title: Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies.
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.
authors.affiliation: Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA. gborthak@mdanderson.org
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Yesid
authors.initials: Y
authors.lastname: Alvarado
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi-Kashani
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: B
authors.initials: B
authors.lastname: Nebiyou Bekele
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000150:complications; D001706:Biopsy; D001853:Bone Marrow / Q000187:drug effects; D002227:Carbazoles / Q000009:adverse effects / Q000737:chemistry* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D014777:Virus Diseases / Q000150:complications
chemical_list: D002227:Carbazoles; D005960:Glucosides; C053339:rebeccamycin; C093269:becatecarin