Abstract
BACKGROUND. 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. METHODS. 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. RESULTS. Dose-limiting toxicity was grade 3/4 mucositis. The recommended phase 2 dose in hematologic malignancies is 240 mg/m 2/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. CONCLUSIONS. Further assessment of XL119 in combination with other agents in patients with acute leukemias and high-risk myelodysplastic syndrome is warranted.
Original language | English (US) |
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Pages (from-to) | 360-366 |
Number of pages | 7 |
Journal | Cancer |
Volume | 113 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2008 |
Externally published | Yes |
Keywords
- Leukemia
- Phase 1
- Rebeccamycin analog
- XL119
ASJC Scopus subject areas
- Oncology
- Cancer Research