title: Phase I study of radioimmunotherapy with an anti-CD20 murine radioimmunoconjugate ((90)Y-ibritumomab tiuxetan) in relapsed or refractory indolent B-cell lymphoma.
abstract: We conducted a phase I study to evaluate the safety and efficacy of radioimmunotherapy with yttrium-90-ibritumomab tiuxetan (Y2B8) in Japanese patients with relapsed or refractory indolent B-cell lymphoma. Indium-111-labeled ibritumomab tiuxetan (In2B8; 3.5 or 5 mCi [129.5 or 185 MBq]) was administered on day 1, followed by serial gamma-camera imaging to investigate the distribution of In2B8 in the whole body of patients and to judge the feasibility of Y2B8 administration. Y2B8 with a dose of 0.3 mCi/kg (11.1 MBq/kg) or 0.4 mCi/kg (14.8 MBq/kg) was administered on day 8. Grade 4 neutropenia and grade 3 thrombocytopenia were observed in three of nine of the patients evaluated for safety. Critical toxicities (prolonged thrombocytopenia or severe non-hematological toxicities) were observed in two of six patients in the 0.4 mCi/kg (14.8 MBq/kg) dose group but were not seen in any of the three patients in the 0.3 mCi/kg (11.1 MBq/kg) dose group. The non-hematological toxicities of the nine patients were of grade 2 or less, except in two patients who had been heavily treated previously. They experienced critical toxicities such as infection, diarrhea, hyponatremia and prolonged thrombocytopenia, as well as other frequent grade 2 non-hematological toxicities. Although the pharmacokinetic profiles were similar to those in the US study, one of the two patients was clarified retrospectively as showing abnormal biodistribution of In2B8 in the bone marrow, as judged by an independent third party panel of radiologists. Five of the 10 participants achieved complete responses or unconfirmed complete responses and two partial responses. In conclusion, the recommended dose of Y2B8 for the subsequent phase II study for Japanese patients is 0.4 mCi/kg (14.8 MBq/kg). This dose of radioimmunotherapy was feasible when patients with altered biodistribution of In2B8 were excluded, and it was highly effective. (Cancer Sci 2005; 96: 903-910).
authors.affiliation: Hematology and Stem Cell Transplantation Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shoji
authors.initials: S
authors.lastname: Terui
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Itoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Terauchi
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Usubuchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nawano
authors.forename: Naohiro
authors.initials: N
authors.lastname: Sekiguchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
authors.forename: Taku
authors.initials: T
authors.lastname: Seriu
authors.forename: Masaki
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000633:toxicity*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016499:Radioimmunotherapy / Q000009:adverse effects*; D012008:Recurrence; D015203:Reproducibility of Results; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan