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Title: KRN8602 (MX2-hydrochloride): an active new agent for the treatment of recurrent high-grade glioma.
Austin Authors: Clarke, K;Basser, R L;Underhill, C;Mitchell, Paul L R ;Bartlett, John;Cher, Lawrence M ;Findlay, M;Dalley, D;Pell, M;Byrne, M;Geldard, H;Hill, J S;Maher, D;Fox, R M;Green, M D;Kaye, A H
Affiliation: Centre for Developmental Cancer Therapeutics, Parkville, Victoria (affiliates: Ludwig Institute Oncology Unit, Austin & Repatriation Medical Centre, Australia
Issue Date: 1-Aug-1999
Publication information: Journal of Clinical Oncology; 17(8): 2579-84
Abstract: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma.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 < or = 2) were treated with an intravenous bolus of 40 mg/m(2) 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.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.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.
Gov't Doc #: 10561325
Type: Journal Article
Subjects: Adolescent
Antibiotics, Antineoplastic.adverse effects.therapeutic use
Astrocytoma.drug therapy.mortality
Brain Neoplasms.drug therapy.mortality.pathology
Carubicin.adverse effects.analogs & derivatives.therapeutic use
Combined Modality Therapy
Glioblastoma.drug therapy.mortality
Middle Aged
Neoplasm Recurrence, Local.drug therapy
Neutropenia.chemically induced
Survival Analysis
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