RESUMEN
OBJECTIVES: Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177Lu-DOTATATE. Our program transitioned to compounded l-arginine 2.5%/l-lysine 2.5% in 0.9% NaCl after commercial approval of 177Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations. METHODS: Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities. RESULTS: Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%). CONCLUSIONS: Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.
Asunto(s)
Aminoácidos/uso terapéutico , Náusea/diagnóstico , Tumores Neuroendocrinos/terapia , Octreótido/análogos & derivados , Compuestos Organometálicos/uso terapéutico , Nutrición Parenteral/métodos , Vómitos/diagnóstico , Anciano , Anciano de 80 o más Años , Aminoácidos/administración & dosificación , Aminoácidos/efectos adversos , Arginina/administración & dosificación , Arginina/efectos adversos , Arginina/uso terapéutico , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Femenino , Humanos , Bombas de Infusión , Lisina/administración & dosificación , Lisina/efectos adversos , Lisina/uso terapéutico , Masculino , Persona de Mediana Edad , Náusea/etiología , Octreótido/administración & dosificación , Octreótido/efectos adversos , Octreótido/uso terapéutico , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/efectos adversos , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Nutrición Parenteral/efectos adversos , Radiofármacos/administración & dosificación , Radiofármacos/efectos adversos , Radiofármacos/uso terapéutico , Receptores de Péptidos/química , Estudios Retrospectivos , Vómitos/etiologíaRESUMEN
RATIONALE: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is a targeted internal radiotherapy method used to treat tumors expressing somatostatin receptors. Concomitant amino acids perfusion is systematically performed in order to inhibit the proximal tubular uptake of the radionuclide and thus prevent nephrotoxicity. PATIENT CONCERNS:: a 67-year-old woman with an intestinal neuroendocrine tumor with multiple lymphadenopathies and liver metastases. The patient displayed a carcinoid syndrome with flushes including facial erythrosis and paresthesia. During the treatment, the patient exhibited emesis and severe cramps. DIAGNOSIS: We describe incomplete proximal tubulopathy induced by an amino acid therapy with [177Lu]-DOTA0-Tyr3-octreotate, which was reversible after treatment discontinuation. This diagnosis relies on metabolic acidosis, hypophosphatemia due to renal loss, tubular proteinuria and generalized aminoaciduria. Serum creatinine remained stable during and after the procedure. INTERVENTIONS: PRRT with radiolabeled somatostatin analog ([177Lu]-DOTA0-Tyr3-octreotate). In order to prevent PRRT induced nephrotoxicity, we used a solution of 20 amino acids including 22âg/L Lysine and 16.8âg/L Arginine. Metoclopramide was successfully used to control vomiting. During the treatment and at the time of cramps, the blood sample showed hypophosphatemia at 0.3âmmol/L justifying intravenous phosphate supplementation. The cramps disappeared after this infusion. OUTCOMES: Hypophosphatemia with low TmPO4/GFR was observed as well as an increase in ß2-microglobulinuria, urinary polyclonal light chains, and amino aciduria involving all amino acids. All these disturbances disappeared the day after the treatment and there was no acute kidney injury after 5 PRRT sessions. Six months after PRRT discontinuation, the patient had neither renal failure nor proximal tubulopathy. Aminoacid induced tubulopathy involves the main ligands of the megalin receptor. It has recently been demonstrated that cilastatin is a megalin inhibitor in the proximal tubule and therefore could represent an attractive alternative to amino acids for this purpose. LESSONS: This case report is a description of a nephroprotective strategy in which partial, and transient tubulopathy is induced, in order to decrease proximal absorption of a tubulotoxic molecule. This little known strategy could be used to prevent proximal tubular injury caused by others megalin-mediated nephrotoxicity medication.
Asunto(s)
Aminoácidos/efectos adversos , Síndrome de Fanconi/inducido químicamente , Octreótido/análogos & derivados , Compuestos Organometálicos/efectos adversos , Anciano , Aminoácidos/administración & dosificación , Femenino , Humanos , Neoplasias Intestinales/radioterapia , Túbulos Renales Proximales/efectos de los fármacos , Tumores Neuroendocrinos/radioterapia , Octreótido/efectos adversos , Octreótido/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Radioisótopos/efectos adversos , Radioisótopos/uso terapéutico , Receptores de PéptidosRESUMEN
Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor-expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.
Asunto(s)
Síndrome de Gitelman/inducido químicamente , Neoplasias del Íleon/radioterapia , Tumores Neuroendocrinos/radioterapia , Octreótido/análogos & derivados , Compuestos Organometálicos/efectos adversos , Desequilibrio Hidroelectrolítico/inducido químicamente , Acidosis/inducido químicamente , Acidosis/metabolismo , Acidosis/terapia , Anciano , Calcitriol/uso terapéutico , Carbonato de Calcio/uso terapéutico , Quimioradioterapia Adyuvante , Procedimientos Quirúrgicos del Sistema Digestivo , Fluidoterapia , Síndrome de Gitelman/metabolismo , Síndrome de Gitelman/terapia , Humanos , Hipocalcemia/inducido químicamente , Hipocalcemia/metabolismo , Hipocalcemia/terapia , Hipopotasemia/inducido químicamente , Hipopotasemia/metabolismo , Hipopotasemia/terapia , Sulfato de Magnesio/uso terapéutico , Masculino , Octreótido/efectos adversos , Vitaminas/uso terapéutico , Desequilibrio Hidroelectrolítico/metabolismo , Desequilibrio Hidroelectrolítico/terapiaRESUMEN
PURPOSE: Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. METHODS: In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). RESULTS: Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. CONCLUSION: Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.
Asunto(s)
Neoplasias del Sistema Digestivo/radioterapia , Neoplasias Pulmonares/radioterapia , Tumores Neuroendocrinos/radioterapia , Octreótido/análogos & derivados , Dosis de Radiación , Radiofármacos/uso terapéutico , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Neoplasias del Sistema Digestivo/diagnóstico por imagen , Femenino , Humanos , Riñón/fisiopatología , Riñón/efectos de la radiación , Pruebas de Función Renal , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/administración & dosificación , Octreótido/efectos adversos , Octreótido/uso terapéutico , Medicina de Precisión/métodos , Radiometría , Cintigrafía , Radiofármacos/administración & dosificación , Radiofármacos/efectos adversos , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/efectos adversosAsunto(s)
Quilotórax/terapia , Fármacos Gastrointestinales/uso terapéutico , Octreótido/uso terapéutico , Nutrición Parenteral Total/métodos , Adulto , Neoplasias de los Bronquios/complicaciones , Neoplasias de los Bronquios/terapia , Quilotórax/etiología , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/terapia , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/terapia , Octreótido/administración & dosificación , Octreótido/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Sulfonylureas are used extensively for treating type-2 diabetes mellitus. Sulfonylurea poisoning can produce sustained and profound hypoglycemia refractory to IV dextrose, particularly in children and the elderly. OBJECTIVE: To review the use of octreotide, a long-acting somatostatin analog, in the treatment of sulfonylurea-induced hypoglycemia. METHODS: A computerized search of U.S. National Academy of Medicine, Embase, PubMed and Toxline databases was undertaken using the keywords "octreotide", "sulfonylurea", "poisoning", "intoxication", "overdose" and "children". Textbooks of Clinical Toxicology and Pharmacology and the articles cited in their bibliographies were also searched. Twenty-four publications (19 articles and five conference abstracts) were identified; no publication was excluded. PHARMACOLOGY OF OCTREOTIDE: Octreotide, a synthetic peptide analog of somatostatin, binds to G protein-coupled somatostatin-2 receptors in pancreatic beta-cells, resulting in decreased calcium influx and inhibition of insulin secretion. Octreotide markedly inhibited insulin secretion and decreased the number of hypoglycemic events and supplemental dextrose requirements in animal studies. In humans octreotide markedly inhibited insulin release, increased serum glucose concentration, reduced dextrose requirement, prevented recurrent hypoglycemia and was superior to IV dextrose and diazoxide after administration of sulfonylureas. EFFICACY OF OCTREOTIDE IN PEDIATRIC SULFONYLUREA POISONING: Fourteen pediatric patients were reported; 13 ingested second-generation sulfonylureas, with time to hypoglycemia of 1.5-16 hours. IV dextrose (10-25%) was administered before and after octreotide therapy. Octreotide was given after failure to correct hypoglycemia with IV dextrose in doses of 0.51-2 µg/kg IV or SC; two also required an IV octreotide infusion. Seven patients (50%) had recurrent hypoglycemia and received IV dextrose and additional octreotide. EFFICACY OF OCTREOTIDE IN ADULT SULFONYLUREA POISONING: Fifty-three patients were reported in prospective controlled (n = 22) and retrospective (n = 9) studies, case series (n = 6) and case reports. Fifty-one ingested second-generation sulfonylureas with time to hypoglycemia of 1-13 hours. All received IV dextrose (10-50%) before and after octreotide treatment. Octreotide 40-100 µg SC or IV was administered followed by additional doses in most patients; three patients also required an IV infusion. Octreotide significantly increased serum glucose concentrations, decreased dextrose requirement and recurrent hypoglycemic events compared with IV dextrose. Recurrent hypoglycemia was recorded in 22-50% of the patients treated with octreotide. THERAPEUTIC RECOMMENDATIONS: Based on the published clinical and pharmacokinetic data of sulfonylureas and octreotide, we suggest the following dose regimens: in children, octreotide 1-1.5 µg/kg IV or SC, followed by 2-3 more doses 6 hours apart. In adults, octreotide 50 µg SC or IV, followed by three 50 µg doses every 6 hours. During this treatment IV dextrose infusion should be gradually tapered off. ADVERSE EVENTS: Hypertension and apnea were recorded in one pediatric patient 30 minutes after IV octreotide; the relationship to octreotide is unclear. One adult patient with chronic renal failure treated with atenolol developed severe hyperkalemia. CONCLUSIONS: Although relatively limited, the available data suggest that octreotide should be considered first-line therapy in both pediatric and adult sulfonylurea poisoning with clinical and laboratory evidence of hypoglycemia. Maintenance doses of octreotide may be required to prevent recurrent hypoglycemia.
Asunto(s)
Hipoglucemia/tratamiento farmacológico , Octreótido/uso terapéutico , Compuestos de Sulfonilurea/envenenamiento , Animales , Humanos , Octreótido/efectos adversos , Octreótido/farmacologíaRESUMEN
OBJECTIVES: Lymphomas are the main form of haematological neoplasms, representing 55.6% of all tumours of the blood. Overall, they account for 5.3% of all malignant tumours (excluding basal and squamous cell skin cancer) in Italy with a prevalence constantly increasing at a rate of 3% per year. From a histological point of view, they represent a vast heterogeneous group of haematological diseases, their staging being based on defined cyto-morphological and anatomo-pathological criteria. Although the combined use of standard approaches can provide good response rates, recurrence is particularly frequent in patients undergoing traditional treatment, with critical and often irreversible side effects such as myelosuppression and a high frequency of opportunistic infections and sterility. Numerous epidemiological studies and preclinical data have for some time now reported the anticancer effects of molecules such as Melatonin, Retinoids, Vitamins E, D3, and C, Somatostatin and prolactin inhibitors in neoplastic diseases. There are, however, very few publications on the combined effects of these substances in vivo. METHODS: We report an observational study carried out on 55 patients affected by various forms of lymphoma, treated with the biological therapy known as the Di Bella Method (DBM). The 1, 3 and 5-year survival rates are reported, together with any signs of toxicity. RESULTS: The DBM treatment achieved partial or complete objective responses in a shorter time and in greater percentages if administered as first-line therapy. The adjuvant treatment increased survival time and improved quality of life with respect to the data reported in the literature for the same types and stages of lymphoma. CONCLUSION: Overall, the treatment was well tolerated, with minor and transient side effects. The patients were able to continue the treatment at home, carrying out their normal activities without problems.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Femenino , Hormonas/administración & dosificación , Hormonas/efectos adversos , Humanos , Masculino , Melatonina/administración & dosificación , Melatonina/efectos adversos , Persona de Mediana Edad , Octreótido/administración & dosificación , Octreótido/efectos adversos , Proyectos Piloto , Prevalencia , Retinoides/administración & dosificación , Retinoides/efectos adversos , Estudios Retrospectivos , Somatostatina/administración & dosificación , Somatostatina/efectos adversos , Análisis de Supervivencia , Vitaminas/administración & dosificación , Vitaminas/efectos adversos , Adulto JovenRESUMEN
PURPOSE: Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence. PATIENTS AND METHODS: The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology. RESULTS: Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis. CONCLUSION: Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adulto , Anciano , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Péptido C/sangre , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Persona de Mediana Edad , Octreótido/administración & dosificación , Octreótido/efectos adversos , Posmenopausia , Calidad de Vida , Tamoxifeno/administración & dosificación , Tamoxifeno/efectos adversos , Resultado del Tratamiento , Vitamina D/sangreRESUMEN
OBJECTIVE: The metabolic response to gastrointestinal cancer in patients undergoing surgery is associated with hypermetabolism and insulin resistance. The potential use of synergetic anabolic hormones in conjunction with hypocaloric parenteral nutrition (HPN) has become a significant area of investigation. The presented study was performed to determine the clinical efficiency and safety of hormone therapy combined with HPN in patients with gastrointestinal cancer. METHODS: One hundred patients with a Nutrition Risk Screening score of 3 or 4 undergoing surgery for gastrointestinal cancer were randomized into two groups. The patients in the control group received standard total parenteral nutrition and systemic insulin. The patients in the study group received HPN and systemic insulin in addition to pretreatment with recombinant human growth hormone and octreotide. Clinical efficiency and safety were evaluated by the measurement of hormones and protein metabolites, immune function, clinical outcome, and adverse events. Follow-ups were performed to determine the influence on prognosis. RESULTS: Treatment with recombinant human growth hormone, octreotide, and insulin in combination with HPN significantly increased protein synthesis, immune function, and metabolic tolerance, decreased infectious complications, and shortened postoperative hospital stays, but did not increase the risk of tumor development and recurrence in the study group compared with the control group. CONCLUSION: The proper short-term perioperative administration of growth hormone, somatostatin, and insulin in combination with HPN can overcome the postoperative stress response through the increase of protein synthesis to improve immune function in patients with gastrointestinal cancer after surgery.
Asunto(s)
Restricción Calórica , Neoplasias Gastrointestinales/dietoterapia , Neoplasias Gastrointestinales/tratamiento farmacológico , Hormona de Crecimiento Humana/uso terapéutico , Insulina/uso terapéutico , Octreótido/uso terapéutico , Nutrición Parenteral Total/métodos , Adulto , Anciano , Anabolizantes/efectos adversos , Anabolizantes/uso terapéutico , Restricción Calórica/efectos adversos , Método Doble Ciego , Quimioterapia Combinada/efectos adversos , Femenino , Neoplasias Gastrointestinales/cirugía , Hormona de Crecimiento Humana/efectos adversos , Humanos , Insulina/efectos adversos , Resistencia a la Insulina , Insulina Regular Porcina , Tiempo de Internación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Octreótido/efectos adversos , Nutrición Parenteral Total/efectos adversos , Atención Perioperativa , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Biosíntesis de Proteínas/efectos de los fármacos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Somatostatina/análogos & derivados , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/inmunología , Análisis de SupervivenciaRESUMEN
Congenital chylothorax is a rare condition characterized by the accumulation of lymph fluid in the pleural space that causes respiratory and circulatory dysfunctions, immune deficiencies, hypoalbuminemia, electrolyte imbalance and alterations of the coagulation. Mortality rates are elevated and can rise to 50%. Therapy consists in conservative treatment based on thoracic drainage combined with total parenteral nutrition or use of low-fat high-protein diet supplemented with medium chain triglycerides. In case of failure surgical intervention may be considered. During the last years some authors have experienced the use of octreotide with doubtful results. In no case the drug impact on insulin, GH and cortisol secretion in neonatal age has been investigated and only in one case the effect on thyroid hormones has been assessed. We report the case of a 36-week baby with congenital chylothorax treated with octreotide for 42 days. The drug was well tolerated but hormonal level measurements showed a deep depression of insulin secretion unaccompanied by alterations of glucose levels. Levels of GH and TSH showed only a transitory decrease. ACTH and cortisol remained normal. At 5 months, the measurements of hormonal levels did not show significant alterations. It is not possible to determine if such a drug played an essential role in the solution of the pleural effusion, but it is important to emphasize that a prolonged treatment with octreotide has not caused, in our case, persistent hormonal alterations.
Asunto(s)
Biomarcadores/sangre , Quilotórax/sangre , Quilotórax/tratamiento farmacológico , Hormonas/sangre , Octreótido/administración & dosificación , Hormona Adrenocorticotrópica/sangre , Quilotórax/congénito , Quilotórax/diagnóstico , Hormona de Crecimiento Humana/sangre , Humanos , Lactante , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Octreótido/efectos adversos , Tirotropina/sangre , Tirotropina/metabolismo , Tiroxina/sangre , Resultado del Tratamiento , Triyodotironina/sangreAsunto(s)
Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Tumores Neuroendocrinos/tratamiento farmacológico , Octreótido/uso terapéutico , Neoplasias Torácicas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Capecitabina , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/efectos adversos , Humanos , Interferón-alfa/administración & dosificación , Neoplasias Intestinales/tratamiento farmacológico , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Octreótido/administración & dosificación , Octreótido/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Factores de Tiempo , Resultado del TratamientoRESUMEN
Protein-losing enteropathy (PLE) is defined as a condition in which excess protein loss into the gastrointestinal lumen, due to various causes, is severe enough to produce hypoproteinemia and hypoalbuminemia. We report a 28-year-old Japanese woman with PLE. She had been diagnosed with AIDS and disseminated Mycobacterium avium complex (MAC) infection at age 26. Although highly active antiretroviral and antimycobacterial treatments helped her overcome this critical situation, 2 years after initiation of the treatments, she was readmitted to our hospital because of hypoalbuminemia and edema of the lower extremities, and she was diagnosed, by the use of double-balloon enteroscopy, with PLE due to intestinal lymphangiectasia (IL). The etiology was thought to be obstruction of the mesenteric and retroperitoneal lymphatic drainage systems by MAC lymphadenitis. Even with intensive antimycobacterial treatment, octreotide treatment as a long-acting somatostatin analogue, and a low-fat diet enriched with medium-chain triglyceride, IL was not cured during the follow-up period. In patients with AIDS, complete clinical remission of MAC (especially disseminated MAC) infection is very difficult.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones por VIH/complicaciones , VIH-1 , Linfangiectasia Intestinal/complicaciones , Infección por Mycobacterium avium-intracellulare/complicaciones , Enteropatías Perdedoras de Proteínas/terapia , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida , Adulto , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Linfangiectasia Intestinal/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Octreótido/efectos adversos , Octreótido/uso terapéutico , Enteropatías Perdedoras de Proteínas/dietoterapia , Enteropatías Perdedoras de Proteínas/tratamiento farmacológico , Enteropatías Perdedoras de Proteínas/etiología , Resultado del TratamientoRESUMEN
OBJECTIVE: Octreotide, a long-acting somatostatin analogue, has been used in the treatment of various disorders. Octreotide has significant detrimental impacts upon wound healing. We tested the hypothesis that hyperbaric oxygen therapy may overcome octreotide-mediated suppression of wound healing. DESIGN: Prospective, randomised, parallel-group animal study. METHODS: Operated rats were divided into four groups: (1) controls, (2) octreotide therapy, (3) hyperbaric oxygen therapy and (4) combination of octreotide and hyperbaric oxygen therapy. Wound healing was assessed by breaking-strength measurements, hydroxyproline levels and fibrosis scores. RESULTS: Octreotide decreased the breaking-strength measurements, hydroxyproline levels and fibrosis scores to 72%, 88% and 55%, respectively, of the control group. In the combination group, hyperbaric oxygen therapy increased breaking-strength measurements and hydroxyproline levels to 137% and 126%, respectively, of the control group. In the combination group, hyperbaric oxygen therapy tended to increase the fibrosis scores to 111% of the control group, but without statistical significance. CONCLUSION: Hyperbaric oxygen therapy tends to reverse the octreotide-induced impairment of wound healing.
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Oxigenoterapia Hiperbárica , Octreótido/efectos adversos , Vasoconstrictores/efectos adversos , Cicatrización de Heridas/efectos de los fármacos , Animales , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
In an effort to facilitate drug discovery, computational methods for facilitating the prediction of various adverse drug reactions (ADRs) have been developed. So far, attention has not been sufficiently paid to the development of methods for the prediction of serious ADRs that occur less frequently. Some of these ADRs, such as torsade de pointes (TdP), are important issues in the approval of drugs for certain diseases. Thus there is a need to develop tools for facilitating the prediction of these ADRs. This work explores the use of a statistical learning method, support vector machine (SVM), for TdP prediction. TdP involves multiple mechanisms and SVM is a method suitable for such a problem. Our SVM classification system used a set of linear solvation energy relationship (LSER) descriptors and was optimized by leave-one-out cross validation procedure. Its prediction accuracy was evaluated by using an independent set of agents and by comparison with results obtained from other commonly used classification methods using the same dataset and optimization procedure. The accuracies for the SVM prediction of TdP-causing agents and non-TdP-causing agents are 97.4 and 84.6% respectively; one is substantially improved against and the other is comparable to the results obtained by other classification methods useful for multiple-mechanism prediction problems. This indicates the potential of SVM in facilitating the prediction of TdP-causing risk of small molecules and perhaps other ADRs that involve multiple mechanisms.
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Biología Computacional/métodos , Evaluación Preclínica de Medicamentos/métodos , Torsades de Pointes/inducido químicamente , Torsades de Pointes/diagnóstico , Algoritmos , Aminoglicósidos/química , Aminoglicósidos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Biología Computacional/clasificación , Biología Computacional/estadística & datos numéricos , Interpretación Estadística de Datos , Desamino Arginina Vasopresina/efectos adversos , Desamino Arginina Vasopresina/química , Modelos Teóricos , Octreótido/efectos adversos , Octreótido/química , Torsades de Pointes/fisiopatologíaRESUMEN
BACKGROUND/AIMS: Both total parenteral nutrition and long-term octreotide treatment (> 2 months) may induce biliary sludge and lithiasis. However, the lithogenic capacity of the combination of the two treatments in the short-term is unknown. This study was undertaken to evaluate the lithogenic capacity of short-term octreotide treatment (< 1 month) in patients with acute pancreatitis who are also receiving total parenteral nutrition, and to determine the evolution of patients who develop biliary sludge and/or lithiasis. METHODOLOGY: Thirty patients with acute pancreatitis were studied (21 males, 9 females; average age: 38). All patients received total parenteral nutrition and analgesics. In a double-blind random manner, 15 patients were treated with a continuous subcutaneous administration of octreotide (200 micrograms/8 h) and a further 15 patients received placebo. Biliary sludge and/or lithiasis were examined by ultrasonography. An echographic examination of the gallbladder was performed every seven days while the patients were in hospital. They were followed up every month, when another ultrasound of the gallbladder was carried out. RESULTS: Sixteen patients (53%) developed sludge: ten (67%) from the octreotide group and six (33%) from the placebo group (P = 0.29). Two of the patients from the octreotide group had microlithiasis (P = 0.34) and a cholecystectomy was required. In the other 14 patients, sludge had disappeared by the time of the check-up performed one month after discharge. CONCLUSIONS: Short-term octreotide treatment does not increase the risk of developing biliary sludge and/or lithiasis in patients also receiving total parenteral nutrition. Biliary sludge formed during total parenteral nutrition and short-term octreotide therapy may disappear when patients begin oral intake. Therefore, preventive measures are not required.
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Colelitiasis/etiología , Octreótido/efectos adversos , Nutrición Parenteral Total/efectos adversos , Enfermedad Aguda , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Octreótido/administración & dosificación , Pancreatitis/terapia , Estudios ProspectivosRESUMEN
INTRODUCTION: Carcinoid tumors are the most common neuroendocrine tumors of the gastrointestinal tract. Surgical treatment and prognosis depend on the location of the tumor. METHOD: Between 01.01.1985 and 31.12.1999 25 patients with neuroendocrine tumors of the gastrointestinal tract or their metastases were treated in our institution. The records of these patients were reviewed retrospectively. Patients still alive were reexamined clinically. RESULTS AND CONCLUSIONS: The most frequent primary sites were the ileum and jejunum (36%), appendix (36%), stomach (12%), pancreas (8%), colon (4%) and bronchus with hepatic metastasis (4%). A malignant carcinoid syndrome was present in 8 patients. In patients with neuroendocrine tumors, curative, radical tumor removal should be attempted. Some patients with advanced disease needed some surgery for tumor debulking and resection of metastases. In non-resectable liver metastases hepatic arterial chemotherapy and chemoembolization after implantation of port catheters seem to be very beneficial therapeutic options. A fixed part of the therapeutic regime in progressive disease is adjuvant chemotherapy with 5-fluorouracil and streptozotocin and symptomatic therapy with octreotide.
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Antineoplásicos/uso terapéutico , Neoplasias Gastrointestinales/cirugía , Neoplasias Hepáticas/secundario , Tumores Neuroendocrinos/secundario , Adulto , Anciano , Antineoplásicos/efectos adversos , Quimioembolización Terapéutica , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Neoplasias Gastrointestinales/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Síndrome Carcinoide Maligno/tratamiento farmacológico , Síndrome Carcinoide Maligno/cirugía , Persona de Mediana Edad , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/cirugía , Octreótido/administración & dosificación , Octreótido/efectos adversos , Estudios Retrospectivos , Estreptozocina/administración & dosificación , Estreptozocina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Studies of octreotide have not demonstrated a consistent benefit in efficacy or safety compared with conventional therapies. This study statistically pooled existing trials to evaluate the safety and efficacy of octreotide for esophageal variceal hemorrhage. METHODS: We identified randomized trials of octreotide for variceal hemorrhage from computerized databases, scientific meeting abstracts, and the manufacturer of octreotide. Blinded reviewers abstracted the data, and a meta-analysis was performed. RESULTS: Octreotide improved control of esophageal variceal hemorrhage compared with all alternative therapies combined (relative risk [RR], 0.63; 95% confidence interval [CI], 0.51-0.77); vasopressin/terlipressin (RR, 0.58; 95% CI, 0.42-0.81); or no additional intervention/placebo (among patients that received initial sclerotherapy/banding before randomization) (RR, 0.46; 95% CI, 0.32-0.67). Octreotide had comparable efficacy to immediate sclerotherapy for control of bleeding (RR, 0.94; 95% CI, 0.55-1.62), fewer major complications than vasopressin/terlipessin (RR, 0.31; 95% CI, 0.11-0.87), and a complication profile comparable to no intervention/placebo (RR, 1.06; 95% CI, 0.72-1.55). No specific alternative therapy demonstrated a mortality benefit. CONCLUSIONS: These results favor octreotide over vasopressin/terlipressin in the control of esophageal variceal bleeding and suggest it is a safe and effective adjunctive therapy after variceal obliteration techniques. Trials are needed to determine the optimal dose, route, and duration of octreotide treatment.
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Várices Esofágicas y Gástricas/complicaciones , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Hemostáticos/uso terapéutico , Lipresina/análogos & derivados , Octreótido/uso terapéutico , Enfermedad Aguda , Hemorragia/mortalidad , Hemostáticos/efectos adversos , Humanos , Lipresina/efectos adversos , Lipresina/uso terapéutico , Octreótido/efectos adversos , Recurrencia , Terlipresina , Vasopresinas/efectos adversos , Vasopresinas/uso terapéuticoRESUMEN
Carcinoid tumors and endocrine pancreatic tumors often express somatostatin receptors (sst). Tumor spread may be visualized by sst scintigraphy using [(111)In-DTPA-D-Phe1]-octreotide. In this study, tumor targeting therapy with [(111)In-DTPA-D-Phe1]-octreotide at high doses (6 GBq every third week) was used to treat patients with sst-expressing tumors. Five patients entered the protocol and three were evaluable for response, while all could be evaluated for toxicity. Two patient responded with a significant reduction in tumor markers (> 50%). The third patient showed increasing levels of tumor markers. Side effects were expressed as depression of bone-marrow function. In one patient a grade 4 reduction in platelet count was observed requiring several thrombocyte transfusions. In another two patients platelet counts decreased significantly. We conclude that treatment with [(111)In-DTPA-D-Phe1]-octreotide can be used in patients with neuroendocrine tumors but blood parameters have to be carefully monitored to avoid severe side effects.
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Tumores Neuroendocrinos/radioterapia , Octreótido/análogos & derivados , Ácido Pentético/análogos & derivados , Anciano , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Radioisótopos de Indio/efectos adversos , Radioisótopos de Indio/uso terapéutico , Masculino , Persona de Mediana Edad , Octreótido/efectos adversos , Octreótido/uso terapéutico , Resultado del TratamientoRESUMEN
We have evaluated the long term effects and safety of Sandostatin LAR, a long acting formulation of octreotide, during 18 subsequent injections given every fourth week to 14 octreotide-sensitive acromegalic patients. The dosages (20, 30, or 40 mg) were adjusted according to GH response, side-effects, or symptom relief and assessed on day 28 after each injection. We found a stable and consistent suppression of GH and insulin-like growth factor (IGF-I) during the entire study period. Daily mean GH levels were suppressed below 2 micrograms/L in 9, to between 2-5 micrograms/L in 3, and to between 5-10 micrograms/L in 2 patients. The corresponding IGF-I values were suppressed to below 500 micrograms/L in 9 patients and to between 500-1000 micrograms/L in the remaining 5 patients. Increasing the dosage of Sandostatin LAR from 20 to 30 mg had no obvious additional effect on GH suppression, but provided a further decrease in IGF-I levels. Forty milligrams of the drug had no additional effect on GH or IGF-I compared to 30 mg. Acromegalic signs and symptoms improved during treatment. Although the fluctuations of daily mean octreotide levels were high, dosage increments caused an increase in the average serum concentration in the individual patient. Pituitary tumor size reduction was seen in all previously untreated patients (n = 4). We found only minor changes in glucose metabolism (oral glucose tolerance test and hemoglobin A1C) during treatment, but no biologically relevant changes in thyroid function (TSH, T3, and free T4). One patient developed asymptomatic gallstones, and another acquired vitamin B12 deficiency during treatment. The drug is well tolerated during long term treatment. Sandostatin LAR may well be the future medical treatment of choice for acromegalic patients.
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Acromegalia/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Octreótido/uso terapéutico , Acromegalia/fisiopatología , Adulto , Anciano , Glucemia/metabolismo , Preparaciones de Acción Retardada , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Persona de Mediana Edad , Octreótido/administración & dosificación , Octreótido/efectos adversos , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
Out of 15 patients with chronic pancreatitis (CP) treated with sandostatin, 8 patients demonstrated a complete and 6 partial response. One patient did not respond. Pain relief occurred in all of them. Side effects were registered in 3 patients (doughy stools 4 times a day throughout treatment). Normal blood levels of pancreatic enzymes, insulin secretion, parameters of blood inhibitory system did not change much because of sandostatin administration, whereas hypercoagulation got diminished. Rat experiments have revealed a trend to trypsin lowering in tissues of unaffected pancreas and more intensive inhibition of active trypsin by tissue inhibitors.