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.
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.
Authors: A Dowlati; C L Hoppel; S T Ingalls; S Majka; X Li; N Sedransk; T Spiro; S L Gerson; P Ivy; S C Remick Journal: J Clin Oncol Date: 2001-04-15 Impact factor: 44.544
Authors: P Korkolopoulou; E Apostolidou; P M Pavlopoulos; N Kavantzas; N Vyniou; I Thymara; E Terpos; E Patsouris; X Yataganas; P Davaris Journal: Leukemia Date: 2001-09 Impact factor: 11.528
Authors: Bruce D Cheson; Peter L Greenberg; John M Bennett; Bob Lowenberg; Pierre W Wijermans; Stephen D Nimer; Antonio Pinto; Miloslav Beran; Theo M de Witte; Richard M Stone; Moshe Mittelman; Guillermo F Sanz; Steven D Gore; Charles A Schiffer; Hagop Kantarjian Journal: Blood Date: 2006-04-11 Impact factor: 22.113
Authors: Jorge Cortes; Hagop Kantarjian; Maher Albitar; Deborah Thomas; Stefan Faderl; Charles Koller; Guillermo Garcia-Manero; Francis Giles; Michael Andreeff; Susan O'Brien; Michael Keating; Elihu Estey Journal: Cancer Date: 2003-03-01 Impact factor: 6.860
Authors: Joseph Merchant; Kendra Tutsch; Amy Dresen; Rhoda Arzoomanian; Dona Alberti; Chris Feierabend; Kim Binger; Rebecca Marnoccha; James Thomas; Jim Cleary; George Wilding Journal: Clin Cancer Res Date: 2002-07 Impact factor: 12.531