title: The radioisotope contributes significantly to the activity of radioimmunotherapy.
abstract: OBJECTIVE
  A multicenter, randomized study was undertaken to estimate the single agent activity of Tositumomab and to determine the contribution of radioisotope-labeling with (131)I to activity and toxicity by comparing treatment outcomes for Tositumomab and Iodine I 131 Tositumomab (BEXXAR) to an equivalent total dose of unlabeled Tositumomab.
  
  
  METHODS
  Seventy-eight patients with refractory/relapsed non-Hodgkin's lymphoma were randomized to either unlabeled Tositumomab or Iodine I 131 Tositumomab. Patients progressing after unlabeled Tositumomab could cross over to receive Iodine I 131 Tositumomab. The median follow-up at analysis was 42.6 months (range 1.9 to 71.5 months).
  
  
  RESULTS
  Responses in the Iodine I 131 Tositumomab versus unlabeled Tositumomab groups: overall response 55% versus 19% (P = 0.002); complete response 33% versus 8% (P = 0.012); median duration of overall response not reached versus 28.1 months (95% confidence interval: 7.6, not reached); median duration of complete response not reached in either arm; and median TTP 6.3 versus 5.5 months (P = 0.031), respectively. Of the patients who had a complete response after initial Iodine I 131 Tositumomab therapy, 71% (10 of 14) continued in complete response at 29.8 to 71.1 months. Two patients who achieved a complete response after unlabeled Tositumomab had ongoing responses at 48.1 to 56.9 months. Nineteen patients received Iodine I 131 Tositumomab crossover therapy. Responses after crossover versus prior response to unlabeled Tositumomab were as follows: complete response rates of 42% versus 0% (P = 0.008); overall response 68% versus 16% (P = 0.002); median durations of overall response 12.6 versus 7.6 months (P = 0.001); and median TTP 12.4 versus 5.5 months (P = 0.01), respectively. Hematologic toxicity was more severe and nonhematologic adverse events were more frequent after Iodine I 131 Tositumomab than after Tositumomab alone. Elevated thyrotropin occurred in 5% of patients. Seroconversion to human antimurine antibody after Iodine I 131 Tositumomab, unlabeled Tositumomab, and Iodine I 131 Tositumomab-crossover was 27%, 19%, and 0%, respectively.
  
  
  CONCLUSIONS
  Unlabeled Tositumomab showed single agent activity, but in this direct comparison, all of the therapeutic outcome measures were significantly enhanced by the conjugation of (131)I to Tositumomab.
authors.affiliation: Stanford University, Stanford, California, USA. davisth@mail.nih.gov
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Davis
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Hsu
authors.forename: Mary
authors.initials: M
authors.lastname: Wilkinson
authors.forename: Andrew
authors.initials: A
authors.lastname: Zelenetz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
authors.forename: Stewart
authors.initials: S
authors.lastname: Kroll
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Michael
authors.initials: M
authors.lastname: Goris
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000532:radiotherapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D007457:Iodine Radioisotopes; C119496:tositumomab I-131