This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clarke, K. Articles by Kaye, A. H. Search for Related Content PubMed PubMed Citation Articles by Clarke, K. Articles by Kaye, A. H. Social Bookmarking                            What's this?

KRN8602 (MX2-Hydrochloride): An Active New Agent for the Treatment of Recurrent High-Grade Glioma

From the Centre for Developmental Cancer Therapeutics, Parkville, Victoria (affiliates: Ludwig Institute Oncology Unit, Austin & Repatriation Medical Centre; Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research; Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital; and Department of Neurosurgery, University of Melbourne, Melbourne); Department of Medical Oncology, Sydney Cancer Centre, Sydney; St Vincent's Hospital, Darlinghurst; Department of Medical Oncology, Sir Charles Gardiner Hospital, Nedlands; and Institute of Drug Technology/Biomedicus, Victoria, Australia.

Address reprint requests to R. Basser, MBBS, Centre for Developmental Cancer Therapeutics, c/o Post Office, Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia; email basser{at}licre.ludwig.edu.au

PURPOSE: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma.

PATIENTS AND METHODS: Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score 2) were treated with an intravenous bolus of 40 mg/m² KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles.

RESULTS: A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting.

CONCLUSION: KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. Minotti, P. Menna, E. Salvatorelli, G. Cairo, and L. Gianni Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity Pharmacol. Rev., June 1, 2004; 56(2): 185 - 229. [Abstract] [Full Text] [PDF]

				S. L. Chua, M. A. Rosenthal, S. S. Wong, D. M. Ashley, A.-m. Woods, A. Dowling, and L. M. Cher Phase 2 study of temozolomide and Caelyx in patients with recurrent glioblastoma multiforme Neuro-oncol, January 1, 2004; 6(1): 38 - 43. [Abstract] [PDF]