Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Oncologist ; 24(4): 491-497, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30867244

RESUMEN

BACKGROUND: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). SUBJECTS, MATERIALS, AND METHODS: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. RESULTS: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2-12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. CONCLUSION: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. IMPLICATIONS FOR PRACTICE: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors' knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/secundario , Femenino , Estudios de Seguimiento , Humanos , Indazoles , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Calidad de Vida , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
2.
BMC Cancer ; 19(1): 794, 2019 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-31409302

RESUMEN

BACKGROUND: PALETTE is a phase 3 trial that demonstrated single-agent activity of pazopanib in advanced soft tissue sarcomas (aSTS). We performed retrospective subgroup analyses to explore potential relationships between patient characteristics, prior lines of therapy, dose intensity, and dose modifications on safety and efficacy of pazopanib in aSTS. METHODS: PALETTE compared pazopanib with placebo in patients with aSTS (age ≥ 18 years) whose disease had progressed during or following prior chemotherapy. In these subgroup analyses, median progression-free survival (mPFS) among patients receiving pazopanib was the efficacy outcome of interest. Adverse events (AEs) were also compared within subgroups. All analyses were descriptive and exploratory. RESULTS: A total of 246 patients received pazopanib in the PALETTE study. The mPFS was longer in patients who had only 1 prior line versus 2+ prior lines of therapy (24.7 vs 18.9 weeks, respectively); AE rates were similar regardless of number of prior lines of therapy. The mPFS was similar in patients aged < 65 and ≥ 65 y (20.0 and 20.1 weeks, respectively). Although AEs leading to study discontinuation were higher in older patients (≥65 y, 30%; < 65 y, 17%), rates of dose reductions, dose interruptions, and serious AEs were similar between the 2 age groups. No reduction in mPFS was noted in patients requiring dose reductions or dose interruptions to manage toxicities. CONCLUSIONS: Longer mPFS was observed in patients receiving pazopanib following only 1 line of therapy. Additionally, mPFS with pazopanib was maintained regardless of patient age or dose modifications used to manage toxicity. TRIAL REGISTRATION: NCT00753688 , first posted September 16, 2008 (registered prospectively).


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Pirimidinas/uso terapéutico , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Sarcoma/mortalidad , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Análisis de Supervivencia , Resultado del Tratamiento
3.
Clin Orthop Relat Res ; 474(5): 1234-44, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26932738

RESUMEN

BACKGROUND: There is a medical need for therapies that improve hip fracture healing. Teriparatide (Forteo(®)/ Forsteo(®), recombinant human parathyroid hormone) is a bone anabolic drug that is approved for treatment of osteoporosis and glucocorticoid-induced osteoporosis in men and postmenopausal women at high fracture risk. Preclinical and preliminary clinical data also suggest that teriparatide may enhance bone healing. QUESTIONS/PURPOSES: We wished to test the hypotheses that treatment with teriparatide versus placebo would improve femoral neck fracture healing after internal fixation as measured by (1) frequency of revision surgery, (2) radiographic fracture healing, and (3) other outcomes including pain control, gait speed, and safety. METHODS: We initiated two separate, but identically designed, clinical trials to meet FDA requirements to provide substantial evidence to support approval of a new indication. The two prospective, randomized double-blind, placebo-controlled Phase III studies were designed to evaluate the effect of subcutaneous teriparatide (20 µg/day) for 6 months versus placebo on fracture healing at 24 months. The trials were conducted concurrently with a planned enrollment of 1220 patients per trial. However, enrollment was stopped owing to very slow patient accrual, and an a priori decision was made to pool the results of those studies for statistical analyses before study completion; pooling was specified in both protocols. Randomization was stratified by fixation (sliding hip screw or multiple cancellous screws) and fracture type (displaced or nondisplaced). An independent Central Adjudication Committee reviewed revision surgical procedures and radiographs. A total of 159 patients were randomized in the two trials (81 placebo, 78 teriparatide). The combined program had very low power to detect the originally expected treatment effect but had approximately 80% power to detect a larger difference of 12% between treatment groups for risk of revision surgery. RESULTS: The proportion of patients undergoing revision surgery at 12 months was 14% (11 of 81) in the placebo group versus 17% (13 of 78) in the teriparatide group. Central Adjudication Committee review excluded two of these patients treated with placebo from the primary analysis. After exclusions, the proportion of patients who did not undergo revision surgery at 12 months (primary endpoint) was not different between the study and placebo groups, at 88% in the placebo group (90% CI, 0.79-0.93) versus 84% in the teriparatide group (90% CI, 0.75-0.90; p = 0.743). There also were no differences between groups in the proportion of patients achieving radiographic fracture healing at 12 months (75% [61 of 81] placebo versus 73% [57 of 78] teriparatide; odds ratio, 0.89; 90% CI, 0.46-1.72; p = 0.692) or in measures of pain control (such as pain during ambulation, 92% [55 of 62] placebo versus 91% [52 of 57] teriparatide; odds ratio, 0.91; 90% CI, 0.25-3.37; p = 0.681). The frequency of patients reporting adverse events was 49% [40 of 81] in the placebo group versus 45% [35 of 78] in the teriparatide group (p = 0.634) during the 6-month treatment period. CONCLUSIONS: The small sample size limited this study's power to detect potential differences, and the results are exploratory. With the patients available, teriparatide did not decrease the risk of revision surgery, improve radiographic signs of fracture healing, or decrease pain compared with the placebo. The adverse event data observed were consistent with the teriparatide safety profile. Functional and health outcome data from the studies may help improve our understanding of patients recovering from femoral neck fractures. Further large controlled studies are required to determine the effect of teriparatide on fracture healing. LEVEL OF EVIDENCE: Level II, prospective study.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Fracturas del Cuello Femoral/terapia , Cuello Femoral/efectos de los fármacos , Cuello Femoral/cirugía , Fijación Interna de Fracturas , Curación de Fractura/efectos de los fármacos , Teriparatido/uso terapéutico , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Conservadores de la Densidad Ósea/efectos adversos , Tornillos Óseos , Terapia Combinada , Método Doble Ciego , Femenino , Fracturas del Cuello Femoral/diagnóstico , Fracturas del Cuello Femoral/fisiopatología , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/fisiopatología , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Marcha , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Dimensión del Dolor , Dolor Postoperatorio/etiología , Estudios Prospectivos , Radiografía , Recuperación de la Función , Reoperación , Factores de Riesgo , Teriparatido/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
4.
Ann Med Surg (Lond) ; 60: 92-101, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33133591

RESUMEN

BACKGROUND: Thyroid dysfunction has a negative impact on coronary artery diseases (CAD) through several changes in its risk factors like dyslipidemia, glucose intolerance, and components of metabolic syndrome. Parental history of premature CAD may be an important risk factor for their offspring. OBJECTIVE: To investigate whether overt and subclinical hypothyroidism and the risk of atherosclerosis are present in adults with parental history of CAD. MATERIALS AND METHODS: This case control study included 135 hypothyroid patients and 100 age-sex matched controls. Data were analyzed regarding CAD risk factors, hormonal and biochemical measures including retinol Binding Protein-4, fasting serum insulin, high-sensitivity C-reactive protein, lipid profile, fasting serum glucose, and serum malondialdehyde. RESULTS: Parental history of CAD was significantly higher in overt hypothyroidism than subclinical group (P = 0.001). The level of RBP-4 in hypothyroid patients was significantly higher than euthyroid subjects (P = 0.03), and was higher in hypothyroid patients with positive parental history of CAD (p = 0.01). There were positive relationships between RBP-4 and related cardiovascular risk factors and with hypothyroidism, its sensitivity and specificity were 47.9% and 42.5% respectively. The positive predictive value was 60.8% and the negative predictive value was 30.4%. Hypothyroid patients with parental history of CAD had a risk of 3.7 times more than the euthyroid subjects. CONCLUSIONS: In hypothyroidism patients, parental history of CAD is a predictor of future coronary events and the related risk factors. RBP-4 is positively correlated with waist circumference, BMI, lipid profile, High-sensitivity CRP, MDA, fasting serum glucose, fasting serum insulin, HOMA indices and TSH.

5.
Clin Genitourin Cancer ; 17(3): e526-e533, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31196680

RESUMEN

INTRODUCTION: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). PATIENTS AND METHODS: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. RESULTS: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. CONCLUSIONS: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. ≥ 2) to more accurately predict outcomes.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/secundario , Femenino , Estudios de Seguimiento , Humanos , Indazoles , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Seguridad del Paciente , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto Joven
6.
Clin Genitourin Cancer ; 16(4): 293-297, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29653813

RESUMEN

BACKGROUND: Pazopanib is among the current standards of care for first-line treatment of patients with unresectable advanced renal-cell carcinoma (aRCC) or metastatic renal-cell carcinoma. This real-world study aimed to characterize those with long-term response to pazopanib in the treatment of aRCC in a community oncology setting, and to identify predictors of long-term response. PATIENTS AND METHODS: aRCC patients treated with first-line pazopanib were classified as having long-term or non-long-term response (progression-free survival [PFS] of ≥ 18 or < 18 months, respectively). Baseline patient demographics and clinical characteristics were evaluated and compared between the 2 groups. Differences in PFS and overall survival were also evaluated. RESULTS: A total of 153 eligible patients were identified, of which 33 (21.6%) and 120 (78.4%) patients were identified as having disease with long-term and non-long-term response, respectively. The median PFS for those with long-term response was 27.2 months (95% confidence interval [CI], 23.0-35.2) versus 6.9 months (95% CI, 5.0-8.6) for those with non-long-term response. Median overall survival was not reached (NR) for those with long-term response (95% CI, NR to 39.1) compared to 15.3 months (95% CI, 12.3-21.6) for those with non-long-term response. Baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 (vs. ECOG PS of 1 and ≥ 2) and history of nephrectomy were identified as significant predictors of long-term response to pazopanib. CONCLUSION: In aRCC patients treated with first-line pazopanib, 22% had a long-term response. Significant predictors of long-term response included an ECOG PS of 0 and a history of nephrectomy.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Indazoles , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
7.
J Hematol Oncol ; 11(1): 69, 2018 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-29788981

RESUMEN

BACKGROUND: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations. METHODS: Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off). RESULTS: Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmar-plantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most non-hematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%). CONCLUSIONS: A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00720941 , Registered July 22, 2008 ClinicalTrials.gov, NCT01147822 , Registered June 22, 2010.


Asunto(s)
Carcinoma de Células Renales/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etnología , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Sunitinib/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma de Células Renales/etnología , Carcinoma de Células Renales/patología , Femenino , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pirimidinas/efectos adversos , Sulfonamidas/efectos adversos , Sunitinib/efectos adversos , Población Blanca , Adulto Joven
8.
Lancet Diabetes Endocrinol ; 3(12): 948-57, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26516121

RESUMEN

BACKGROUND: Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls and low muscle strength and power. METHODS: In this proof-of-concept, randomised, placebo-controlled, double-blind, parallel, multicentre, phase 2 study, we recruited patients aged 75 years or older who had fallen in the past year from 21 investigator sites across Argentina, Australia, France, Germany, Sweden, and the USA. Eligible patients had low performance on hand grip strength and chair rise tests, tested with the procedure described by Guralnik and colleagues. Participants were stratified by country, age, hand grip strength, and performance on the chair rise test, and were randomly assigned (1:1) by a computer-generated random sequence to receive subcutaneous injections of placebo or 315 mg LY at weeks 0 (randomisation visit), 4, 8, 12, 16, and 20, followed by 16 weeks observation. The primary outcome was change in aLBM from baseline to 24 weeks. We measured physical performance as secondary outcomes (four-step stair climbing time, usual gait speed, and time to rise five times from a chair without arms, or with arms for participants unable to do it without arms) and exploratory outcomes (12-step stair climbing test, 6-min walking distance, fast gait speed, hand grip strength, and isometric leg extension strength). Efficacy analyses included all randomly assigned patients who received at least one dose and had a baseline and at least one subsequent measure. The primary analysis and all other tests of treatment effect (except physical performance tests) were done at a two-sided alpha level of 0·05. Tests of treatment effect on physical performance tests were done at a pre-specified two-sided alpha level of 0·1. This trial is registered with ClinicalTrials.gov, number NCT01604408. FINDINGS: Between June 19, 2012, and Dec 12, 2013, we screened 365 patients. 99 were randomly assigned to receive placebo and 102 to receive LY. Treatment was completed in 85 (86%) of patients given placebo and in 82 (80%) given LY. At 24 weeks, the least-squares mean change in aLBM was -0·123 kg (95% CI -0·287 to 0·040) in the placebo group and 0·303 kg (0·135 to 0·470) in the LY group, a difference of 0·43 kg (95% CI 0·192 to 0·660; p<0·0001). Stair climbing time (four-step and 12-step tests), chair rise with arms, and fast gait speed improved significantly from baseline to week 24 with differences between LY and placebo of respectively -0·46 s (p=0·093), -1·28 s (p=0·011), -4·15 s (p=0·054), and 0·05 m/s (p=0·088). No effect was detected for other performance-based measures. Injection site reactions were recorded in nine (9%) patients given placebo and in 31 (30%) patients given LY (p<0·0001), and were generally mild, and led to treatment discontinuation in two patients given LY. INTERPRETATION: Our findings show LY treatment increases lean mass and might improve functional measures of muscle power. Although additional studies are needed to confirm these results, our data suggest LY should be tested for its potential ability to reduce the risk of falls or physical dependency in older weak fallers. FUNDING: Eli Lilly and Company.


Asunto(s)
Accidentes por Caídas , Anticuerpos Monoclonales Humanizados/uso terapéutico , Debilidad Muscular/tratamiento farmacológico , Músculo Esquelético/efectos de los fármacos , Miostatina/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Método Doble Ciego , Femenino , Marcha/efectos de los fármacos , Fuerza de la Mano , Humanos , Inyecciones Subcutáneas , Masculino , Miostatina/inmunología , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA