. One additional cohort was treated with the maximum-tolerated dose divided over days 1 and 8.
Results: Thirty-eight patients, including 28 with acute myeloid leukemia and 5 with MDS, received 52 courses of treatment. Nondose-limiting, reversible infusion-related toxicities were the most frequent adverse event, occurring in 24 (63%) patients on the first course. Dose escalation was terminated at 708 mg/m2 for prolonged myelosuppression in 1 of 7 patients, and 600 mg/m2 was selected as the recommended Phase II dose, with no significant extramedullary toxicity at this dose level. Two patients, 1 with MDS treated with 300 mg/m2 and 1 with acute myeloid leukemia treated with 600 mg/m2, achieved complete remission.
Conclusions: VNP40101M had significant antileukemic activity and minimal extramedullary toxicity in patients with relapsed or refractory disease.
This article has been cited by other articles:
|
|
 |
|
  S. Gururangan, C. D. Turner, C. F. Stewart, M. O'Shaughnessy, M. Kocak, T. Y. Poussaint, P. C. Phillips, S. Goldman, R. Packer, I. F. Pollack, et al. Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study Clin. Cancer Res., February 15, 2008; 14(4): 1124 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Stone Genetically Defined Prognostic Factors and Novel Therapeutics for AML ASCO Educational Book, January 1, 2008; 2008(1): 280 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Badruddoja, S. T. Keir, I. King, J. Zeidner, J. J. Vredenburgh, L. H. Muhlbaier, D. D. Bigner, and H. S. Friedman Activity of VNP40101M (Cloretazine) in the treatment of CNS tumor xenografts in athymic mice Neuro-oncol, July 1, 2007; 9(3): 240 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Giles, D. Rizzieri, J. Karp, N. Vey, F. Ravandi, S. Faderl, K. Dad Khan, G. Verhoef, P. Wijermans, A. Advani, et al. Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, in Patients Age 60 Years or Older With Previously Untreated Acute Myeloid Leukemia J. Clin. Oncol., January 1, 2007; 25(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ishiguro, H. A. Seow, P. G. Penketh, K. Shyam, and A. C. Sartorelli Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine. Mol. Cancer Ther., April 1, 2006; 5(4): 969 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishiguro, K. Shyam, P. G. Penketh, and A. C. Sartorelli Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine Mol. Cancer Ther., November 1, 2005; 4(11): 1755 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Giles, S. Verstovsek, D. Thomas, S. Gerson, J. Cortes, S. Faderl, A. Ferrajoli, F. Ravandi, S. Kornblau, G. Garcia-Manero, et al. Phase I Study of Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, Combined with Cytarabine in Patients with Refractory Leukemia Clin. Cancer Res., November 1, 2005; 11(21): 7817 - 7824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Seow, P. G. Penketh, K. Shyam, S. Rockwell, and A. C. Sartorelli PNAS, June 28, 2005; 102(26): 9282 - 9287. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
