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Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies†
Article first published online: 12 MAY 2008
Published 2008 American Cancer Society
Volume 113, Issue 2, pages 360–366, 15 July 2008
How to Cite
Borthakur, G., Alvarado, Y., Ravandi-Kashani, F., Cortes, J., Estrov, Z., Faderl, S., Ivy, P., Bueso-Ramos, C., Nebiyou Bekele, B. and Giles, F. (2008), Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies. Cancer, 113: 360–366. doi: 10.1002/cncr.23559
This article is a US government work and, as such, is in the public domain in the United States of America.
- Issue published online: 8 JUL 2008
- Article first published online: 12 MAY 2008
- Manuscript Accepted: 10 MAR 2008
- Manuscript Revised: 4 MAR 2008
- Manuscript Received: 27 NOV 2007
- rebeccamycin analog;
- phase 1
XL119 is a water-soluble derivative of rebeccamycin with dose-dependent myelosuppression as dose-limiting toxicity in phase 1 studies of solid tumors. A phase 1 study was conducted to determine the maximum tolerated dose and toxicities of XL119 in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias.
Thirty-one patients were treated at 7 dose levels ranging from 140 to 260 mg/m2/daily times 5 in a 21-day cycle. Consenting patients had correlative biologic parameters studied.
Dose-limiting toxicity was grade 3/4 mucositis. The recommended phase 2 dose in hematologic malignancies is 240 mg/m2/daily times 5 in a 21-day cycle. Clinically significant reduction in bone marrow blasts were seen in 5 patients and additional patients had reductions in peripheral blood blasts. However, the responses were transient. Changes of plasma vascular endothelial growth factor levels from Day 1 to Day 7 correlated negatively with changes in peripheral blood blasts from Day 1 to Day 7.
Further assessment of XL119 in combination with other agents in patients with acute leukemias and high-risk myelodysplastic syndrome is warranted. Cancer 2008. Published 2008 by the American Cancer Society.