Improved understanding of renal cell carcinomas (RCC) and recent contributions in the field of RCC biology led to the development of a novel class of drugs, i.e. multiple-kinase inhibitors, targeting ...growth factor receptors (e.g. sorafenib). Sorafenib has proven significant benefit in terms of progression-free survival in a phase II trial in RCC patients. A subsequent randomized phase III study (Treatment Approaches in Renal Cancer Global Evaluation Trial) confirmed the significantly prolonged progression-free survival and improvement in the quality of life compared to patients receiving placebo. In the USA and Europe, sorafenib has been approved for the treatment of advanced RCC.
Two RCC patients on chronic hemodialysis were treated with sorafenib.
Both patients responded to sorafenib treatment. Apart from high blood pressure, a major adverse effect of sorafenib treatment, treatment was well tolerated, in agreement with previous results.
The results of our study confirm the beneficial effect of sorafenib in the treatment of RCC in our 2 patients on dialysis.
Sorafenib in renal cell carcinoma Arranz, José Ángel; Climent, Miguel Ángel; González-Larriba, José Luis ...
Critical reviews in oncology/hematology,
11/2011, Letnik:
80, Številka:
2
Journal Article
Recenzirano
Abstract Metastatic renal cell carcinoma is resistant to conventional treatment with chemotherapy. Recently the use of molecular-targeted therapies with multikinase inhibitors has been recommended as ...first-choice therapy because they inhibit cell proliferation and tumour angiogenesis. Sorafenib is a well tolerated tyrosine kinase inhibitor that initially demonstrated efficacy in the treatment of patients with metastatic RCC who progressed after immunotherapy. Expanded-access studies in Europe and North America showed the safety and efficacy of sorafenib in special populations such as elderly, renal failure and cerebral metastases, as well as patients with no prior therapy. No cross-resistance has been suggested in non-randomized trials when used in second line treatment after other targeted therapies. Ongoing clinical trials will better define the role of sorafenib in first and second line either as monotherapy or in combination, as well as the best strategies for the sequential use of this drug.
Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further ...investigation.
Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS.
123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervalsCI:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUCROC=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found.
Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers of sunitinib response.
Abstract The term castration-resistant prostate cancer (CRPC) encompasses a wide variety of patients with different prognoses. The combination of docetaxel and prednisone is considered as the ...standard first-line chemotherapy. For years, patients progressing on docetaxel have been managed with second- and third-line hormone therapies, re-treatment with docetaxel, or combined mitoxantrone and prednisone. Recently published results of four studies using different drugs: cabazitaxel (CBZ), abiraterone (AA), enzalutamide (ENZ), and radium 223, showed an increased survival in such patients. In this article, authors make some considerations about criteria guiding the choice of a second-line chemotherapy after docetaxel in patients with metastatic CRPC, and propose an algorithm based on scientific evidence and consensus for rational use of cabazitaxel in this scenario.
Introducción: La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha incidido de forma negativa en los programas de rehabilitación cardiaca (PRC) españoles. Objetivo: Este trabajo tiene como ...objetivo fundamental el analizar la posibilidad de mantenerlos abiertos y como secundario valorar si se mantienen los beneficios demostrados a nivel físico y psicológico. Métodos: Analizamos los resultados de nuestro PRC en el año 2020 (119 pacientes) y los comparamos con los del año 2019 (121 pacientes), libre de COVID-19. Se comparan distintas variables generales, y los resultados obtenidos en capacidad física, a nivel psicológico, así como las complicaciones y abandonos. Resultados: No existen diferencias significativas entre ambos grupos en la edad (61.6 vs. 61.5), sexo (mujeres: 12.6 vs. 14.8%), diagnóstico de cardiopatía isquémica (106 vs. 99) y fracción de eyección de ventrículo izquierdo (55.9 vs. 55.8%). La ansiedad media-alta fue superior al inicio (p = 0.02) y final (p = 0.002) del programa en el año 2019, así como las puntuaciones del patrón de conducta tipo A (p = 0.041 vs. 0.034). El porcentaje de depresión fue similar. Más del 95% de los pacientes del año 2020 referían miedo al contagio. La capacidad funcional aumentó, pero menos en el año 2020 (p = 0.001). La duración del programa fue superior en el año 2020 (p = 0.001). Los abandonos (15 vs. 11 pacientes) no mostraron diferencias significativas. Conclusiones: Los PRC en época COVID-19 son posibles y siguen mostrando beneficios. La duración del programa fue mayor por periodos de falta de asistencia. La menor capacidad física puede estar relacionada con el uso de la mascarilla.
Abstract Background Patients with bone metastases from advanced cancer often experience skeletal-related events (SRE), which cause substantial pain and morbidity. Denosumab, a fully human monoclonal ...antibody that inhibits RANK Ligand (RANKL), is a novel bone-targeted agent with a distinct mechanism of action relative to the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned analysis evaluates the efficacy and safety of denosumab versus zoledronic acid across three pivotal studies. Methods Patient-level data from three identically designed, randomised, double-blind, active-controlled, phase 3 trials of patients with breast cancer, prostate cancer, other solid tumours or multiple myeloma were combined. End-points included time to first SRE, time to first and subsequent (multiple) SRE, adverse events, time to disease progression and overall survival. Findings Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21 months, reducing the risk of a first SRE by 17% (hazard ratio, 0.83 95% confidence interval (CI): 0.76–0.90; P < 0.001). Efficacy was demonstrated for first and multiple events and across patient subgroups (prior SRE status; age). Disease progression and overall survival were similar between the treatments. In contrast to zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status, and was not associated with acute-phase reactions. Hypocalcaemia was more common for denosumab. Osteonecrosis of the jaw occurred at a similar rate ( P = 0.13). Conclusion Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer.
Abstract Background Papillary histology accounts for 10–15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary ...Tumor Program in Europe; ClinicalTrials.gov , NCT00688753 ) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). Methods This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. Findings Analysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23–84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval CI 25–45). In the ITT population, median PFS was 4.1 months (95% CI 3.6–5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4–28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1–11.0) and 5.1 months (95% CI 3.3–5.5), respectively, and median OS was 28.0 months (95% CI 7.6–not estimable) and 24.2 months (95% CI 15.8–32.8), respectively. Common grade >2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%). Interpretation Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour.
Introduction
Sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, delays disease progression, with a median overall survival (OS) of more than 2 years, improves quality of life and ...is becoming the first-line standard of care for metastatic renal carcinoma (mRCC).
Purpose
To assess the economic value of sunitinib as first-line therapy in mRCC within the Spanish healthcare system.
Methods
An adapted Markov model with a 10-year time horizon was used to analyse the cost effectiveness of sunitinib vs. sorafenib (SFN) and bevacizumab/interferon-α (BEV/IFN) as first-line mRCC therapy from the Spanish third-party payer perspective. Progression-free survival (PFS) and OS data from sunitinib, SFN and BEV/IFN pivotal trials were extrapolated to project survival and costs in 6-week cycles. Results, in progression-free life-years (PFLY), life years (LY) and quality-adjusted life-years (QALY) gained, expressed as incremental cost-effectiveness ratios (ICER) with costs and benefits discounted annually at 3%, were obtained using deterministic and probabilistic analyses.
Results
Sunitinib was more effective and less costly than both SFN (gains of 0.52 PFLY, 0.16 LY, 0.17 QALY) and BEV/IFN (gains of 0.19 PFLY, 0.23 LY, 0.16 QALY) with average cost savings/patients of €,124 and €23,218, respectively. Using a willingness-to-pay (WTP) threshold of €50,000/QALY, sunitinib achieved an incremental net benefit (INB) of €9,717 and €31,211 compared with SFN and BEV/IFN, respectively. At this WTP, the probability of sunitinib providing the highest INB was 75%.
Conclusion
Our analysis suggests that sunitinib is a cost-effective alternative to other targeted therapies as first-line mRCC therapy in the Spanish healthcare setting.
Purpose
This exploratory phase II clinical trial evaluated the antitumor activity, safety profile and pharmacokinetics of PM00104 (Zalypsis
®
) 3 mg/m
2
1 h every 3-week intravenous infusion in ...patients with advanced and/or metastatic urothelial carcinoma progressing after first-line platinum-based chemotherapy.
Methods
The primary efficacy end point was the disease control rate (DCR), defined as the percentage of patients with confirmed objective response or progression-free at 3 months, according to the response evaluation criteria in solid tumors.
Results
In a first stage (
n
= 19 patients evaluable for efficacy), only one patient achieved DCR (stable disease as best response and progression-free survival of 3.1 months). According to the 2-stage design used, the primary efficacy objective was unmet, and therefore, the trial was finalized without opening the second stage. The most common adverse events related to PM00104 were fatigue, anorexia, nausea, troponin I increase and neutropenia, which were transient and manageable with dose modifications or administration delays. Mean PK results (
C
max
= 48.57 μg/l and area under the curve (AUC) = 154.97 h μg/l) were similar to those observed in a previous phase I trial evaluating the same dose and schedule. Few troponin I concentrations were higher than 0.10 ng/ml, and none of them were related to parameters of PM00104 exposure such as AUC or
C
max
.
Conclusions
No recommendation is given for further evaluation of PM00104 as single-agent treatment of patients with pretreated advanced and/or metastatic urothelial carcinoma. No new safety signals were observed.
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