title: A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas.
abstract: Relapsed B-cell lymphomas are incurable with conventional chemotherapy and radiation therapy, although a fraction of patients can be cured with high-dose chemoradiotherapy and autologous stem-cell transplantation (ASCT). We conducted a phase I/II trial to estimate the maximum tolerated dose (MTD) of iodine 131 ((131)I)-tositumomab (anti-CD20 antibody) that could be combined with etoposide and cyclophosphamide followed by ASCT in patients with relapsed B-cell lymphomas. Fifty-two patients received a trace-labeled infusion of 1.7 mg/kg (131)I-tositumomab (185-370 MBq) followed by serial quantitative gamma-camera imaging and estimation of absorbed doses of radiation to tumor sites and normal organs. Ten days later, patients received a therapeutic infusion of 1.7 mg/kg tositumomab labeled with an amount of (131)I calculated to deliver the target dose of radiation (20-27 Gy) to critical normal organs (liver, kidneys, and lungs). Patients were maintained in radiation isolation until their total-body radioactivity was less than 0.07 mSv/h at 1 m. They were then given etoposide and cyclophosphamide followed by ASCT. The MTD of (131)I-tositumomab that could be safely combined with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide delivered 25 Gy to critical normal organs. The estimated overall survival (OS) and progression-free survival (PFS) of all treated patients at 2 years was 83% and 68%, respectively. These findings compare favorably with those in a nonrandomized control group of patients who underwent transplantation, external-beam total-body irradiation, and etoposide and cyclophosphamide therapy during the same period (OS of 53% and PFS of 36% at 2 years), even after adjustment for confounding variables in a multivariable analysis.
authors.affiliation: Departments of Medicine, Pathology, Pediatrics, Radiology, Biological Structure, and Biostatistics, the University of Washington, Seattle, WA 98195, USA.
authors.forename: O W
authors.initials: OW
authors.lastname: Press
authors.forename: J F
authors.initials: JF
authors.lastname: Eary
authors.forename: T
authors.initials: T
authors.lastname: Gooley
authors.forename: A K
authors.initials: AK
authors.lastname: Gopal
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: J G
authors.initials: JG
authors.lastname: Rajendran
authors.forename: D G
authors.initials: DG
authors.lastname: Maloney
authors.forename: S
authors.initials: S
authors.lastname: Petersdorf
authors.forename: S A
authors.initials: SA
authors.lastname: Bush
authors.forename: L D
authors.initials: LD
authors.lastname: Durack
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: D R
authors.initials: DR
authors.lastname: Fisher
authors.forename: B
authors.initials: B
authors.lastname: Wood
authors.forename: J W
authors.initials: JW
authors.lastname: Borrow
authors.forename: B
authors.initials: B
authors.lastname: Porter
authors.forename: J P
authors.initials: JP
authors.lastname: Smith
authors.forename: D C
authors.initials: DC
authors.lastname: Matthews
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: I D
authors.initials: ID
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D016499:Radioimmunotherapy / Q000009:adverse effects; D012008:Recurrence; D015996:Survival Rate; D014018:Tissue Distribution; D014182:Transplantation, Autologous
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D005047:Etoposide; D003520:Cyclophosphamide; C119496:tositumomab I-131