title: Phase 1 study of radiosensitization using bortezomib in patients with relapsed non-Hodgkin lymphoma receiving radioimmunotherapy with 131I-tositumomab.
abstract: Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin lymphomas (NHLs), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This phase 1 dose-escalation study evaluated escalating doses of bortezomib combined with 131I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. The maximum tolerated dose (MTD) was determined to be 0.9 mg/m2 bortezomib, in combination with a standard dose of 75 cGy 131I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CRs), with 82% CR in patients with follicular lymphoma (FL). At a median follow-up of 7 months, median progression-free survival was 7 months, and seven of 11 patients with FL remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with 131I-tositumomab with promising response rates.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College , New York, NY , USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Elstrom
authors.forename: Jia
authors.initials: J
authors.lastname: Ruan
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.forename: Daniel
authors.initials: D
authors.lastname: Lebovic
authors.forename: Joseph
authors.initials: J
authors.lastname: Osborne
authors.forename: Stanley
authors.initials: S
authors.lastname: Goldsmith
authors.forename: June
authors.initials: J
authors.lastname: Greenberg
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Anca
authors.initials: A
authors.lastname: Avram
authors.forename: Ryan
authors.initials: R
authors.lastname: Putman
authors.forename: Erica
authors.initials: E
authors.lastname: Chapman
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Kent
authors.initials: K
authors.lastname: Griffith
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069286:Bortezomib / Q000009:adverse effects / Q000627:therapeutic use*; D023341:Chills / Q000209:etiology; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000209:etiology; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D012074:Remission Induction; D013921:Thrombocytopenia / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents; D000069286:Bortezomib; C119496:tositumomab I-131
keywords: Lymphoma; proteasome; radioimmunotherapy; radiosensitization
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