title: Combined modality radioimmunotherapy with Taxol and 90Y-Lym-1 for Raji lymphoma xenografts.
abstract: Despite effective therapies for non-Hodgkin's lymphoma (NHL), the majority of patients are not cured. Radioimmunotherapy (RIT) has shown good results in preclinical and clinical trials even in patients that are non-responsive to standard chemotherapy. To make RIT more effective, agents such as paclitaxel (Taxol), that can enhance radiation effects, are being tested. Nude mice bearing human Burkitt's lymphoma (Raji) xenografts were treated with: 1) 150 or 200 microCi (5.5 or 7.3 MBq) of 90Y-2IT-BAD-Lym-1 alone, 2) 600 micrograms of Taxol alone, 3) 150 or 200 microCi of 90Y-2IT-BAD-Lym-1 plus 600 micrograms of Taxol given 24 hours after RIT, or 4) no treatment. Tumor size, survival, mouse weight and blood counts were monitored to assess efficacy and toxicity. Survival for mice treated in this 84 day trial was: 71% for 90Y-2IT-BAD-Lym-1 (200 microCi) plus Taxol, 29% for Taxol alone, 6% for 90Y-2IT-BAD-Lym-1 (200 microCi) alone and 14% in the untreated group. Average tumor volume in the 90Y-2IT-BAD-Lym-1 (200 microCi) plus Taxol group was reduced by 89 and 99% compared to the RIT alone and Taxol alone groups, respectively. Mice treated with 150 microCi had less toxicity than those treated with 200 microCi of 90Y-2IT-BAD-Lym-1, however, the higher radiation dose, and Taxol, were required for improved survival. Mouse weights and myelotoxicity in the combined modality (RIT plus Taxol) groups were similar to those receiving the same dose of RIT alone. In the Raji tumored nude mouse model, addition of Taxol to 90Y-2IT-BAD-Lym-1, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity.
authors.affiliation: Department of Internal Medicine, University of California, Davis, Medical Center, Sacramento 95816, USA. rtodonnell@ucdavis.edu
authors.forename: R T
authors.initials: RT
authors.lastname: O'Donnell
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: L A
authors.initials: LA
authors.lastname: Miers
authors.forename: D L
authors.initials: DL
authors.lastname: Kukis
authors.forename: G R
authors.initials: GR
authors.lastname: Mirick
authors.forename: L A
authors.initials: LA
authors.lastname: Kroger
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C410508:2IT-BAD-Lym-1 monoclonal antibody; D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D017239:Paclitaxel