Work

Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies

Year: 2008

Type: article

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/m(2)/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.

Source: Cancer

DOI: 10.1002/cncr.23559