RESUMO
153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.
Assuntos
Antineoplásicos , Neoplasias Ósseas , Doenças do Cão , Osteossarcoma , Compostos Radiofarmacêuticos , Animais , Cães , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Fluordesoxiglucose F18 , Coxeadura Animal/diagnóstico por imagem , Coxeadura Animal/tratamento farmacológico , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/veterinária , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Radioisótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Samário/efeitos adversosRESUMO
Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpression of cytochrome P450, hepatic overload, and the mammalian target of rapamycin pathway resistance. Although lanthanides have antitumor activity, their use is limited. Therefore, the current study aims to improve the effectiveness of zinc oxide nanoparticle via doping with lanthanides, such as samarium. In vitro study revealed that samarium doped with zinc oxide showed more antitumor activity than the other lanthanides, and the antitumor activity depends on the concentration of samarium in the nanocomposite. The in vivo experiment on mice bearing Ehrlich solid tumor revealed that intramuscular injection of samarium/zinc oxide downregulates the expressions of CXCR4 and PI3K/Akt/mammalian target of rapamycin pathway in respect to Ehrlich solid tumor group. Regarding the apoptotic biomarkers, samarium/zinc oxide upregulates the apoptotic biomarker; Bax accompanied with the mitotic catastrophe which was indicated by cell cycle arrest in G2 phase. Moreover, samarium:zinc oxide nanoparticles exhibited minimum toxicity which was indicated by suppressed activities of cytochrome P450 and hepatic enzymes, including alanine transaminase and aspartate transaminase. In addition, the histopathological finding, as well as immunophenotyping results, appreciated the biochemical finding. Therefore, samarium:zinc oxide might be offered a new approach to improve the effectiveness of zinc oxide nanoparticles along with lower toxic effect. Also, samarium:zinc oxide nanoparticles can be a candidate as a new antitumor compound to detect its mode of action.
Assuntos
Antineoplásicos/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Receptores CXCR4/antagonistas & inibidores , Samário/farmacologia , Óxido de Zinco/farmacologia , Animais , Regulação para Baixo , Feminino , Camundongos , Nanopartículas , Receptores CXCR4/genética , Samário/efeitos adversos , Óxido de Zinco/efeitos adversosRESUMO
Most countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with (90) Yttrium Citrate, (90) Yttrium hydroxyapatite or (153) Samarium hydroxyapatite in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3-51) received 1-3 RS (total 842) and follow-up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5-10 years for radio-induction of solid tumours. Moreover, ES is not a typically radio-induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated.
Assuntos
Hemofilia A/diagnóstico por imagem , Hidroxiapatitas/efeitos adversos , Hidroxiapatitas/uso terapêutico , Articulações/diagnóstico por imagem , Articulações/patologia , Samário/efeitos adversos , Samário/uso terapêutico , Membrana Sinovial/diagnóstico por imagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Hidroxiapatitas/farmacologia , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Cintilografia , Samário/farmacologia , Adulto Jovem , Radioisótopos de Ítrio/efeitos adversosRESUMO
INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.
Assuntos
Durapatita/química , Hemartrose/radioterapia , Articulação do Joelho/efeitos da radiação , Radioisótopos/química , Samário/química , Radioisótopos de Ítrio/química , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Medição de Risco , Samário/efeitos adversos , Samário/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
UNLABELLED: The radiation exposure to bystanders from 89SrCl2, 186Re-HEDP and 153Sm-EDTMP, is generally thought to be caused by "bremsstrahlung" and gamma-radiation, with negligible contribution from beta-radiation. The latter assumption may be erroneous. The aim of this prospective study was the investigation of radiation safety after treatment with these radiopharmaceuticals. The radiation field around treated patients was characterized and the magnitude estimated. PATIENTS, METHODS: 33 patients (30 prostate carcinoma, 3 breast carcinoma) were treated with 150 MBq 89SrCl2 (9 patients), 1295 MBq 186Re-HEDP (12 patients) or 37 MBq/kg 153Sm-EDTMP (12 patients). External exposure rates at 30 cm from the patient were measured at times 0 to 72 h post-injection. To evaluate the respective contribution of Bremsstrahlung, beta- and gamma-radiation, a calibrated survey meter was used, equipped with a shutter. For each patient, the measured exposure rate-versus-time data were fit to a curve and the curve integrated (area under the curve) to estimate the total exposure. RESULTS: For 29/33 patients the total ambient equivalent doses (mean+/-1 standard deviation [SD]) based on the integral of the fitted curve were 2.1+/-1.2 mSv for 89SrCl2, 3.3+/-0.6 mSv for 186Re-HEDP and 2.8+/-0.6 mSv for 153Sm-EDTMP. Beta-radiation contributes significantly to these doses (>99% for 89SrCl2, 87% for 186Re-HEDP and 27% for 153Sm-EDTMP). The effective doses (at 30 cm) are <0.1 mSv for 89SrCl2, 0.3 mSv for 186Re-HEDP and 1.6 mSv for 153Sm-EDTMP. CONCLUSION: Patients treated with 89SrCl2, 186Re-HEDP or 153Sm-EDTMP emit a spectrum of radiation, including non-negligible beta-radiation. With specific instructions effective doses to bystanders are acceptable.
Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Osso e Ossos/efeitos da radiação , Neoplasias da Mama/radioterapia , Metástase Neoplásica/radioterapia , Compostos Organometálicos/efeitos adversos , Compostos Organofosforados/efeitos adversos , Neoplasias da Próstata/radioterapia , Lesões por Radiação/prevenção & controle , Radioisótopos/efeitos adversos , Rênio/efeitos adversos , Segurança , Radioisótopos de Estrôncio/efeitos adversos , Estrôncio/efeitos adversos , Adulto , Idoso , Ácido Etidrônico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Samário/efeitos adversosRESUMO
OBJECTIVE: To investigate possible adverse effects of orthodontic magnets on the oral mucosa. METHODS: Twenty orthodontic patients, between 14 and 20 years of age, were used. All patients consented to participate in the trial, which ran for six months. Following extraction of the first premolars, samarium-cobalt (SmCo5) orthodontic magnets were used to move the upper right canines into the extraction spaces. The contralateral canines were retracted with elastomeric chain. The orthodontic appliance consisted of direct-bonded standard edgewise fibreglass brackets and molar tubes, and teflon-coated preformed archwires. At regular scheduled visits the following were recorded: the condition of the protective magnet coating; weight loss by the magnets; levels of nickel, iron and chromium ions in unstimulated saliva; viability of recovered oral mucosa cells with trypan blue. DNA fragmentation of the oral mucosa cells was analysed at the start of the trial, after one week, one month, three months and six months with the single cell gel electrophoresis assay (Comet assay). The elemental compositions of five magnets were assessed with energy dispersive X-ray microanalysis. RESULTS: By the third month the magnets had lost their protective resin coats. At six months the magnets had lost 3 per cent of their initial weights. Significant weight loss and raised saliva levels of nickel, iron and chromium ions occurred from the first week. The number of oral mucosa cells with DNA fragmentation increased steadily on both sides of the mouth from the first week. More DNA fragmented cells occurred on the Magnet side than on the Non-magnet side. The trial was discontinued when half of the subjects showed DNA damaged mucosal cells. CONCLUSIONS: Because the protective coating failed after a few weeks, orthodontic magnets are unsuitable for long-term intra-oral use. It is uncertain if the greater cell damage on the Magnet side was due to the corrosion products, proximity to the static magnetic field or both factors.
Assuntos
Materiais Revestidos Biocompatíveis/efeitos adversos , Fragmentação do DNA , Magnetismo/instrumentação , Mucosa Bucal/efeitos dos fármacos , Aparelhos Ortodônticos/efeitos adversos , Fechamento de Espaço Ortodôntico/instrumentação , Adolescente , Adulto , Cromo/análise , Cobalto/efeitos adversos , Ensaio Cometa , Corrosão , Resinas Epóxi , Feminino , Humanos , Ferro/análise , Magnetismo/efeitos adversos , Masculino , Mucosa Bucal/citologia , Níquel/análise , Fechamento de Espaço Ortodôntico/efeitos adversos , Saliva/química , Samário/efeitos adversosRESUMO
PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of (153)Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer. PATIENTS AND METHODS: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of (153)Sm-EDTMP. RESULTS: Thirty patients were treated with (153)Sm-EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of (153)Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after (153)Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after (153)Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 x 10(6) CD34(+)/kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status. CONCLUSION: (153)Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi (153)Sm-EDTMP/kg requires PBPC grafts with more than 2 x 10(6) CD34(+)/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.
Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Osteossarcoma/radioterapia , Cuidados Paliativos/métodos , Radioisótopos/uso terapêutico , Samário/uso terapêutico , Adolescente , Adulto , Criança , Relação Dose-Resposta a Droga , Doenças Hematológicas/etiologia , Doenças Hematológicas/terapia , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Compostos Organofosforados/efeitos adversos , Osteossarcoma/secundário , Radioisótopos/efeitos adversos , Samário/efeitos adversos , Distribuição TecidualRESUMO
Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose-limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans.
Assuntos
Neoplasias Ósseas/secundário , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Radioisótopos/uso terapêutico , Samário/uso terapêutico , Neoplasias Ósseas/radioterapia , Relação Dose-Resposta à Radiação , Hematopoese/efeitos dos fármacos , Humanos , Compostos Organometálicos/farmacocinética , Compostos Organofosforados/farmacocinética , Dor/radioterapia , Radioisótopos/efeitos adversos , Radioisótopos/farmacocinética , Dosagem Radioterapêutica , Samário/efeitos adversos , Samário/farmacocinéticaRESUMO
We report a case of early-onset acute Guillain-Barre syndrome associated with reactivation of Epstein-Barr virus (EBV) infection after nonmyeloablative stem cell transplantation (NST). Reactivation of EBV infection preceded disease onset, and the virus load increased concomitantly with disease progression (doubling time, 2.7 days). This case raises concern about the expanding scope of manifestations associated with reactivation of EBV infection after NST.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Síndrome de Guillain-Barré/etiologia , Transplante de Células-Tronco/efeitos adversos , Ativação Viral/efeitos dos fármacos , Soro Antilinfocitário/efeitos adversos , Bussulfano/efeitos adversos , Infecções por Vírus Epstein-Barr/virologia , Síndrome de Guillain-Barré/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Samário/efeitos adversos , Vidarabina/efeitos adversos , Vidarabina/análogos & derivadosRESUMO
Samarium-153-ethylenediaminetetramethylene phosphoric acid (EDTMP), a bone-seeking radiopharmaceutical, was given to prostate cancer patients in a dose escalation protocol for pain palliation to determine the maximally tolerated dose. Fifty-two patients with hormone refractory prostate cancer with bony metastases were treated with doses beginning at 0.5 mCi/kg (18.5 MBq/kg), escalating in 0.5-mCi (18.5 MBq) increments to 3.0 mCi/kg (111 MBq/kg). Pain response after treatment was assessed as well as hematologic and serum chemistry parameters. Pain palliation with a mean duration of 2.6 mo was present in 74% of the patients. Toxicity was exclusively hematologic at the highest dose levels. No infectious or bleeding complications occurred, with 45 of the 52 (86%) patients demonstrating complete hematologic recovery. Patients receiving higher doses had significantly greater reductions in serum prostate specific antigen and serum prostatic acid phosphatase levels. The patients receiving greater doses also showed a trend toward improved survival.
Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Neoplasias da Próstata/patologia , Radioisótopos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Hormônios/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Compostos Organofosforados/efeitos adversos , Medição da Dor , Neoplasias da Próstata/tratamento farmacológico , Radioisótopos/efeitos adversos , Cintilografia , Dosagem Radioterapêutica , Samário/efeitos adversos , Samário/uso terapêuticoRESUMO
UNLABELLED: Palliation of bone pain in patients with cancer metastatic to bone is being evaluated in several cancer centers by the administration of the bone-seeking phosphonate ethylenediaminetetramethylenephosphonic acid (EDTMP) chelated with the beta particle-emitting radionuclide 153Sm. METHODS: In this study, 153Sm-EDTMP was intravenously injected into 19 patients over a 1-min period. Patients received up to four injections of 18.5 MBq (0.5 mCi) or 37 MBq (1.0 mCi) per kilogram of body weight. Skeletal retention was calculated from urinary excretion. RESULTS: No uptake of 153Sm-EDTMP in nonskeletal tissues was observed in whole-body gamma camera images. The mean skeletal uptake for all patients was 54% +/- 16% of the injected dose (%ID). This resulted in the bone marrow receiving 89 cGy/GBq +/- 27 cGy/GBq (3.28 cGy/mCi +/- 0.99 cGy/mCi), with calculated marrow doses ranging from 27 cGy to 338 cGy. For each patient, the estimated radiation absorbed dose to the marrow was correlated to the percent decrease in platelet number, ranging from 7.4% to 78.9%. CONCLUSION: Since the deviation of uptake between the four injections for a given patient (7.6% ID) was less than the deviation for all patients (16% ID), the initial dose may be used to estimate the skeletal uptake for the remaining doses. These radiation dose estimates permit patients at risk to be identified prior to reaching myelotoxicity and develop dose-response models. Thirteen patients (68%) reported significant pain relief from this radionuclide therapy. Bone pain appears to be alleviated by 153Sm-EDTMP with limited red marrow doses and no toxic effects in other organs.
Assuntos
Neoplasias Ósseas/secundário , Compostos Organofosforados/uso terapêutico , Dor/radioterapia , Radioisótopos/uso terapêutico , Samário/uso terapêutico , Medula Óssea/efeitos dos fármacos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/fisiopatologia , Osso e Ossos/diagnóstico por imagem , Quelantes/uso terapêutico , Humanos , Compostos Organofosforados/efeitos adversos , Dor/etiologia , Cuidados Paliativos , Radioisótopos/efeitos adversos , Cintilografia , Dosagem Radioterapêutica , Samário/efeitos adversosRESUMO
INTRODUCTION: The optimal dose of samarium-153-EDTMP (153Sm-EDTMP) for effective palliation of painful metastases to bone is under investigation. It is not known whether increased doses of 153Sm EDTMP will lead to better and longer pain and tumour control and survival. Multiple dose efficacy and toxicity is of importance as most Patients will require prolonged support for pain. METHODS: Twenty-eight (28) patients were treated with 0.75 mCi/kg, 35 patients with 1.5 mCi/kg and 19 patients with 3 mCi/kg in three sequential Phase I-II trials. Multiple doses were given to patients on the 0.75 mCi/kg and 1.5 mCi/kg dose levels. RESULTS: At all dose levels adequate pain control was achieved in 78-95% of patients. The duration of pain control was 40-56 days with the best results in the 1.5 mCi/kg group (56 days). There is no evidence that increasing dose leads to better and longer pain control, tumour response and survival, but toxicity is increased. Multiple doses can be given with acceptable toxicity and pain control, however, only 38% of patients will qualify for multiple treatments. CONCLUSION: 153Sm-EDTMP provides adequate and safe palliation but multiple doses can only be given in 38% of patients. There is not a clear dose-response relationship. The length of pain control is satisfactory but not ideal and hospitalisation for 4 days every 6-8 weeks is a disadvantage. Further research is required to combine 153Sm-EDTMP with cytostatics and to administer it on an out patient basis.
Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Compostos Organometálicos/administração & dosagem , Compostos Organofosforados/administração & dosagem , Cuidados Paliativos , Radioisótopos/administração & dosagem , Samário/administração & dosagem , Relação Dose-Resposta à Radiação , Humanos , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Compostos Organofosforados/efeitos adversos , Dor/etiologia , Manejo da Dor , Radioisótopos/efeitos adversos , Dosagem Radioterapêutica , Samário/efeitos adversosRESUMO
The cochlear implant is an electronic auditory prosthesis gaining widespread acceptance as a means of restoring partial hearing to the totally deaf. A number of engineering and biological hurdles remain toward the improvement of existing implantable systems and development of multichannel systems. One hurdle concerns reliable transcutaneous coupling of the external electric signal to the implanted device. To date this has been accomplished by inductive means through coils which were mechanically held in place. The incorporation of small, permanent, rare-earth (SmCo5) magnets with the coil assemblies has eliminated the unreliable mechanical supporting devices. Magnetic attachment was simulated in dogs to examine for biological compatibility. Electron micrographs indicated normal subcellular structures in tissue exposed for 10 weeks. Five patients were implanted with magnet-modified coil assemblies and tested for the proper alignment and support of the external coil assembly, as well as efficiency of inductive coupling. Electromagnetic coupling was not interfered with and mechanical support was adequate. We conclude that rare-earth magnets provide an effective means for supporting and positioning in place medical devices, such as the cochlear implant.
Assuntos
Cobalto , Implantes Cocleares/instrumentação , Fenômenos Eletromagnéticos , Samário , Animais , Materiais Biocompatíveis , Cobalto/efeitos adversos , Cães , Humanos , Microscopia Eletrônica , Samário/efeitos adversos , Pele/ultraestruturaRESUMO
Metabolic radiotherapy is a new therapy for management of bone pain in patients with bone metastatic prostate carcinoma. Strontium-89 and Samarium-153 concentrate in bone metastases and radiate them. A pain decrease is obtained in 60-70% of cases. Side effects are a significant hematological depression without great clinical consequences if good therapeutic indications are respected. Our multidisciplinary experience of these radionuclides in 54 performed treatments shows a rate of good responders of 66% with a rate of excellent results (total decrease of pain) in 47%. The therapeutic effectiveness is correlated with pain intensity measured by Visual Analogic Scale (VAS) and equivalent dose of morphine. Radionuclide therapy should be applied to patients as early as possible after establishment of bone metastases.
Assuntos
Adenocarcinoma/radioterapia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias da Próstata/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Adenocarcinoma/epidemiologia , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/metabolismo , Ensaios Clínicos como Assunto , Método Duplo-Cego , Previsões , França/epidemiologia , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/efeitos adversos , Compostos Organofosforados/farmacocinética , Compostos Organofosforados/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Dor/radioterapia , Cuidados Paliativos , Radioisótopos de Fósforo/efeitos adversos , Radioisótopos de Fósforo/farmacocinética , Radioisótopos de Fósforo/uso terapêutico , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Radioisótopos/efeitos adversos , Radioisótopos/farmacocinética , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Rênio/efeitos adversos , Rênio/farmacocinética , Rênio/uso terapêutico , Samário/efeitos adversos , Samário/farmacocinética , Samário/uso terapêutico , Estrôncio/efeitos adversos , Estrôncio/farmacocinética , Estrôncio/uso terapêutico , Radioisótopos de Estrôncio/efeitos adversos , Radioisótopos de Estrôncio/farmacocinética , Radioisótopos de Estrôncio/uso terapêutico , Resultado do TratamentoRESUMO
AIM: The breast cancer and the prostate cancer are considered as the most frequently occurred metastatic tumors in bones. The bone pain appears in majority of patients with metastases. One possibility how to reduce or to remove this pain is the administration of the radiotherapy to the place of metastases. The present medicine disposes of two ways how to administer radiotherapy in the place of metastases: externally irradiation (loco-regional or half-body) or intravenous administration of bone-seeking therapeutic radiopharmaceuticals. MATERIAL AND METHOD: We introduced intravenous administration of 153Samarium-EDTMP in 57 patients (30 prostate cancer, 23 breast cancer, 4 renal cell carcinoma). Mean applied activity was 40 MBq per kg of patient's body weight. RESULTS: After 153Sm-EDTMP administration we observed pain relief of various degree in 75% of patients for three months. 1 and 3 months after 153Samarium-EDTMP administration the following haematologic parameters changes were seen: a) 7% reduction in red cell count in one month after administration, 15% reduction after three months. b) 43% reduction in leukocyte count in one month after administration, 24% reduction after three months. c) 50% reduction in platelet count in one month after administration, 23% reduction after three months. In all three haematological profiles (red cells, leukocytes, platelets) we detected reduction of values after treatment with 153Samarium-EDTMP. This reduction culminates one month after administration and in three months leukocytes and platelets count was getting better. CONCLUSION: Myelosuppression was mild and temporary. No patients had grade 4 hematological toxicity and only three patients (5%) had grade 3 hematological toxicity (National Cancer Institute Common Toxicity Criteria).
Assuntos
Medula Óssea/efeitos dos fármacos , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Dor Intratável/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Samário/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Infusões Intravenosas , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/efeitos adversos , Compostos Organofosforados/efeitos adversos , Dor Intratável/etiologia , Cuidados Paliativos , Pancitopenia/etiologia , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/efeitos adversos , Samário/efeitos adversosRESUMO
OBJECTIVES: The aim of the present study was to investigate the effectiveness of Samarium(153)-particulate hydroxyapatite radiation synovectomy in rheumatoid arthritis patients with chronic knee synovitis. METHODS: Fifty-eight rheumatoid arthritis patients (60 knees) with chronic knee synovitis participated in a controlled double-blinded trial. Patients were randomized to receive either an intra-articular injection with 40 mg triamcinolone hexacetonide alone (TH group) or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium(153)-particulate hydroxyapatite (Sm/TH group). Blinded examination at baseline (T0) and at 1 (T1), 4 (T4), 12 (T12), 32 (T32), and 48 (T48) weeks post-intervention were performed on all patients and included a visual analog scale for joint pain and swelling as well as data on morning stiffness, flexion, extension, knee circumference, Likert scale of improvement, percentage of improvement, SF-36 generic quality of life questionnaire, Stanford Health Assessment Questionnaire (HAQ), Lequesne index, use of non-steroidal anti-inflammatory drugs or oral corticosteroids, events and adverse effects, calls to the physician, and hospital visits. RESULTS: The sample was homogeneous at baseline, and there were no withdrawals. Improvement was observed in both groups in relation to T0, but no statistically significant differences between groups were observed regarding all variables at the time points studied. The Sm/TH group exhibited more adverse effects at T1 (p<0.05), but these were mild and transitory. No severe adverse effects were reported during follow-up. CONCLUSION: Intra-articular injection of Samarium(153)-particulate hydroxyapatite (15 mCi) with 40 mg of triamcinolone hexacetonide is not superior to triamcinolone hexacetonide alone for the treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of follow-up.
Assuntos
Anti-Inflamatórios/efeitos adversos , Artrite Reumatoide/radioterapia , Hidroxiapatitas/efeitos adversos , Articulação do Joelho , Radioisótopos/efeitos adversos , Samário/efeitos adversos , Sinovite/radioterapia , Anti-Inflamatórios/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Doença Crônica , Combinação de Medicamentos , Métodos Epidemiológicos , Feminino , Humanos , Hidroxiapatitas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Radioisótopos/uso terapêutico , Samário/administração & dosagem , Sinovite/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/efeitos adversos , Triancinolona Acetonida/análogos & derivadosRESUMO
PURPOSE: (153)Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. METHODS: Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg (153)Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before (153)Sm-EDTMP treatment. Urine was collected 48 h after injection of (153)Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of (153)Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. RESULTS: The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 +/- 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 +/- 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with (153)Sm-EDTMP. CONCLUSION: Zoledronic acid treatment does not influence (153)Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Samário/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/radioterapia , Terapia Combinada , Difosfonatos/efeitos adversos , Humanos , Imidazóis/efeitos adversos , Injeções Intravenosas , Masculino , Taxa de Depuração Metabólica , Metástase Neoplásica , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/farmacocinética , Compostos Organofosforados/administração & dosagem , Compostos Organofosforados/efeitos adversos , Compostos Organofosforados/farmacocinética , Neoplasias da Próstata/patologia , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Radioisótopos/farmacocinética , Samário/administração & dosagem , Samário/efeitos adversos , Samário/farmacocinética , Ácido ZoledrônicoRESUMO
OBJECTIVE: This study was designed to evaluate vascular morphological and morphometric changes induced by brachytherapy with samarium-153 (Sm-153) at high doses in hypercholesterolemic rabbits. METHODS: Forty-three New Zealand White hypercholesterolemic rabbits were analyzed, and the total of 86 iliac arteries underwent balloon angioplasty injury. The rabbits were divided into three different groups: two irradiation groups (IG) assigned to 15 Gy (n=14) and 60 Gy (n=36) irradiation doses, respectively, and a control group (n = 36). Histomorphometric and qualitative histological analyses were performed for tissue evaluation. RESULTS: Significant reductions were found in neointimal proliferation (NIP) (p< 0.0001), media area (MA) (p<0.0001) and percent stenosis (p<0.0001) in the 15-Gy IG, compared to the other groups. The 60-Gy IG had the higher rate of NIP, increase in media and vessel areas (VA) and percent stenosis. The 60-Gy IG also showed the greatest number of xanthomatous cells (60-Gy IG: 86.11% and 15-Gy IG: 14.29%, p<0.0001) and the highest amount of hyaline amorphous tissue (60-Gy IG:58.33% and 15-Gy IG:0%, p=0.0001) and vascular proliferation (60-Gy IG:30.56% and 15-Gy IG:0%, p=0.0221). No statistically significant differences were found among groups concerning other tissue analyses. CONCLUSION: The high-dose irradiation of 60 Gy resulted in intense cell proliferation considered vascular radiolesion, unlike the 15-Gy dose, which was associated with an excellent inhibition of neointimal proliferation.
Assuntos
Aorta Abdominal/efeitos da radiação , Braquiterapia/efeitos adversos , Hipercolesterolemia , Artéria Ilíaca/efeitos da radiação , Radioisótopos/efeitos adversos , Samário/efeitos adversos , Animais , Aorta Abdominal/patologia , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/patologia , Artéria Ilíaca/patologia , Coelhos , Radiografia , Índice de Gravidade de Doença , Túnica Íntima/patologia , Túnica Íntima/efeitos da radiação , Túnica Média/patologia , Túnica Média/efeitos da radiaçãoRESUMO
Samarium-153 lexidronam (153Sm-EDTMP) is FDA approved for painful osteoblastic bone metastases that image on bone scan. 153Sm-EDTMP decay has a therapeutic beta-emission and a gamma-photon for bone scan imaging. Monitoring of osteosarcoma radiation treatment effectiveness was performed with bone, CT, MRI and PET/CT fusion imaging. Bone scan and PET/CT improved in 5 out of 9 and 16 out of 18 osteosarcoma sites, respectively. 153Sm-EDTMP targets multiple sites of disease, with a single administration. Side effects of 153Sm-EDTMP (0.5-2.5 mCi/kg) have been minimal and include transient thrombocytopenia and neutropenia. 153Sm-EDTMP can be combined with radiation therapy, bisphosphonates and/or chemotherapy to synergistically improve palliation. This article reviews the rationale, indications and monitoring of standard-dose samarium and investigational high-dose 153Sm-EDTMP treatment of cancer involving bone.