title: Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non-Hodgkin lymphoma: report of the pivotal phase 2 study.
abstract: BACKGROUND
  Marqibo, a sphingosomal/cholesterol encapsulation of vincristine sulfate has targeted, increased, and sustained delivery of vincristine to tumor tissues. A phase 2, open-label, single-arm, and multinational study evaluated the efficacy and tolerability of Marqibo as a single agent in patients with multiply relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).
  
  
  METHODS
  Eligible patients had relapsed or refractory de novo or transformed aggressive NHL and prior treatment with at least 2 multiagent chemotherapy regimens. Marqibo was administered at 2 mg/m2, every 2 weeks, for a maximum of 12 cycles or until toxicity or disease progression.
  
  
  RESULTS
  One hundred and nineteen patients were enrolled and treated on trial. Ninety-six had histological confirmed de novo (N=89) or transformed (N=7) aggressive NHL. Median number of cycles was 4 (median dose/cycle 4 mg). Overall response (CR and complete response unconfirmed and PR) was 25% (95% confidence interval [CI], 17, 35), CR and complete response unconfirmed confirmed by external reviewers was 5%. Median overall survival was 6.6 months (Kaplan-Meier estimate, 95% CI, 4.7, 9.8). Grade 3 of 4 neurotoxicity occurred in 32% of patients. All patients had prior neurotoxic agents, and 85% had baseline residual neuropathy symptoms (grades 1-2) from prior treatment.
  
  
  CONCLUSIONS
  Marqibo is an active agent in patients with heavily pretreated aggressive NHL, and tolerated at approximately twice the dose intensity of standard vincristine. Its activity supports further investigation as a substitution for vincristine in combination treatment of lymphoid disorders.
authors.affiliation: Lymphoma/Myeloma Department, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. marodriguez@mdanderson.org
authors.forename: M A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Robert
authors.initials: R
authors.lastname: Pytlik
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Randy
authors.initials: R
authors.lastname: Gascoyne
authors.forename: Biao
authors.initials: B
authors.lastname: Lu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Deitcher
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014750:Vincristine