Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Gynecol Oncol ; 150(3): 478-486, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30068487

RESUMEN

PURPOSE: Preclinical studies performed in our laboratory have shown that high-dose selenium inhibits the development of carboplatin drug resistance in an ovarian cancer mouse xenograft model. Based on these data, as well as the potential serious toxicities of supranutritional doses of selenium, a phase I trial of a combination of selenium/carboplatin/paclitaxel was designed to determine the maximum tolerated dose, safety, and effects of selenium on carboplatin pharmacokinetics in the treatment of chemo-naive women with gynecologic cancers. Correlative studies were performed to identify gene targets of selenium. METHODS: Chemo-naïve patients with gynecologic malignancy received selenious acid IV on day 1 followed by carboplatin IV and paclitaxel IV on day 3. A standard 3 + 3 dose-escalating design was used for addition of selenium to standard dose chemotherapy. Concentrations of selenium in plasma and carboplatin in plasma ultrafiltrate were analyzed. RESULTS: Forty-five patients were enrolled and 291 treatment cycles were administered. Selenium was administered as selenious acid to 9 cohorts of patients with selenium doses ranging from 50 µg to 5000 µg. Grade 3/4 toxicities included neutropenia (66.7%), febrile neutropenia (2.2%), pain (20.0%), infection (13.3%), neurologic (11.1%), and pulmonary adverse effects (11.1%). The maximum tolerated dose of selenium was not reached. Selenium had no effect on carboplatin pharmacokinetics. Correlative studies showed post-treatment downregulation of RAD51AP1, a protein involved in DNA repair, in both cancer cell lines and patient tumors. CONCLUSION: Overall, the addition of selenium to carboplatin/paclitaxel chemotherapy is safe and well tolerated, and does not alter carboplatin pharmacokinetics. A 5000 µg dose of elemental selenium as selenious acid is suggested as the dose to be evaluated in a phase II trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/farmacocinética , Línea Celular Tumoral , Neutropenia Febril Inducida por Quimioterapia/etiología , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/sangre , Humanos , Infecciones/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Dosis Máxima Tolerada , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Proteínas de Unión al ARN , Criterios de Evaluación de Respuesta en Tumores Sólidos , Ácido Selenioso/administración & dosificación , Ácido Selenioso/farmacocinética , Selenio/sangre , Selenoproteína P/sangre
2.
Ann Vasc Surg ; 29(1): 127.e11-5, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25305425

RESUMEN

BACKGROUND: Vascular blowout syndrome is a well-known, life-threatening condition complicating advanced-stage head and neck malignancies but has rarely been reported in the gynecologic oncology realm in association with the femoral circulation. A 50-year-old woman with metastatic vulvar squamous cell carcinoma presented with left threatened femoral arterial blowout, secondary to an exophytic neoplastic mass originating from the left inguinal lymph nodes. METHODS: Bland embolization of the tumor as well as 3 vessel covered stent revascularization was successfully performed with excellent tumor devascularization and reinstitution of arterial integrity. RESULTS: Successful devascularization of the tumor, with no non-target embolization was achieved, with excellent apposition and deployment of 3 covered stents in the femoral artery bifurcation. CONCLUSION: We present a unique case of threatened femoral artery blowout syndrome in the setting of metastatic vulvar carcinoma requiring various endovascular techniques for palliation. These endovascular techniques can be invaluable in minimally invasive palliation of advanced stage neoplasms abutting the iliofemoral circulation.


Asunto(s)
Carcinoma de Células Escamosas/secundario , Embolización Terapéutica , Arteria Femoral/patología , Ganglios Linfáticos/patología , Enfermedad Arterial Periférica/terapia , Neoplasias de la Vulva/patología , Angioplastia de Balón/instrumentación , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/diagnóstico por imagen , Terapia Combinada , Femenino , Arteria Femoral/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Cuidados Paliativos , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/etiología , Rotura Espontánea , Stents , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
3.
Int J Gynecol Cancer ; 24(9): 1636-41, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25304678

RESUMEN

OBJECTIVE: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. MATERIALS AND METHODS: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m, days 1 to 4, and intravenous paclitaxel, 175 mg/m, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. RESULTS: Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0-7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5-26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years. CONCLUSIONS: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Isotretinoína/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Antivirales/uso terapéutico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Fármacos Dermatológicos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Interferón alfa-2 , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Proteínas Recombinantes/uso terapéutico , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología
4.
Semin Oncol ; 36(3): 250-7, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19460582

RESUMEN

Ovarian cancer in the adolescent and young adult (AYA) population is a disease that is distinctly different with regard to risk factors, genetics, and pathology when compared to ovarian cancers occurring in older women. This article will review the theories behind ovarian carcinogenesis and attempt to elucidate why these tumors exhibit their unique biologic characteristics. Knowledge of these differences will allow us to begin to develop strategies for future research endeavors enabling improved survival in AYA women diagnosed with ovarian cancer.


Asunto(s)
Neoplasias Ováricas , Adolescente , Adulto , Factores de Edad , Anticonceptivos Orales/uso terapéutico , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Glandulares y Epiteliales/epidemiología , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Factores de Riesgo
5.
Cancer Chemother Pharmacol ; 71(6): 1635-43, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23636448

RESUMEN

PURPOSE: The metabolism of pazopanib is primarily mediated by CYP3A4. The solubility of pazopanib is pH-dependent, and an elevated gastric pH may decrease its bioavailability. This study evaluated the effect of a potent CYP3A4 inhibitor, ketoconazole, and the proton pump inhibitor esomeprazole on the pharmacokinetics and safety of pazopanib and its metabolites. METHODS: In Arm A, patients received pazopanib 400 mg alone once daily for 7 days followed by pazopanib 400 mg plus ketoconazole 400 mg once daily for 5 days. In Arm B, patients received pazopanib 800 mg once daily for 7 days, followed by pazopanib 800 mg plus esomeprazole 40 mg once daily for 5 days, and then pazopanib alone on the last day. RESULTS: Arm A enrolled 21 patients. In the presence of ketoconazole, mean area under the plasma concentration-time curve 24 h post-dose (AUC(0-24)) and mean maximum observed concentration (C max) of pazopanib increased by 66 and 45 %, respectively; mean AUC(0-24) and C max for pazopanib metabolites were lower or remained unchanged. Arm B enrolled 13 patients. In the presence of esomeprazole, mean pazopanib AUC(0-24) and C max decreased by 40 and 42 %, respectively; mean values of those parameters for metabolites of pazopanib also decreased. CONCLUSIONS: Concomitant use of pazopanib with a strong CYP3A4 inhibitor should be avoided. If coadministration is necessary, pazopanib should be reduced to 400 mg. Concomitant use of pazopanib and proton pump inhibitors should also be avoided. Alternative dosing regimens that do not increase gastric pH at the time of pazopanib dosing should be considered.


Asunto(s)
Inhibidores de la Angiogénesis/farmacocinética , Esomeprazol/farmacología , Cetoconazol/farmacología , Neoplasias/tratamiento farmacológico , Inhibidores de la Bomba de Protones/farmacología , Pirimidinas/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Citocromo P-450 CYP3A , Inhibidores del Citocromo P-450 CYP3A , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Interacciones Farmacológicas , Esomeprazol/administración & dosificación , Esomeprazol/efectos adversos , Femenino , Humanos , Indazoles , Cetoconazol/administración & dosificación , Cetoconazol/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias/metabolismo , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico
6.
J Clin Oncol ; 30(19): 2348-53, 2012 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-22529266

RESUMEN

PURPOSE: To determine the maximum-tolerated dose (MTD) and assess safety, pharmacokinetics, pharmacodynamics, and evidence of antitumor activity of RO4929097, a gamma secretase inhibitor of Notch signaling in patients with advanced solid malignancies. PATIENTS AND METHODS: Patients received escalating doses of RO4929097 orally on two schedules: (A) 3 consecutive days per week for 2 weeks every 3 weeks; (B) 7 consecutive days every 3 weeks. To assess reversible CYP3A4 autoinduction, the expanded part of the study tested three dosing schedules: (B) as above; modified A, 3 consecutive d/wk for 3 weeks; and (C) continuous daily dosing. Positron emission tomography scans with [(18)F]fluorodeoxyglucose (FDG-PET) were used to assess tumor metabolic effects. RESULTS: Patients on schedule A (n = 58), B (n = 47), and C (n = 5; expanded cohort) received 302 cycles of RO4929097. Common grade 1 to 2 toxicities were fatigue, thrombocytopenia, fever, rash, chills, and anorexia. Transient grade 3 hypophosphatemia (dose-limiting toxicity, one patient) and grade 3 pruritus (two patients) were observed at 27 mg and 60 mg, respectively; transient grade 3 asthenia was observed on schedule A at 80 mg (one patient). Tumor responses included one partial response in a patient with colorectal adenocarcinoma with neuroendocrine features, one mixed response (stable disease) in a patient with sarcoma, and one nearly complete FDG-PET response in a patient with melanoma. Effect on CYP3A4 induction was observed. CONCLUSION: RO4929097 was well tolerated at 270 mg on schedule A and at 135 mg on schedule B; the safety of schedule C has not been fully evaluated. Further studies are warranted on the basis of a favorable safety profile and preliminary evidence of clinical antitumor activity.


Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Benzazepinas/uso terapéutico , Neoplasias/tratamiento farmacológico , Receptores Notch/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Benzazepinas/efectos adversos , Benzazepinas/farmacocinética , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/enzimología , Neoplasias/metabolismo , Neoplasias/patología , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA