A phase I/II trial of iodine-131–tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas

• Published in: Blood Vol. 96; no. 9; pp. 2934 - 2942
• Main Authors: Press, Oliver W., Eary, Janet F., Gooley, Ted, Gopal, Ajay K., Liu, Stephen, Rajendran, Joseph G., Maloney, David G., Petersdorf, Stephen, Bush, Sharon A., Durack, Lawrence D., Martin, Paul J., Fisher, Darrell R., Wood, Brent, Borrow, James W., Porter, Bruce, Smith, Justin P., Matthews, Dana C., Appelbaum, Frederick R., Bernstein, Irwin D.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2000; The Americain Society of Hematology
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Cyclophosphamide - administration & dosage; Etoposide - administration & dosage; Hematopoietic Stem Cell Transplantation; Humans; Iodine Radioisotopes - adverse effects; Iodine Radioisotopes - pharmacokinetics; Iodine Radioisotopes - therapeutic use; Lymphoma, B-Cell - mortality; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell - therapy; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Radioimmunotherapy - adverse effects; Recurrence; Survival Rate; Tissue Distribution; Transplantation, Autologous; Antineoplastic agent; Relapse; Stem cell; Hematopoietic cell; Monoclonal antibody; Autograft; Isomerases; Tositumomab; Lymphoproliferative syndrome; Phase II trial; Immunoradiotherapy; Radiopharmaceuticals; Antimitotic; Human; DNA topoisomerase (ATP-hydrolysing); Enzyme; Iodine 131; Enzyme inhibitor; Etoposide; Malignant hemopathy; B-Lymphocyte; Radiotherapy; Lymphoma; Podophyllotoxine derivatives; Alkylating agent; Oxazaphosphinane derivatives; Chemotherapy; Cyclophosphamide; Treatment; Nitrogen mustard; Phase I trial; Combined treatment
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.9.2934

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 (131I)–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 131I-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 of131I 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 of131I-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.