RESUMO
Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled, double-blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG-induced PN. Methods. Patients with ovarian cancer (OC) or castration-resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG (16 mg/m(2) intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of PN within six or fewer cycles in both treatment groups. Results. Overall, 150 patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm. No significant difference in overall PN incidence was observed between treatment arms. The incidence of grade ≥3 PN was significantly lower in the ALC arm in OC patients. Median duration of neuropathy was similar between treatment arms. The best overall response (according to the modified Response Evaluation Criteria in Solid Tumors), response according to tumor markers, time-to-event variables, and discontinuations because of adverse events (AEs) were comparable between treatment arms. Conclusion. Administration of ALC with SAG did not result in a significant difference in overall PN incidence compared with a PBO. OC patients in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN compared with OC patients in the SAG/PBO arm.
Assuntos
Acetilcarnitina/uso terapêutico , Benzotiazóis/efeitos adversos , Epotilonas/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Acetilcarnitina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Benzotiazóis/uso terapêutico , Método Duplo-Cego , Epotilonas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
Lung perfusion scintigraphy (LPS) with technetium-99m-labeled macro-aggregates of albumin (Tc-99m-MAA) is well established in the diagnostic of pulmonary embolism (PE). In the last decade, it was shown that single-photon emission computer tomography (SPECT) acquisition of LPS overcame static scintigraphy. Furthermore, there are rare indications for LPS, such as preoperative quantification of regional lung function prior to lung resection or transplantation, optimization of lung cancer radiation therapy, quantification of right-left shunt, planning of intra-arterial chemotherapy, and several rare indications in pediatrics. Moreover, LPS with Tc-99m-MAA is a safe method with low radiation exposure. PE can also be diagnosed by spiral computer tomography (CT), ultrasound, magnetic resonance angiography, or pulmonary angiography (PA, former gold standard). The present review considers all these methods, especially spiral CT, and compares them with LPS with respect to sensitivity and specificity and gives an overview of established and newer publications. It shows that LPS with Tc-99m-MAA represents a diagnostic method of continuing value for PE. In comparison with spiral CT and/or PA, LPS is not to be defeated as mentioned also by the most actual Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II reports. This applies in particular to chronic or recurring embolisms, whereas currently spiral CT may be of greater value for major or life-threatening embolisms. At present, LPS cannot be replaced by other methods in some applications, such as pediatrics or in the quantification of regional pulmonary function in a preoperative context or prior to radiation therapy. LPS still has a place in the diagnostics of PE and is irreplaceable in several rare indications as described earlier.
Assuntos
Pulmão/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Agregado de Albumina Marcado com Tecnécio Tc 99m/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Administração por Inalação , Humanos , Injeções Intravenosas , Marcação por Isótopo/métodosRESUMO
UNLABELLED: 131I-labeled metaiodobenzylguanidine (MIBG) is an established treatment modality for neuroendocrine tumors. Because of low tumor doses, it has a predominantly palliative character. Our approach was to investigate whether intraarterial application of 131I-MIBG has the potential to enhance tumor uptake. METHODS: Seventeen patients with primary or metastasized neuroendocrine tumors received intraarterial treatment with 131I-MIBG, and 12 of these patients also had intravenous treatment. Every patient underwent intravenous 131I-MIBG whole-body scanning before therapy. For quantification, a tumor-to-whole-body ratio was calculated from the diagnostic and 24-h posttreatment scans. RESULTS: Compared with the intravenous application, intraarterial 131I-MIBG treatment provided an up to 4-fold higher tumor uptake. Mean uptake was enhanced by 69%, but this varied widely between patients. We did not observe any immediate complications from catheterization. Carcinoid-related side effects were noted in 7 of 17 patients and were not different from those seen with intravenous application. CONCLUSION: Intraarterial treatment with 131I-MIBG is a safe alternative to intravenous application and provides a 69% higher mean tumor uptake. We propose to attempt intraarterial MIBG treatment in every patient to assess its potential benefit.
Assuntos
3-Iodobenzilguanidina/farmacologia , Antineoplásicos/farmacologia , Radioisótopos do Iodo/farmacologia , Neoplasias/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacologia , Idoso , Tumor Carcinoide/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cintilografia , Imagem Corporal TotalRESUMO
Radioembolization of tumors after selective catheterization has been proven to be an effective therapy in nuclear medicine. The goal of the study was to evaluate the (188)Re labeling and in vitro and in vivo stability of several representative non-degradable polymeric microspheres and biodegradable particles. The biodistribution after i.v. injection in Wistar rats revealed excellent in vivo stability with low uptake in the non-target tissues over 48 h for some polymeric particles and especially for biodegradable human serum albumin microspheres.
Assuntos
Embolização Terapêutica/métodos , Radioisótopos/uso terapêutico , Rênio/uso terapêutico , Animais , Microesferas , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
PURPOSE: 153Sm-lexidronam has been used for the palliation of symptoms from painful bone metastases for years, while docetaxel has recently been shown to improve the survival of patients with hormone-refractory prostate cancer (HRPC). The first clinical experience with the combination of both treatment modalities is reported. METHODS: Between 2005 and 2006, 12 patients with muliple bone metastases from HRPC were treated with a single application of 37 MBq/kg body weight 153Sm-lexidronam and 6 weekly infusions of 35 mg/m2 docetaxel. Data on survival, prostate-specific antigen (PSA) response, symptom palliation, toxicity, and scintigraphic follow-up are provided. RESULTS: Mean follow-up was 11.4 (range, 1.1-25.8) months, overall 1-year survival was 48.6%, and median survival was 11.5 months. A PSA response of >50% was documented in 50% of patients. The average pain score (visual analog scale: 1-10) was reduced from 5.1 to 1.4 (p = 0.016) with decrease of > or =2 in 58.3% of patients. The average World Health Organization medication level dropped from 1.6 to 1.1 (p = 0.5). Overall toxicity was moderate, but 1 patient died due to neutropenic sepsis. CONCLUSIONS: Our analysis demonstrates feasibility and therapeutic potential for the combination treatment and merits prospective investigation. Further studies will be planned with respect to the potentially synergistic hematologic toxicity of bone-seeking radiopharmaceuticals and chemotherapy.