title: High-dose vincristine sulfate liposome injection (Marqibo) Is not associated with clinically meaningful hematologic toxicity.
abstract: BACKGROUND
  Vincristine sulfate liposome injection (VSLI) facilitates vincristine dose intensification and densification, is active in untreated and relapsed lymphoma, and has been approved in the United States for relapsed and refractory acute lymphoblastic leukemia. Cancer- and concomitant chemotherapy-related anemia, neutropenia, and thrombocytopenia in patients with hematologic malignancy have complicated the evaluation of hematologic toxicity related to new drugs.
  
  
  METHODS
  We assessed the hematologic toxicity of VSLI 2.25 mg/m(2) administered every 14 (cohort 1) or 7 (cohort 2) days in 54 patients with metastatic uveal melanoma, a cancer not known to involve the bone marrow.
  
  
  RESULTS
  Cohort 2 received a greater median number of VSLI doses (6 vs. 4) within a shorter median period (5.7 vs. 8.7 weeks), resulting in a larger median cumulative exposure (22.6 vs. 17.7 mg) and near doubling of the median dose density (2.2 vs. 4.0 mg/wk) compared with cohort 1. Despite greater VSLI exposure and dose density, cohort 2 had a lower median decrease from baseline in the neutrophil count and a greater increase from baseline in the platelet count compared with cohort 1. Hematologic adverse events (AEs) were uncommon and mostly grade 1 or 2 in severity. No grade 4 hematologic AEs developed.
  
  
  CONCLUSIONS
  VSLI at its approved dose resulted in a low incidence of clinically meaningful hematologic toxicity. A near doubling of the median dose density did not have an identifiable effect on the reported incidence and severity of hematologic AEs. VSLI could be well suited for use combined with myelosuppresive drugs and for patients unable to tolerate peripheral blood cytopenia.
authors.affiliation: Talon Therapeutics, Inc, South San Francisco, CA.
authors.forename: Olivia R
authors.initials: OR
authors.lastname: Deitcher
authors.affiliation: University of California, Los Angeles, CA.
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.affiliation: University of Colorado Denver, Aurora, CO.
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Thomas Jefferson University, Philadelphia, PA.
authors.forename: Takami
authors.initials: T
authors.lastname: Sato
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.affiliation: Talon Therapeutics, Inc, South San Francisco, CA.
authors.forename: Karen
authors.initials: K
authors.lastname: Segarini
authors.affiliation: Talon Therapeutics, Inc, South San Francisco, CA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Silverman
authors.affiliation: Talon Therapeutics, Inc, South San Francisco, CA. Electronic address: srdeitcher@hotmail.com.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Deitcher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001772:Blood Cell Count; D004909:Erythrocyte Indices / Q000187:drug effects*; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects*; D000098943:Uveal Melanoma
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014750:Vincristine
keywords: Anemia; Liposome; Neutropenia; Thrombocytopenia; Vincristine