title: Initial clinical experience evaluating Yttrium-90-chimeric T84.66 anticarcinoembryonic antigen antibody and autologous hematopoietic stem cell support in patients with carcinoembryonic antigen-producing metastatic breast cancer.
abstract: cT84.66 is a human/murine IgG1 with high affinity and specificity for carcinoembryonic antigen (CEA). An earlier Phase I trial defined the maximum tolerated dose for 90Y-diethylenetriaminepentaacetic acid (DTPA)-cT84.66 at 22 mCi/m2. Dose-limiting toxicities were reversible leukopenia and thrombocytopenia. The purpose of this Phase I trial was to evaluate the feasibility and toxicities of administering higher activities of 90Y-DTPA-cT84.66 with stem cell support in patients with CEA-producing breast cancer. Patients with CEA-producing breast cancer refractory to standard therapies underwent peripheral stem cell collection followed by infusion of 111indium-DTPA-cT84.66. Those patients demonstrating tumor targeting received a single therapy dose of 90Y-DTPA-cT84.66, followed by Ca-DTPA infusion for 72 h posttherapy. Stem cells were reinfused following a divided schedule. To date, seven patients have been accrued to this trial. Each patient received an imaging dose of (111)In-cT84.66. Six patients demonstrated tumor imaging and received a single cycle of 90Y-cT84.66 at 15 mCi/m2 (three patients) and 22.5 mCi/m2 (three patients). One patient did not demonstrate tumor imaging and was not treated. At these administered activities, 90Y-cT84.66 was well tolerated. No dose-limiting toxicities have been observed. All patients demonstrated hematopoietic recovery after stem cell infusion. One patient demonstrated stable disease for 4 months; one patient had stable disease and reduction of bone pain for 3 months; and a third patient experienced >50% reduction of an ovarian metastasis, resolution of malignant pleural effusion, stable pleural metastases, and stable bone scan for 14 months. Preliminary results from this ongoing Phase I trial are promising and demonstrate the feasibility and potential for antitumor effects of stem cell supported 90Y-cT84.66 therapy in patients with CEA-producing breast cancers.
authors.affiliation: Division of Radiation Oncology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: T
authors.initials: T
authors.lastname: Odom-Maryon
authors.forename: L E
authors.initials: LE
authors.lastname: Williams
authors.forename: A
authors.initials: A
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Yamauchi
authors.forename: A M
authors.initials: AM
authors.lastname: Wu
authors.forename: P
authors.initials: P
authors.lastname: Yazaki
authors.forename: S
authors.initials: S
authors.lastname: Wilczynski
authors.forename: J E
authors.initials: JE
authors.lastname: Shively
authors.forename: S
authors.initials: S
authors.lastname: Forman
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: A A
authors.initials: AA
authors.lastname: Raubitschek
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000276:immunology*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D051379:Mice; D004369:Pentetic Acid / Q000627:therapeutic use; D011863:Radioimmunoassay / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D015021:Yttrium Radioisotopes; D004369:Pentetic Acid