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Journal of Nuclear Medicine : Official... Nov 2007We retrospectively evaluated our single-center clinical experience with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab for therapy of refractory non-Hodgkin's... (Comparative Study)
Comparative Study
UNLABELLED
We retrospectively evaluated our single-center clinical experience with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab for therapy of refractory non-Hodgkin's lymphoma (NHL). We evaluated the hypothesis that the patient-specific dosing regimen used with (131)I-tositumomab results in less bone marrow toxicity than does the weight-based dosing regimen used with (90)Y-ibritumomab tiuxetan.
METHODS
Thirty-eight patients (25 male and 13 female; median age, 64 y) received radioimmunotherapy for NHL (20 received (90)Y-ibritumomab tiuxetan; 18 received (131)I-tositumomab). Patient and disease characteristics were evaluated to determine whether any were prognostic indicators of short- or long-term clinical response. The 12-wk response rate and clinical and hematologic toxicities attributable to each therapy were assessed. The response rate at 12 wk was correlated with long-term overall survival.
RESULTS
Twenty-six patients received full-radiation-dose radioimmunotherapy and 12 received attenuated doses because of hematologic concerns. The 12-wk overall response rate for all patients was 47%, and the complete response rate was 13%. The 12-wk overall response rate did not significantly differ between the (90)Y-ibritumomab tiuxetan and (131)I-tositumomab groups. Responses at 12 wk were more frequent in patients with normal levels of serum lactate dehydrogenase, no bone marrow involvement, and International Prognostic Index scores of no more than 2 (P < or = 0.04). Grade 3 or 4 thrombocytopenia occurred in 57% and 56% of patients treated with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, respectively. Grade 3 or 4 neutropenia was observed in 57% and 50%, respectively. The time to the absolute neutrophil count nadir was shorter for the (90)Y-ibritumomab tiuxetan group than for the (131)I-tositumomab group (36 +/- 9 vs. 46 +/- 14 d, P = 0.01). The mean percentage decline in platelet count after radioimmunotherapy was greater in the (90)Y-ibritumomab tiuxetan group than in the (131)I-tositumomab group (79% +/- 17% vs. 63% +/- 28%, P = 0.04). Overall survival was longer in responders than in nonresponders 12 wk after therapy (P < or = 0.05).
CONCLUSION
Both (90)Y-ibritumomab tiuxetan and (131)I-tositumomab were well tolerated. We observed response rates at the lower range of those reported in the literature, possibly because of referral bias, dose attenuation, and reasonably liberal acceptance criteria for a patient to receive therapy. Initial response assessments 12 wk after radioimmunotherapy predict longer-term response. (131)I-tositumomab caused significantly less severe declines in platelet counts than did (90)Y-ibritumomab tiuxetan and may be a more appropriate choice for patients with limited bone marrow reserve, but large, randomized, prospective trials are needed to better compare the performance of these 2 treatments.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Bone Marrow; Female; Humans; L-Lactate Dehydrogenase; Lymphoma, B-Cell; Male; Middle Aged; Radioimmunotherapy; Radiopharmaceuticals; Retrospective Studies; Thrombocytopenia
PubMed: 17942813
DOI: 10.2967/jnumed.107.043489 -
Transactions of the American Clinical... 2004Patients with low grade (LG) non-Hodgkin's lymphomas (NHLs) typically have a median survival of 8-10 years during which they sustain a series of responses and relapses... (Review)
Review
Patients with low grade (LG) non-Hodgkin's lymphomas (NHLs) typically have a median survival of 8-10 years during which they sustain a series of responses and relapses to therapy. More than 95% of B-cell NHLs express the CD20 surface antigen, affording opportunities for CD20-directed therapy of NHL. Since 1990, 5 trials have tested the safety and efficacy of the murine CD20 MAb Tositumomab and Iodine I 131 Tositumomab (Bexxar therapeutic regimen) in 250 patients with relapsed, refractory, or transformed LG NHL. The I-131 irradiates MAb-bound cells and those within the path length of the isotope. Response rates were 56% (overall) and 30% (complete). With a median follow-up of 44.6 months, 30% of the patients achieved a long-term, durable response; median time to progressive disease or death was 5 years. Thus, a single treatment with Bexxar may produce durable responses and partially reverse the natural history of LG NHL.
Topics: Antibodies, Monoclonal; Antigens, CD20; Clinical Trials as Topic; Humans; Iodine Radioisotopes; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasm Staging; Radioimmunotherapy; Remission Induction
PubMed: 17060972
DOI: No ID Found -
The Oncologist 2000The concept of targeted therapy for patients with advanced cancer has intrigued researchers for many years. The lymphoid malignancies are particularly good candidates... (Review)
Review
The concept of targeted therapy for patients with advanced cancer has intrigued researchers for many years. The lymphoid malignancies are particularly good candidates for this therapeutic approach, due to the identification of multiple lymphocyte-specific antigens. The recent introduction of rituximab marks the beginning of a new era in the treatment of lymphoid malignancies. Rituximab is one of the most active single agents for patients with refractory indolent lymphoma, producing response rates of approximately 50%, with low toxicity and a brief duration of treatment. Additional uses of rituximab are being evaluated in ongoing clinical trials, and are briefly reviewed. As a first-line agent, responses of approximately 70% are produced in patients with indolent lymphoma, with minimal toxicity. A substantial percentage of patients can be successfully retreated with rituximab, with second remission durations longer than the first remission (14-16 months versus 12 months). Multiple combination regimens using rituximab plus chemotherapy are also being evaluated. Although the role of these combined approaches is incompletely defined, high complete response rates can be obtained, with a higher rate of molecular complete remission (i.e., eradication of detectable bcl-2 rearrangements) than has been observed in patients receiving chemotherapy alone. Rituximab is also being evaluated in other CD20(+) lymphoid malignancies including large-cell lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Within the next 12 months, several additional monoclonal antibodies will be available for the treatment of lymphoid malignancies. These include the radioimmunoconjugates tositumomab (Bexxar) and ibritumomab (Zevalin), as well as Campath-1H (anti-CD52) monoclonal antibody. Early clinical data with each of these agents are also briefly reviewed.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Clinical Trials as Topic; Humans; Immunoconjugates; Lymphoma; Rituximab; Yttrium Radioisotopes
PubMed: 11040273
DOI: 10.1634/theoncologist.5-5-376 -
Journal of Nuclear Medicine Technology Sep 2002This article briefly describes the concept of radioimmunotherapy and treatment of non-Hodgkin's lymphoma by a new radiopharmaceutical that uses this technique. The... (Review)
Review
This article briefly describes the concept of radioimmunotherapy and treatment of non-Hodgkin's lymphoma by a new radiopharmaceutical that uses this technique. The rationale for such an approach is reviewed, and some of the practical consequences for technologists are examined. These include the idea of performing individually customized dosimetry and using relatively high (131)I doses on an outpatient basis. After reading this article, the nuclear medicine technologist should be able to (a) describe radioimmunotherapy and its advantages, (b) explain why treatment of non-Hodgkin's lymphoma is enhanced by this technique, (c) understand the role of the predose study and its use in determining the therapeutic dose, and (d) recognize the radiation safety issues involved with the therapeutic dose administration and patient release criteria.
Topics: Aftercare; Antibodies, Monoclonal; Dose-Response Relationship, Radiation; Humans; Infusions, Intravenous; Lymphoma, B-Cell; Patient Discharge; Quality Control; Radioimmunotherapy; Radionuclide Imaging; Radiotherapy Dosage; Radiotherapy, Adjuvant; Sensitivity and Specificity; Treatment Outcome; Whole-Body Counting
PubMed: 12186959
DOI: No ID Found -
Exploration of Targeted Anti-tumor... 2024Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces... (Review)
Review
Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventional treatment. The purpose of this review is to summarize the current progress of RIT for treating non-Hodgkin's lymphoma (NHL) based on recent preclinical and clinical studies. The efficacy of RIT targeting the B-lymphocyte antigen cluster of differentiation 20 (CD20) has been demonstrated in clinical trials. Two radioimmunoconjugates targeting CD20, yttrium-90 (Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Although these two radioimmunoconjugates are effective and least toxic, they have not achieved popularity due to increasing access to novel therapies and the complexity of their delivery process. RIT is constantly evolving with the identification of novel targets and novel therapeutic strategies using newer radionuclides such as alpha-particle isotopes. Alpha-particles show very short path lengths and high linear energy transfer. These characteristics provide increased tumor cell-killing activities and reduced non-specific bystander responses on normal tissue. This review also discusses reviewed pre-targeted RIT (PRIT) and immuno-positron emission tomography (PET). PRIT potentially increases the dose of radionuclide delivered to tumors while toxicities to normal tissues are limited. Immuno-PET is a molecular imaging tracer that combines the high sensitivity of PET with the specific targeting capability of mAb. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response.
PubMed: 38464386
DOI: 10.37349/etat.2024.00213 -
TheScientificWorldJournal 2014Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies... (Review)
Review
Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments) or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by (90)Y-ibritumomab tiuxetan (Zevalin) and (131)I-tositumomab (Bexxar), both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment.
Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Antineoplastic Agents; Humans; Immunoconjugates; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Neoplasms; Radioimmunotherapy; Yttrium Radioisotopes
PubMed: 25379535
DOI: 10.1155/2014/492061 -
Best Practice & Research. Clinical... Jun 2012Mantle cell lymphoma (MCL), though characterized by the chromosomal translocation t(11; 14) (q13; q32), is a heterogeneous disease. Often termed an aggressive lymphoma... (Review)
Review
Mantle cell lymphoma (MCL), though characterized by the chromosomal translocation t(11; 14) (q13; q32), is a heterogeneous disease. Often termed an aggressive lymphoma in the U.S., but included in indolent lymphoma trials in Europe, MCL is not curable with standard immuno-chemotherapy. There is no single standard initial therapy for this disease. Although standard lymphoma therapies yield high response rates, relapse is inevitable. Unmet needs in MCL include better induction therapy, consolidation treatments to prolong first remission and better therapeutic options for relapsed disease. In this review, we evaluate the role of radioimmunotherapy (RIT) in MCL, a novel strategy combining monoclonal antibodies with radioisotopes to deliver radiation directly to tumour tissue, both in the frontline and relapsed setting.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Clinical Trials as Topic; Drug Administration Schedule; Humans; Lymphoma, Mantle-Cell; Molecular Targeted Therapy; Radioimmunotherapy; Radioisotopes; Recurrence; Remission Induction
PubMed: 22687456
DOI: 10.1016/j.beha.2012.04.004 -
Journal of Nuclear Medicine : Official... Jan 2023We studied the feasibility of using the α-emitting Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse...
We studied the feasibility of using the α-emitting Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse model. A highly lethal SCID mouse model of minimal-tumor-burden disseminated non-Hodgkin lymphoma (NHL) was established using human Raji lymphoma cells transfected to express the luciferase reporter. In vitro and in vivo radioimmunotherapy experiments were conducted. Single- and multiple-dose regimens were explored, and results with Bi-rituximab were compared with various controls, including no treatment, free Bi radiometal, unlabeled rituximab, and Bi-labeled anti-HER2/ (non-CD20-specific antibody). Bi-rituximab was also compared in vivo with the low-energy β-emitter I-tositumomab and the high-energy β-emitter Y-rituximab. In vitro studies showed dose-dependent target-specific killing of lymphoma cells with Bi-rituximab. Multiple in vivo studies showed significant and specific tumor growth delays with Bi-rituximab versus free Bi, Bi-labeled control antibody, or unlabeled rituximab. Redosing of Bi-rituximab was more effective than single dosing. With a single dose of therapy given 4 d after intravenous tumor inoculation, disease in all untreated controls, and in all mice in the 925-kBq Y-rituximab group, progressed. With 3,700 kBq of Bi-rituximab, 75% of the mice survived and all but 1 survivor was cured. With 2,035 kBq of I-tositumomab, 75% of the mice were tumor-free by bioluminescent imaging and 62.5% survived. Cure of micrometastatic NHL is achieved in most animals treated 4 d after intravenous tumor inoculation using either Bi-rituximab or I-tositumomab, in contrast to the lack of cures with unlabeled rituximab or Y-rituximab or if there was a high tumor burden before radioimmunotherapy. α-emitter-labeled anti-CD20 antibodies are promising therapeutics for NHL, although a longer-lived α-emitter may be of greater efficacy.
Topics: Mice; Humans; Animals; Rituximab; Mice, SCID; Antibodies, Monoclonal; Lymphoma, B-Cell; Antineoplastic Agents; Lymphoma, Non-Hodgkin; Lymphoma; Radioimmunotherapy; Antigens, CD20
PubMed: 35981897
DOI: 10.2967/jnumed.122.263962 -
Journal of the American Academy of... Nov 2013Pruritus has been anecdotally described in association with targeted cancer therapies. The risk of pruritus has not been systematically ascertained. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pruritus has been anecdotally described in association with targeted cancer therapies. The risk of pruritus has not been systematically ascertained.
OBJECTIVE
A systematic review and meta-analysis of the literature was conducted for axitinib, cetuximab, dasatinib, erlotinib, everolimus, gefitinib, imatinib, ipilimumab, lapatinib, nilotinib, panitumumab, pazopanib, rituximab, sorafenib, temsirolimus, tositumomab, vandetanib, and vemurafenib.
METHODS
Databases from PubMed, Web of Science (January 1998 through July 2012), and American Society of Clinical Oncology abstracts (2004 through 2012) were searched. Incidence and relative risk of pruritus were calculated using random- or fixed-effects model.
RESULTS
The incidences of all-grade and high-grade pruritus were 17.4% (95% confidence interval 16.0%-19.0%) and 1.4% (95% confidence interval 1.2%-1.6%), respectively. There was an increased risk of all-grade pruritus (relative risk 2.90 [95% confidence interval 1.76-4.77, P < .001]) and variation among different drugs (P < .001).
LIMITATIONS
The reporting of pruritus may vary, resulting from concomitant medications, comorbidities, and underlying malignancies. We found a higher incidence of pruritus in patients with solid tumors, concordant with those targeted therapies with the highest pruritus incidences.
CONCLUSION
There is a significant risk of developing pruritus in patients receiving targeted therapies. To prevent suboptimal dosing and decreased quality of life, patients should be counseled and treated against this untoward symptom.
Topics: Drug Eruptions; Humans; Molecular Targeted Therapy; Neoplasms; Pruritus
PubMed: 23981682
DOI: 10.1016/j.jaad.2013.06.038 -
Journal of Nuclear Medicine : Official... Jul 2014The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphoma patients after (131)I-tositumomab...
UNLABELLED
The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphoma patients after (131)I-tositumomab radioimmunotherapy for potential use in treatment planning.
METHODS
Tumor-absorbed dose measures were estimated for 130 tumors in 39 relapsed or refractory non-Hodgkin lymphoma patients by coupling SPECT/CT imaging with the Dose Planning Method (DPM) Monte Carlo code. Equivalent biologic effect was calculated to assess the biologic effects of nonuniform absorbed dose including the effects of the unlabeled antibody. Evaluated nondosimetric covariates included histology, presence of bulky disease, and prior treatment history. Tumor level outcome was based on volume shrinkage assessed on follow-up CT. Patient level outcome measures were overall response (OR), complete response (CR), and progression-free survival (PFS), determined from clinical assessments that included PET/CT.
RESULTS
The estimated mean tumor-absorbed dose had a median value of 275 cGy (range, 94-711 cGy). A high correlation was observed between tracer-predicted and therapy-delivered mean tumor-absorbed doses (P < 0.001; r = 0.85). In univariate tumor-level analysis, tumor shrinkage correlated significantly with almost all of the evaluated dosimetric factors, including equivalent biologic effect. Regression analysis showed that OR, CR, and PFS were associated with the dosimetric factors and equivalent biologic effect. Both mean tumor-absorbed dose (P = 0.025) and equivalent biologic effect (P = 0.035) were significant predictors of PFS whereas none of the nondosimetric covariates were found to be statistically significant factors affecting PFS. The most important finding of the study was that in Kaplan-Meier curves stratified by mean dose, longer PFS was observed in patients receiving mean tumor-absorbed doses greater than 200 cGy than in those receiving 200 cGy or less (median PFS, 13.6 vs. 1.9 mo for the 2 dose groups; log-rank P < 0.0001).
CONCLUSION
A higher mean tumor-absorbed dose was significantly predictive of improved PFS after (131)I-tositumomab radioimmunotherapy. Hence tumor-absorbed dose, which can be estimated before therapy, can potentially be used to design radioimmunotherapy protocols to improve efficacy.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Disease-Free Survival; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Monte Carlo Method; Precision Medicine; Radiation Dosage; Radioimmunotherapy; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Tumor Burden
PubMed: 24842891
DOI: 10.2967/jnumed.113.136044