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Expert Opinion on Biological Therapy Apr 2005The CD20 antigen has become a major therapeutic target in the management of follicular and other B cell non-Hodgkin's lymphomas. The murine monoclonal antibody,... (Review)
Review
The CD20 antigen has become a major therapeutic target in the management of follicular and other B cell non-Hodgkin's lymphomas. The murine monoclonal antibody, tositumomab, on binding CD20, is able to induce antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis. In addition, when radioiodinated, the antibody exploits the tumour's sensitivity to ionising radiation by direct targeting of the malignant cell. Tositumomab and Iodine (I(131)) tositumomab (Bexxar, GlaxoSmithKline, Philadelphia, PA, USA) is administered in two steps. The dosimetric step determines individual patient pharmacokinetics, allowing a patient- specific dose to be calculated. This is followed by the therapeutic step, with administration of the therapeutic dose between 7 and 14 days after the dosimetric dose. Over a decade's worth of experience in clinical trials has determined the efficacy and safety of the regimen in a variety of clinical circumstances; establishment of exactly where the regimen fits amongst the algorithm for the management of follicular lymphoma continues.
Topics: Animals; Antibodies, Monoclonal; Clinical Trials as Topic; Humans; Iodine Radioisotopes; Lymphoma, Follicular; Radioimmunotherapy
PubMed: 15934835
DOI: 10.1517/14712598.5.4.577 -
Seminars in Oncology Apr 2003Radioimmunotherapy (RIT) is a promising emerging therapy for non-Hodgkin's lymphoma and may ultimately prove useful in the treatment of other tumors. The most... (Review)
Review
Radioimmunotherapy (RIT) is a promising emerging therapy for non-Hodgkin's lymphoma and may ultimately prove useful in the treatment of other tumors. The most extensively investigated RIT agent is tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA, and GlaxoSmithKline, Philadelphia, PA) which has been administered to over 1,000 patients during the past 9 years. As with most drugs, there is considerable interpatient variability in the clearance rate (or total body residence time) of radioimmunoconjugates. The clearance rate of iodine I 131 tositumomab in clinical trials has varied by as much as five-fold. The advantage of RIT with iodine-131, which emits both gamma photons and beta particles, is that by scanning it allows for the determination of the patient-specific total body residence time by the administration of a trace-labeled dose of the radionuclide (ie, dosimetric dose). By administration of the dosimetric (trace-labeled) dose, and determination of the patient's residence time (a measure of how long the radionuclide is retained in the body), the therapeutic dose can be precisely adjusted to maximize the therapeutic effect and minimize toxicity. Tositumomab and iodine I 131 tositumomab is a specific therapeutic at two levels: first, it specifically targets the tumor, delivering a log or more radiation to tumor compared with the rest of the body; and second, the administered dose of radioactivity is patient-specific. The paradigm of a targeted drug with a patient-specific dose may become more routine as targeted therapies are further developed along with better assays to directly measure drug levels. For the present, whole-body dosimetry is routinely applied for RIT with tositumomab and iodine I 131 tositumomab and has proven to be a reliable method to determine the patient-specific maximally tolerated therapeutic radiation dose to maximize efficacy while minimizing organ and bone marrow toxicity.
Topics: Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Humans; Immunoconjugates; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Radioimmunotherapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 12728405
DOI: 10.1053/sonc.2003.23799 -
Oncology Nursing Forum Nov 2004To review radioimmunotherapy approaches for low-grade non-Hodgkin lymphoma (NHL) with a focus on tositumomab and iodine-131 tositumomab (Bexxar, Corixa Corporation,... (Review)
Review
PURPOSE/OBJECTIVES
To review radioimmunotherapy approaches for low-grade non-Hodgkin lymphoma (NHL) with a focus on tositumomab and iodine-131 tositumomab (Bexxar, Corixa Corporation, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA). Nursing implications for Bexxar therapy are reviewed, including radiation safety, patient education, and the management of therapy-related toxicities.
DATA SOURCES
Journal articles, published research data, and clinical experience.
DATA SYNTHESIS
The Bexxar treatment regimen (using an anti-CD20 antibody) consists of a dosimetric administration followed 7-14 days later by a patient-specific therapeutic administration. Infusion-related adverse events and myelosuppression are manageable. Patient and caregiver education regarding the benefits of radioimmunotherapy, treatment protocols, and radiation safety precautions is necessary.
CONCLUSIONS
Bexxar therapy represents an important new treatment option for patients with low-grade NHL and can be administered on an outpatient basis.
IMPLICATIONS FOR NURSING
Nurses play a vital role in the success of a Bexxar therapy program by providing patient and caregiver education, patient monitoring, and coordinating treatment schedules.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Clinical Trials as Topic; Family Health; Health Education; Humans; Lymphoma, Non-Hodgkin; Patient Education as Topic; Radiation Protection; Radioimmunotherapy
PubMed: 15547634
DOI: 10.1188/04.ONF.1119-1126 -
AJNR. American Journal of Neuroradiology Apr 2011Tositumomab and iodine I 131 tositumomab (Bexaar) therapeutic regimen targets monoclonal antibodies against the CD20 antigen expressed in non-Hodgkin lymphoma. This... (Review)
Review
Tositumomab and iodine I 131 tositumomab (Bexaar) therapeutic regimen targets monoclonal antibodies against the CD20 antigen expressed in non-Hodgkin lymphoma. This article reviews the mechanism of action and clinical indications for this regimen.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Humans; Lymphoma, Non-Hodgkin; Radioimmunotherapy; Tomography, X-Ray Computed
PubMed: 21436340
DOI: 10.3174/ajnr.A2593 -
The Quarterly Journal of Nuclear... Apr 2011Radioimmunotherapy involves the use of radiolabeled monoclonal antibodies (MAbs) to treat malignancy. The therapeutic effect is determined by the radiopharmaceutical,... (Review)
Review
Radioimmunotherapy involves the use of radiolabeled monoclonal antibodies (MAbs) to treat malignancy. The therapeutic effect is determined by the radiopharmaceutical, the radiation absorbed dose and previous treatments. There are currently two approved radiopharmaceuticals for the treatment of B-cell lymphoma - the (90)Y-labeled ibritumomab and the (131)I-labeled tositumomab. Both are directed against CD20, albeit not against the same epitope. This paper summarizes current results of dose-responses for normal tissues and tumours of [(131)I]tositumomab and [(90)Y]ibritumomab tiuxetan, discusses them in the context of dosimetry methods used and highlights the assumptions being made in the different dosimetry methodologies. Moreover, we wish to point at the possibility of performing low-cost therapy bremsstrahlung imaging for [(90)Y]ibritumomab tiuxetan to confirm biodistribution, and possibly also for dosimetric calculations.
Topics: Antibodies, Monoclonal; Antigens, CD20; Bone Marrow; Dose-Response Relationship, Radiation; Female; Humans; Iodine Radioisotopes; Lymphoma, B-Cell; Male; Radioimmunotherapy; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Yttrium Radioisotopes
PubMed: 21386787
DOI: No ID Found -
International Journal of Radiation... 2006Iodine-131 (I-131) tositumomab (Bexxar; GlaxoSmithKline, Research Triangle Park, NC) is one of two recently approved radiolabeled antibodies directed against the CD20... (Review)
Review
Iodine-131 (I-131) tositumomab (Bexxar; GlaxoSmithKline, Research Triangle Park, NC) is one of two recently approved radiolabeled antibodies directed against the CD20 surface antigen found on normal B cells and in more than 95% of B cell non-Hodgkin's lymphoma. The compound itself is formulated as an IgG2a immunoglobulin radiolabeled with the mixed beta/gamma emitter I-131. Multicenter clinical trials have repeatedly shown impressive clinical responses (20-40% complete response rates and 60-80% overall response rates) in the patient groups for whom this treatment is indicated. Treatment-related toxicity is generally extremely mild and typically involves only reversible hematopoietic suppression and (in some cases) a risk of treatment-induced hypothyroidism. Owing to the radiation safety concerns necessitated by the clinical use of this targeted radiopharmaceutical, it is important for radiation oncology departments wishing to participate in the care of these patients to establish methodologies and standard operating procedures for safe and efficient departmental use. This summary reviews the pertinent background information related to the current clinical experience with I-131 tositumomab and highlights some of the major opportunities for the participation of radiation oncology in the patient evaluation and treatment process. I-131 tositumomab provides an excellent example of the way in which the increasingly important new field of "targeted therapy" intersects with the practice of clinical radiotherapy. The author contends that it will be worth the time and effort involved in establishing a firm basis for the development of a comprehensive program for systemic targeted radiopharmaceutical therapies (STaRT) within the radiation medicine domain.
Topics: Antibodies, Monoclonal; Antigens, CD20; Humans; Metabolic Clearance Rate; Multicenter Studies as Topic; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Radiation Oncology; Radioimmunotherapy
PubMed: 16979436
DOI: 10.1016/j.ijrobp.2005.06.002 -
The Quarterly Journal of Nuclear... Dec 2004Iodine [(131)I] tositumomab, administered in combination with unlabelled tositumomab, is a novel radioimmunotherapeutic regimen that targets the CD20 antigen present on... (Review)
Review
Iodine [(131)I] tositumomab, administered in combination with unlabelled tositumomab, is a novel radioimmunotherapeutic regimen that targets the CD20 antigen present on normal and malignant B-cells. The efficacy and safety of the non-myeloablative regimen has been demonstrated in follicular and transformed follicular lymphoma over the last decade in a series of clinical studies, culminating in FDA approval in June 2003. In patients with relapsed or refractory disease some remissions have proven to be durable, and frequently longer in duration than previously administered chemotherapeutic agents. As initial therapy for advanced stage follicular lymphoma, response rates are particularly impressive. Toxicity has been principally haematological, with a single nadir at 4-6 weeks post-therapy. Administration is free of many of the side effects of conventional chemotherapy, although concerns about the long term risk of therapy related myelodysplasia persist. The challenge now comes from deciding the correct place of iodine [(131)I] tositumomab in treatment algorithms for follicular and other ''indolent'' lymphomas. Sequential administration after chemotherapy is being actively investigated, as is its role in myeloablative therapy. Issues of cost-benefit aside, it is a significant development in the therapy of these ''chronic'' malignancies.
Topics: Antibodies, Monoclonal; Clinical Trials as Topic; Humans; Lymphoma, Follicular; Practice Patterns, Physicians'; Radiopharmaceuticals; Treatment Outcome
PubMed: 15640794
DOI: No ID Found -
Journal of Nuclear Medicine : Official... Jul 2023In the early 2000s, major clinical trials provided evidence of a favorable outcome from antibody-mediated radioimmunotherapy for hematologic neoplasms, which then led to...
In the early 2000s, major clinical trials provided evidence of a favorable outcome from antibody-mediated radioimmunotherapy for hematologic neoplasms, which then led to Food and Drug Administration approval. For instance, the theranostic armamentarium for the referring hematooncologist now includes Y-ibritumomab tiuxetan for refractory low-grade follicular lymphoma or transformed B-cell non-Hodgkin lymphoma, as well as I-tositumomab for rituximab-refractory follicular lymphoma. Moreover, the first interim results of the SIERRA phase III trial reported beneficial effects from the use of I-anti-CD45 antibodies (Iomab-B) in refractory or relapsed acute myeloid leukemia. During the last decade, the concept of theranostics in hematooncology has been further expanded by C-X-C motif chemokine receptor 4-directed molecular imaging. Beyond improved detection rates of putative sites of disease, C-X-C motif chemokine receptor 4-directed PET/CT also selects candidates for radioligand therapy using β-emitting radioisotopes targeting the identical chemokine receptor on the lymphoma cell surface. Such image-piloted therapeutic strategies provided robust antilymphoma efficacy, along with desired eradication of the bone marrow niche, such as in patients with T- or B-cell lymphoma. As an integral part of the treatment plan, such radioligand therapy-mediated myeloablation also allows one to line up patients for stem cell transplantation, which leads to successful engraftment during the further treatment course. In this continuing education article, we provide an overview of the current advent of theranostics in hematooncology and highlight emerging clinical applications.
Topics: Humans; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Precision Medicine; Positron Emission Tomography Computed Tomography; Lymphoma, B-Cell; Radioimmunotherapy; Yttrium Radioisotopes
PubMed: 37290799
DOI: 10.2967/jnumed.122.265199 -
Clinical Lymphoma Dec 2001Radioimmunotherapy with anti-CD20 antibodies is a promising treatment approach for relapsed low-grade non-Hodgkin's lymphoma. Under revised Nuclear Regulatory Commission... (Review)
Review
Radioimmunotherapy with anti-CD20 antibodies is a promising treatment approach for relapsed low-grade non-Hodgkin's lymphoma. Under revised Nuclear Regulatory Commission regulations (May 1997), patients may be released following treatment provided the maximum dose to any individual is not likely to exceed 500 mrem. Non-Hodgkin's lymphoma patients have been studied to evaluate radiation exposure to caregivers/family members after outpatient treatment with tositumomab and iodine I 131 tositumomab (Bexxar therapy). Estimates of total radiation doses to individuals expected to be maximally exposed to patients posttreatment have revealed that the doses should be within revised guidelines. In a University of Nebraska Medical Center study, the predicted total radiation doses (based on patient dose rate at 1 meter) ranged from 95-423 mrem. Family members were provided radiation-monitoring devices to directly monitor radiation exposure. Measured doses ranged from 10-409 mrem. In this and other studies, estimated and measured dose equivalents to maximally exposed individuals were below 500 mrem. Measured doses were, in most instances, lower than those predicted by patient-specific calculations, thus confirming the validity of the calculated dose predictions. Therefore, radioimmunotherapy with tositumomab and iodine I 131 tositumomab can be safely conducted on an outpatient basis.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Feasibility Studies; Humans; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Patient Selection; Radiation Monitoring; Radiation Protection; Radioimmunotherapy; Radiotherapy Dosage; Safety
PubMed: 11779293
DOI: 10.3816/clm.2001.n.022 -
Journal of Nuclear Medicine : Official... Nov 2015The tositumomab/(131)I-tositumomab radioimmunotherapy regimen is administered as a dosimetric dose followed by a therapeutic dose. The biodistribution of the dosimetric... (Observational Study)
Observational Study
UNLABELLED
The tositumomab/(131)I-tositumomab radioimmunotherapy regimen is administered as a dosimetric dose followed by a therapeutic dose. The biodistribution of the dosimetric dose is assessed by quantitative calculations of whole-body residence time (TBRT) and visual examination of whole-body γ-camera images, to determine the administered radioactivity dose and whether a therapeutic dose can be administered. We investigated whether altered biodistribution of (131)I-tositumomab could be identified using quantitative TBRT.
METHODS
BioClinica, Inc., provided γ-camera images to an independent reviewer to assess altered (131)I-tositumomab biodistribution in patients reported to a registry.
RESULTS
Of 2,649 therapeutic doses, 5 (0.2%) were cancelled because of altered biodistribution as determined by γ-camera images and TBRT. Of these, 3 γ-camera images were assessed by the independent reviewer; one showed altered biodistribution (0.04%) and was in agreement with the TBRT on-site calculation.
CONCLUSION
TBRT alone should be used to determine altered biodistribution and hence whether to administer the therapeutic dose.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Dose-Response Relationship, Radiation; Humans; Iodine Radioisotopes; Lung; Lymphoma, Non-Hodgkin; Radionuclide Imaging; Retrospective Studies; Tissue Distribution; Whole Body Imaging
PubMed: 26338897
DOI: 10.2967/jnumed.115.156190