title: Liposomal vincristine in relapsed non-Hodgkin's lymphomas: early results of an ongoing phase II trial.
abstract: OBJECTIVE
  Vincristine is an active agent in lymphomas, but is often neurotoxic, and the resulting dose reductions have been associated with lower remission and survival rates in Hodgkin's disease. Liposomal vincristine (Onco-TCS) has prolonged half-life, reaches higher concentration in tumors and lymph nodes than in nerves, and administered at full doses appears to be less neurotoxic, and more active then free vincristine in mice bearing L-1210 and P-388 leukemias. We therefore explored its activity in relapsed non-Hodgkin's lymphomas (NHL) and acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Eligible patients had histologically proven relapse, age > or = 16 years, normal renal function, neutrophils > 500/microliter, platelets > 50,000/microliter, and no HIV infection, central nervous system disease, or serious neuropathy. Patients were treated with 2.0 mg/m2 of liposomal vincristine i.v. over 60 minutes q 14 days. Responders received up to 12 injections.
  
  
  RESULTS
  Of the 51 registered patients, 35 are currently evaluable for response. Median age was 62 years (range 19-86), and 21 were male. The median number of prior regimens was 3 (range 1-10) and had included vincristine in all patients, of whom 51% were refractory to their last regimen. Serum LDH was high in 46%, and beta 2-microglobulin > 3.0 mg/l in 63% of patients. Of the 155 administered injections, 138 (89%) were at the 2.0 mg/m2 level. The median injected dose was 3.8 mg (range 2.6-4.8 mg), and median number of injections was 4 (range 1-12). Responses were seen in 14 of 34 (41%) patients with NHL (95% confidence intervals (95% CI) 25%-59%). Response rates were 10% for indolent, 71% for transformed, and 47% for aggressive NHL, but the 95% confidence intervals overlapped. Median progression-free survival was 5.5 months for responders. Grade 3-4 motor or sensory neuropathy was seen in 11, and caused termination of therapy in five patients. All five had prior neuropathy, two had previously received paclitaxel, one platinum, and two paclitaxel and platinum. Fever was detected in three patients, but there were no toxic deaths.
  
  
  CONCLUSIONS
  Liposomal vincristine is active and well tolerated in this heavily pretreated population with relapsed NHL, but can be neurotoxic in a fraction of patients heavily exposed to prior neurotoxic agents. These data, if confirmed, would suggest a potential role for liposomal vincristine in the combination therapy of previously untreated patients with NHL.
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, USA. asarris@notes.mdacc.tmc.edu
authors.forename: A H
authors.initials: AH
authors.lastname: Sarris
authors.forename: F
authors.initials: F
authors.lastname: Hagemeister
authors.forename: J
authors.initials: J
authors.lastname: Romaguera
authors.forename: M A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: P
authors.initials: P
authors.lastname: McLaughlin
authors.forename: A M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: L J
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: B
authors.initials: B
authors.lastname: Samuels
authors.forename: O
authors.initials: O
authors.lastname: Pate
authors.forename: M
authors.initials: M
authors.lastname: Oholendt
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: C
authors.initials: C
authors.lastname: Burge
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012008:Recurrence; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D014750:Vincristine