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Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Células Madre de Sangre Periférica , Ciclofosfamida/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Incidencia , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Donante no EmparentadoRESUMEN
These NCCN Guidelines Insights highlight the important updates/changes specific to the management of relapsed or progressive disease in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma. These changes include the addition of new regimens as options for salvage therapy and strategies to mitigate the adverse effects and risks associated with newer regimens for the treatment of multiple myeloma.
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Antineoplásicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Terapia Recuperativa , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorhidrato de Bendamustina , Ácidos Borónicos/administración & dosificación , Bortezomib , Dexametasona/administración & dosificación , Progresión de la Enfermedad , Humanos , Ácidos Hidroxámicos/administración & dosificación , Lenalidomida , Mieloma Múltiple/complicaciones , Compuestos de Mostaza Nitrogenada/administración & dosificación , Oligopéptidos/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/terapia , Pirazinas/administración & dosificación , Recurrencia , Talidomida/administración & dosificación , Talidomida/análogos & derivados , VorinostatRESUMEN
Purpose: Various radiation therapy (RT) dose/fractionation schedules are acceptable for palliation in multiple myeloma. Nine years of single-institution RT experience were reviewed to determine the influence of dose/fractionation and other factors pertinent to individualizing therapy. Methods and Materials: In total, 152 items were identified from Current Procedural Terminology codes for multiple myeloma treatment from 2012 through June 30, 2021. After exclusions, 205 sites of radiation in 94 patients were reviewed. Data were captured from treatment planning and clinical records. To statistically assess the association between biological effective dose (BED10) and variables of interest, BED was first dichotomized to <24 Gy versus ≥24 Gy. Multivariate analysis used SAS software and a generalized estimating equation approach to account for multiple observations per patient. Results: Fractions of 1.8 to 8 Gy were used in 1 to 25 fractions. Most patients had no significant toxicity. Grade 1 toxicity was more likely with greater BED radiation courses, as expected (20% vs 12% for BED <24 Gy). Pain relief was complete or very good for most sites, with <3% reporting no pain relief. Eleven sites in 9 patients required retreatment. All retreatment sites had palliation that was lasting, with a median of 22 months to last follow-up or death after repeat course (range, 0.5-106 months). There was a trend for better pain control and less risk of fracture retreatment with BED ≥24 Gy. Conclusions: Most patients had good palliation without toxicity. BED ≥24 Gy caused 8% greater risk of grade 1 toxicity and trended toward better pain control plus reduced risk of fracture retreatment.
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These NCCN Guidelines Insights highlight the important updates/changes specific to the management of Waldenström's Macroglobulinemia/Lymphoplasmacytic Lymphoma. These include the addition of regimens containing novel agents as primary and salvage therapy options, inclusion of the updated summary of response categories and criteria from the sixth international workshop on Waldenström's Macroglobulinemia, and a section on management of peripheral neuropathy in the accompanying discussion.
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Oncología Médica/tendencias , Macroglobulinemia de Waldenström/terapia , Algoritmos , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antineoplásicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Humanos , Inmunoglobulina M/inmunología , Terapia Neoadyuvante , Enfermedades del Sistema Nervioso Periférico/inmunología , Enfermedades del Sistema Nervioso Periférico/terapia , Guías de Práctica Clínica como Asunto , Pronóstico , Recurrencia , Rituximab , Terapia Recuperativa , Macroglobulinemia de Waldenström/diagnósticoRESUMEN
In 2017, the American Society for Radiation Oncology (ASTRO) board of directors prioritized radiopharmaceutical therapy (RPT) as a leading area for new therapeutic development, and the ASTRO RPT workgroup was created. Herein, the workgroup has developed a framework for RPT curriculum development upon which education leaders can build to integrate this modality into radiation oncology resident education. Through this effort, the workgroup aims to provide a guide to ensure robust training in an emerging therapeutic area within the context of existing radiation oncology training in radiation biology, medical physics, and clinical radiation oncology. The framework first determines the core RPT knowledge required to select patients, prescribe, safely administer, and manage related adverse events. Then, it defines the most important topics for preparing residents for clinical RPT planning and delivery. This framework is designed as a tool to supplement the current training that exists for radiation oncology residents. The final document was approved by the ASTRO board of directors in the fall of 2021.
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Internado y Residencia , Oncología por Radiación , Curriculum , Humanos , Oncología por Radiación/educación , Radiobiología/educación , Radiofármacos/uso terapéutico , Sociedades Médicas , Estados UnidosRESUMEN
Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.
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Neoplasias/radioterapia , Radiofármacos/uso terapéutico , Humanos , Dosificación RadioterapéuticaRESUMEN
UNLABELLED: Absorbed-dose calculations provide a scientific basis for evaluating the biologic effects associated with administered radiopharmaceuticals. In cancer therapy, radiation dosimetry supports treatment planning, dose-response analyses, predictions of therapy effectiveness, and completeness of patient medical records. In this study, we evaluated the organ radiation absorbed doses from intravenously administered (111)In- and (90)Y-ibritumomab tiuxetan. METHODS: Ten patients (6 men and 4 women) with non-Hodgkin lymphoma, cared for at 3 different medical centers, were administered the tracer (111)In-ibritumomab tiuxetan and assessed using planar scintillation camera imaging at 5 time points and CT-organ volumetrics to determine patient-specific organ biokinetics and dosimetry. Explicit attenuation correction based on the transmission scan or transmission measurements provided the fraction of (111)In-administered activity in 7 major organs, the whole body, and remainder tissues over time through complete decay. Time-activity curves were constructed, and radiation doses were calculated using MIRD methods and implementing software. RESULTS: Mean radiation absorbed doses for (111)In- and for (90)Y-ibritumomab tiuxetan administered to 10 cancer patients are reported for 24 organs and the whole body. Biologic uptake and retention data are given for 7 major source organs, remainder tissues, and the whole body. Median absorbed dose values calculated by this method were compared with previously published dosimetry for ibritumomab tiuxetan and the product package insert. CONCLUSION: In high-dose radioimmunotherapy, the importance of patient-specific dosimetry becomes obvious when the objective of treatment planning is to achieve disease cures, safely, by limiting radiation dose to any critical normal organ to its maximum tolerable value. Compared with the current package insert, we found differences in median absorbed dose by multiples of 24 in the kidneys, 1.8 in the red marrow, 0.65 in the liver, 0.077 in the intestinal wall, 0.30 in the lungs, 0.46 in the spleen, and 0.34 in the heart wall.
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Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales/farmacocinética , Carga Corporal (Radioterapia) , Radioisótopos de Indio/análisis , Radioisótopos de Indio/farmacocinética , Linfoma no Hodgkin/metabolismo , Recuento Corporal Total , Humanos , Tasa de Depuración Metabólica , Especificidad de Órganos , Dosis de Radiación , Distribución TisularRESUMEN
There is a considerable underdosage (11%-13%) of PTV due to anisotropy of a stationary source in breast balloon brachytherapy. We improved the PTV coverage by varying multiple dwell positions and weights. We assumed that the diameter of spherical balloons varied from 4.0 cm to 5.0 cm, that the PTV was a 1-cm thick spherical shell over the balloon (reduced by the small portion occupied by the catheter path), and that the number of dwell positions varied from 2 to 13 with 0.25-cm steps, oriented symmetrically with respect to the balloon center. By assuming that the perfect PTV coverage can be achieved by spherical dose distributions from an isotropic source, we developed an optimization program to minimize two objective functions defined as: (1) the number of PTV-voxels having more than 10% difference between optimized doses and spherical doses, and (2) the difference between optimized doses and spherical doses per PTV-voxel. The optimal PTV coverage occurred when applying 8-11 dwell positions with weights determined by the optimization scheme. Since the optimization yields ellipsoidal isodose distributions along the catheter, there is relative skin sparing for cases with source movement approximately tangent to the skin. We also verified the optimization in CT-based treatment planning systems. Our volumetric dose optimization for PTV coverage showed close agreement to linear or multiple-points optimization results from the literature. The optimization scheme provides a simple and practical solution applicable to the clinic.
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Braquiterapia/instrumentación , Neoplasias de la Mama/radioterapia , Radioisótopos de Iridio/administración & dosificación , Braquiterapia/métodos , Cateterismo , Femenino , Humanos , Radioisótopos de Iridio/uso terapéutico , Dosificación RadioterapéuticaRESUMEN
PURPOSE: The addition of platinum-based chemotherapy (ChRT) or cetuximab (ExRT) to concurrent radiotherapy (RT) has resulted in improved survival in Phase III studies for locoregionally advanced head and neck cancer (LAHNC). However the optimal treatment regimen has not been defined. A retrospective study was performed to compare outcomes in patients who were treated definitively with ExRT or ChRT. METHODS: Cetuximab with concurrent RT was used to treat 29 patients with LAHNC, all of whom had tumors of the oral cavity, oropharynx, or larynx. All patients were T2 to T4 and overall American Joint Committee on Cancer Stage III to IVB, with a Karnofsky Performance Status (KPS) score of 60 or greater. ChRT was used to treat 103 patients with similar characteristics. Patients were evaluated for locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). Median follow-up for patients alive at last contact was 83 months for those treated with ExRT and 53 months for those treated with ChRT. Cox proportional hazard models were used to assess independent prognostic factors. RESULTS: The LRC, DMFS, and DSS were not significantly different, with 3-year rates of 70.7%, 92.4%, and 78.6% for ExRT and 74.7%, 86.6%, and 76.5% for ChRT, respectively. The OS was significantly different between the two groups (p = 0.02), with 3-year rates of 75.9% for ExRT and 61.3% for ChRT. OS was not significant when patients who were on protocol treatments of ExRT or ChRT were compared. Also, OS was not significant when multivariate analysis was used to control for potential confounding factors. CONCLUSION: In our single-institution retrospective review of patients treated with ExRT or ChRT, no significant differences were found in LRC, DMFS, DSS, or OS.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Cetuximab , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To ascertain predictors of distant brain failure (DBF) in patients treated initially with stereotactic radiosurgery alone for newly diagnosed brain metastases. We hypothesize that these factors may be used to group patients according to risk of DBF. METHODS AND MATERIALS: We retrospectively analyzed 100 patients with newly diagnosed brain metastases treated from 2003 to 2005 at our Gamma Knife radiosurgery facility. The primary endpoint was DBF. Potential predictors included number of metastases, tumor volume, histologic characteristics, extracranial disease, and use of temozolomide. RESULTS: One-year actuarial risk of DBF was 61% for all patients. Significant predictors of DBF included more than three metastases (hazard ratio, 3.30; p = 0.004), stable or poorly controlled extracranial disease (hazard ratio, 2.16; p = 0.04), and melanoma histologic characteristics (hazard ratio, 2.14; p = 0.02). These were confirmed in multivariate analysis. Those with three or fewer metastases, no extracranial disease, and nonmelanoma histologic characteristics (N = 18) had a median time to DBF of 89 weeks vs. 33 weeks for all others. One-year actuarial freedom from DBF for this group was 83% vs. 26% for all others. CONCLUSIONS: Independent significant predictors of DBF in our series included number of metastases (more than three), present or uncontrolled extracranial disease, and melanoma histologic characteristics. These factors were combined to identify a lower risk subgroup with significantly longer time to DBF. These patients may be candidates for initial localized treatment, reserving whole-brain radiation therapy for salvage. Patients in the higher risk group may be candidates for initial whole-brain radiation therapy or should be considered for clinical trials.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Femenino , Humanos , Neoplasias Pulmonares , Masculino , Melanoma/tratamiento farmacológico , Melanoma/secundario , Melanoma/cirugía , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , TemozolomidaRESUMEN
UNLABELLED: Accurate marrow dosimetry for radionuclide therapy based on imaging methods has been challenging because of a variety of factors. One of the uncertainties in image quantification of lumbar vertebrae is correction for radioactivity in large blood vessels anterior to the vertebrae. We developed a method to correct for background radioactivity contributed from blood in large vessels and tested it in a pilot study. METHODS: CT images of 26 patients receiving (111)In- or (131)I-labeled conjugates were used to measure the inside diameters of the aorta and inferior vena cava (IVC) at the top of L2 and the bottom of L4 and to measure the length of this vessel segment. The volume was calculated for this vessel segment, and then the radioactivity in that volume at each imaging time was determined using a time-variant blood radioactivity concentration as established by serial blood samples. This vessel segment typically overlapped with lumbar vertebrae in anterior and posterior whole-body images. The contribution of this background radioactivity to the cumulated activity of the lumbar spine region of interest (ROI) from serial gamma-camera images was determined, taking into account differences in attenuation between vessel segments and lumbar vertebrae. RESULTS: The total blood volumes varied from 25 to 94 mL, with a mean of 51 mL. This mean is 76% of the mean marrow volume of 3 lumbar vertebrae measured in some of these patients. Thirteen of the 14 patients evaluated for aortic position had the aortic segment completely within the L2-L4 ROI. For the IVC, a mean of 72% was in the L2-L4 ROI. Adjusting for radioactivity in major blood vessels that were in the ROI led to lower marrow dose estimates. CONCLUSION: To improve the accuracy of lumbar spine imaging-based marrow dosimetry, one can adjust radioactivity in the large vessels by methods that measure the volume, position, and depth of vessels in the ROI.
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Artefactos , Médula Ósea/diagnóstico por imagen , Aumento de la Imagen/métodos , Vértebras Lumbares/irrigación sanguínea , Vértebras Lumbares/diagnóstico por imagen , Radiometría/métodos , Angiografía por Radionúclidos/métodos , Algoritmos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Proyectos Piloto , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: Renal toxicity associated with small-molecule radionuclide therapy has been shown to be dose-limiting for many clinical studies. Strategies for maximizing dose to the target tissues while sparing normal critical organs based on absorbed dose and biologic response parameters are commonly used in external-beam therapy. However, radiopharmaceuticals passing though the kidneys result in a differential dose rate to suborgan elements, presenting a significant challenge in assessing an accurate dose-response relationship that is predictive of toxicity in future patients. We have modeled the multiregional internal dosimetry of the kidneys combined with the biologic response parameters based on experience with brachytherapy and external-beam radiation therapy to provide an approach for predicting radiation toxicity to the kidneys. METHODS: The multiregion kidney dosimetry model of MIRD pamphlet no. 19 has been used to calculate absorbed dose to regional structures based on preclinical and clinical data. Using the linear quadratic model for radiobiologic response, we computed regionally based surviving fractions for the kidney cortex and medulla in terms of their concentration ratios for several examples of radiopharmaceutical uptake and clearance. We used past experience to illustrate the relationship between absorbed dose and calculated biologically effective dose (BED) with radionuclide-induced nephrotoxicity. RESULTS: Parametric analysis for the examples showed that high dose rates associated with regions of high activity concentration resulted in the greatest decrease in tissue survival. Higher dose rates from short-lived radionuclides or increased localization of radiopharmaceuticals in radiosensitive kidney subregions can potentially lead to greater whole-organ toxicity. This finding is consistent with reports of kidney toxicity associated with early peptide receptor radionuclide therapy and (166)Ho-phosphonate clinical investigations. CONCLUSION: Radionuclide therapy dose-response data, when expressed in terms of biologically effective dose, have been found to be consistent with external-beam experience for predicting kidney toxicity. Model predictions using both the multiregion kidney and linear quadratic models may serve to guide the investigator in planning and optimizing future clinical trials of radionuclide therapy.
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Enfermedades Renales/terapia , Riñón/efectos de la radiación , Modelos Biológicos , Dosis de Radiación , Radiometría/métodos , Radioterapia/métodos , Animales , Relación Dosis-Respuesta en la Radiación , Riñón/metabolismo , Tasa de Depuración Metabólica , Radiofármacos/metabolismo , Radiofármacos/farmacocinética , Radiofármacos/uso terapéutico , Radioterapia/efectos adversos , RatasRESUMEN
The development of radionuclide therapies during the past few decades provides a growing body of data on radiobiologic effects, including normal tissue toxicities and antitumor efficacy. Information on normal tissue toxicity from radionuclides is more limited than that from external beam radiation and appears to be more variable. Much of the increased variability is attributed to heterogeneous distribution, which complicates the potential for whole-organ toxicity, and the differences in dosimetry methodology. Although new tools are becoming available, quantitation of heterogeneous dose for radionuclides is usually less precise than dosimetry that is used in external beam radiation practice. The correlation between reported dose estimates and toxicity has improved during the past 2 decades, partly as the result of increased accuracy and standardization of dosimetry techniques and to adjustment for biologic effects. This review provides an updated compendium of dose-response relationships and consideration of dosimetry as well as radiobiologic factors that influence the reported results. Data presented are mainly derived from studies involving deliver of radiation to adults with malignancies, with most experience from radionuclides that predominantly emit beta radiation.
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Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Protección Radiológica/métodos , Radioisótopos/efectos adversos , Radioisótopos/uso terapéutico , Radioterapia/efectos adversos , Medición de Riesgo/métodos , Humanos , Factores de RiesgoRESUMEN
Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT/CT and PET/CT scanners.
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Neoplasias/terapia , Oncología por Radiación/métodos , Radioinmunoterapia/métodos , Médula Ósea/metabolismo , Médula Ósea/efectos de la radiación , Cámaras gamma , Humanos , Radioisótopos de Yodo/uso terapéutico , Oncología Médica/métodos , Neoplasias/diagnóstico por imagen , Fantasmas de Imagen , Tomografía de Emisión de Positrones/métodos , Radioisótopos/uso terapéutico , Dosificación Radioterapéutica , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X/métodos , Radioisótopos de Itrio/uso terapéuticoRESUMEN
Due to the generally slow and incomplete transit of i.p. infused agents into the circulation, treating disease confined to the peritoneal cavity with chemotherapy, biologics, and/or radionuclides provides a pharmacologic advantage. A higher i.p. concentration can be achieved than could be tolerated by systemic administration. An advantage of i.p. versus i.v. administration for localization of radiolabeled antibodies to small peritoneal surface disease has been shown in animal model and human biopsy studies (1, 2). A recent phase III Gynecologic Oncology Group chemotherapy trial has confirmed a survival advantage for i.p. delivery among women undergoing initial therapy for advanced ovarian cancer (3). Although the therapy was more difficult to tolerate such that 60% of patients randomized to the i.p. arm did not complete the entire regimen, there was a 16-month survival advantage. I.p. radionuclide therapy has been used in treatment of ovarian cancer for more than three decades, but side effects have been problematic in non-tumor-targeted 32P therapy (4). Efforts to improve specificity have used a number of antigens expressed on ovarian cancer cells as targets for selective delivery of radionuclide-conjugates. Mouse models and cell culture have been prominent for preclinical study of agents and strategies in the development of i.p. targeted radionuclide therapy for ovarian cancer. Animal studies, which have directed clinical trials, have shown clear improvement in survival with various modifications including combination chemotherapy, pretargeting, and combination of antibodies over simply delivery of a radiolabeled antibody via i.p. route.
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Anticuerpos Antineoplásicos/uso terapéutico , Antígenos de Neoplasias/inmunología , Ensayos Clínicos como Asunto , Neoplasias Ováricas/terapia , Neoplasias Peritoneales/terapia , Radioinmunoterapia , Radioisótopos/uso terapéutico , Animales , Anticuerpos Antineoplásicos/inmunología , Modelos Animales de Enfermedad , Vías de Administración de Medicamentos , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Neoplasias Peritoneales/inmunología , Neoplasias Peritoneales/secundario , Radioisótopos/farmacocinéticaRESUMEN
PURPOSE: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. METHODS: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome. RESULTS: Six dose levels (7.4, 9.6, 12.6, 16.3, 21.1, 27.4 MBq/m) were well tolerated with early possibly agent-related adverse events being mild, transient, and not dose dependent. These included asymptomatic, abnormal laboratory values. No late renal, liver, cardiac, or other toxicity was noted up to 1 year. There were no clinical signs or symptoms of an immune response to Pb-TCMC-trastuzumab, and assays to detect an immune response to this conjugate were negative for all tested. Tumor marker studies in ovarian cancer patients showed a trend of decreasing Cancer antigen 72-4 (CA 72-4) aka tumor-associated glycoprotein 72 (TAG-72) and tumor growth with increasing administered radioactivity. Other tumor markers, including carbohydrate antigen (CA125), human epididymis protein 4 (HE-4), serum amyloid A (SAA), mesothelin, interleukin-6 (IL-6), and carcinoembryonic antigen (CEA) did not correlate with imaging outcome. CONCLUSIONS: IP Pb-TCMC-trastuzumab up to 27 MBq/m seems safe for patients with peritoneal carcinomatosis who have failed standard therapies. Serum TAG-72 levels better correlated to imaging changes in ovarian cancer patients than the more common tumor marker, CA125.
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Isotiocianatos/química , Radioisótopos de Plomo/uso terapéutico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/mortalidad , Neoplasias Peritoneales/mortalidad , Radioinmunoterapia/mortalidad , Trastuzumab/uso terapéutico , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Evaluación de Resultado en la Atención de Salud , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
There is no data on safety and efficacy of a second course of ibritumomab tiuxetan. In this work, data on patients with B-cell NHL who were treated with two courses of ibritumomab tiuxetan were analyzed. Eighteen such patients were analyzed (age: 58 years, 48 - 91), with a median of four prior regimens (1 - 7), stem cell transplantation (n = 5), and radiation therapy (n = 6). After the first course, G3/4 neutropenia and thrombocytopenia was 35% and 41%; overall response rate (ORR) was 89%; time between courses was 16.6 months (6.0 - 42.7). After the second course, the incidence of G3/4 neutropenia and thrombocytopenia was 28% and 44%; and ORR 77%. There were no infectious or bleeding complications, secondary myelodysplastic syndromes, or leukemias. Retreatment with the ibritumomab tiuxetan regimen was well tolerated, with a safety profile similar to that of the first course. To conclude, patients who benefited from the first course of ibritumomab tiuxetan can benefit from retreatment.
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Anticuerpos Monoclonales/uso terapéutico , Linfoma de Células B/radioterapia , Radioinmunoterapia , Radioisótopos de Itrio/uso terapéutico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Agonistas Mieloablativos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante , Vidarabina/análogos & derivados , Irradiación Corporal TotalRESUMEN
Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose radioimmunotherapy with or without stem cell support are reviewed, as are radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfoma no Hodgkin/radioterapia , Radioinmunoterapia/métodos , Antígenos CD20/inmunología , Ensayos Clínicos como Asunto , Humanos , Radioisótopos de Itrio/uso terapéuticoRESUMEN
Radioimmunotherapy is an important new modality for treating patients with B-cell non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy of agents that deliver radiation directly to malignant cells by attaching the (131)I or (90)Y radionuclide to monoclonal antibodies against CD20. In clinical trials, (90)Y ibritumomab tiuxetan has produced rates of response as high as 83% in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan regimen is conveniently given in an outpatient setting over the course of 7-9 days. This article describes the logistics for initiating treatment, coordinating a multidisciplinary team, identifying eligible patients, and delivering the imaging and therapeutic doses of ibritumomab tiuxetan. The standard radiation safety procedures to protect family members and healthcare professionals involved in the care of patients treated with (90)Y ibritumomab tiuxetan are also reviewed. Treatment with the ibritumomab tiuxetan regimen involves only standard precautions needed to minimize radiation exposure to other persons.