A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer

A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. Systematic searching (upto April 2005) identified seven randomised controlled trials. One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline. Two other chemotherapy regimens that included docetaxel with estramustine also showed improved outcomes in comparison with mitoxantrone plus prednisone. Three trials that compared mitoxantrone plus corticosteroids with corticosteroids alone were identified and their results for overall survival combined, which showed very little difference between the two groups. The addition of clodronate to mitoxantrone plus prednisone showed no significant differences in comparison with mitoxantrone plus prednisone alone. The evidence suggests that chemotherapy regimens containing 3-weekly docetaxel are superior to mitoxantrone or corticosteroids alone

Real-world Experience With Sunitinib Treatment in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to Risk Score.

BACKGROUND: ADONIS is an ongoing observational study in 9 European countries, designed to evaluate treatment patterns/outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib and/or second-line axitinib post sunitinib. We present an evaluation of sunitinib efficacy by risk group, in the real-world setting examined in ADONIS. PATIENTS AND METHODS: Patients were enrolled at the start of first-line sunitinib treatment or second-line axitinib post sunitinib treatment. Evaluation of sunitinib efficacy was assessed by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center risk criteria. RESULTS: For all patients in this analysis (N = 467), the median progression-free survival was 23.8 months (95% confidence interval [CI], 16.5-28.5 months), 11.8 months (95% CI, 8.1-17.4 months), and 4.6 months (95% CI, 2.5-7.7 months) for IMDC favorable-, intermediate-, and poor-risk groups, respectively. The median overall survival was 97.1 months (95% CI, 46.3 months-not evaluable [NE]), 33.5 months (95% CI, 20.5-46.6 months), and 10.0 months (95% CI, 4.5-19.8 months) for the respective risk groups. Data on individual risk factors were available for a subgroup of patients, allowing analysis by intermediate risk by 1 versus 2 risk factors. When including this subgroup (n = 120), the median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 months (95% CI, 16.3 months-NE), 20.5 months (15.5 months-NE), and 15.1 months (4.1 months-NE), respectively. CONCLUSIONS: For patients overall and by risk-group stratification, survival estimates were aligned with previously published data. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration of outcome data from different sources is needed to confirm these observations

Cloud thermodynamic phase inferred from merged POLDER and MODIS data

International audienceThe global spatial and diurnal distribution of cloud properties is a key issue for understanding the hydrological cycle, and critical for advancing efforts to improve numerical weather models and general circulation models. Satellite data provides the best way of gaining insight into global cloud properties. In particular, the determination of cloud thermodynamic phase is a critical first step in the process of inferring cloud optical and microphysical properties from satellite measurements. It is important that cloud phase be derived together with an estimate of the confidence of this determination, so that this information can be included with subsequent retrievals (optical thickness, effective particle radius, and ice/liquid water content). In this study, we combine three different and well documented approaches for inferring cloud phase into a single algorithm. The algorithm is applied to data obtained by the MODIS (MODerate resolution Imaging Spectroradiometer) and POLDER3 (Polarization and Directionality of the Earth Reflectance) instruments. It is shown that this synergistic algorithm can be used routinely to derive cloud phase along with an index that helps to discriminate ambiguous phase from confident phase cases. The resulting product provides a semi-continuous confidence index ranging from confident liquid to confident ice instead of the usual discrete classification of liquid phase, ice phase, mixed phase (potential combination of ice and liquid particles), or simply unknown phase clouds. This approach is expected to be useful for cloud assimilation and modeling efforts while providing more insight into the global cloud properties derived from satellite data

Непрямое сравнение эффективности и безопасности апалутамида и даролутамида для лечения неметастатического кастрационнорезистентного рака предстательной железы по результатам двух независимых исследований с поправкой на разницу между популяциями пациентов

.Введение. Апалутамид и даролутамид являются ингибиторами андрогенных рецепторов нового поколения, которые продемонстрировали превосходную эффективность у пациентов с неметастатическим кастрационно-резистентным раком предстательной железы, получающих андрогендепривационную терапию (АДТ). На сегодняшний день нет исследований по прямому сравнению этих 2 препаратов.Цель исследования – непрямое сравнение эффективности и переносимости апалутамида и даролутамида.Материалы и методы. Был применен метод согласованного скорректированного непрямого сравнения (matchingadjusted indirect comparison, MAIC) данных рандомизированного плацебо-контролируемого исследования III фазы SPARTAN (апалутамид + АДТ), которые были уравновешены по основным исходным клиническим параметрам, с опубликованными обобщенными данными исследования ARAMIS (даролутамид + АДТ) для их сопоставления. Для оценки всех конечных точек эффективности, включая выживаемость без метастазирования, повышение уровня простатического специфического антигена (ПСА), выживаемость без прогрессирования, а также общую выживаемость, были рассчитаны отношения рисков (ОР) и 95 % доверительные интервалы (ДИ). Для оценки конечных точек по безопасности (частота нежелательных явлений и серьезных нежелательных явлений) рассчитывали отношения шансов.Результаты. Перед уравновешиванием данных в исследованиях SPARTAN и ARAMIS наблюдались значимые различия по уровню ПСА (медиана 7,8 нг/мл против 9,2 нг/мл), числу пациентов со статусом 1 по шкале Eastern Cooperative Oncology Group (23 % против 31 %), частоте использования препаратов для модификации костной ткани (10 % против 4 %), медиане времени с момента установления первичного диагноза (94,9 мес против 85,4 мес) и числу пациентов из США (35 % против 12 %) и Европы (50 % против 64 %). После уравновешивания данных (n = 455) мы установили, что режим, включающий апалутамид + АДТ, с высокой долей вероятности более эффективен, чем даролутамид + АДТ, по выживаемости без метастазирования (98,3 %; ОР 0,70; 95 % ДИ 0,51–0,98), повышениюуровня ПСА (~100 %; ОР 0,46; 95 % ДИ 0,33–0,64) и выживаемости без прогрессирования (93,2 %; ОР 0,79; 95 % ДИ 0,59–1,08). Показатели общей выживаемости и переносимости не различались значительно при сравнении групп апалутамид + АДТ и даролутамид + АДТ.Заключение. Результаты анализа данных 2 важнейших исследований III фазы по неметастатическому кастрационно-резистентному раку предстательной железы с помощью метода MAIC указывают на то, что апалутамид + АДТ является более эффективной схемой лечения, чем даролутамид + АДТ, по показателям выживаемости без прогрессирования и повышению уровня ПСА, в то время как общая выживаемость и профиль безопасности этих 2 режимов не различаются.

Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia: Combined Subgroup Analyses of the RECORD-1 and REACT Trials

In this study we examined the outcome of metastatic renal cell cancer patients with everolimus treatment-related hyperglycemia and hypercholesterolemia. All patients were treated in 2 large, international prospective trials, RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC). Patients who experienced these events might have experienced an improved response to everolimus. Background Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Patients and Methods Adults with vascular endothelial growth factor–refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia. Results In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant. Conclusion Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies

Metastatic collecting duct carcinoma of the kidney treated with sunitinib

Collecting duct carcinoma (CDC) of the kidney is a rare and aggressive malignant tumor arising from the distal collecting tubules which has been shown to have a poor response to several kinds of systemic therapy. We present a case of metastatic CDC that responded favorably to a multiple tyrosine kinase inhibitor, sunitinib, achieving a partial response in both lung and skeletal metastases. To our knowledge, this is the first report showing therapeutic activity of sunitinib against CDC. Considering these findings, it would be worthwhile prospectively investigating the role of multiple tyrosine kinase inhibitors, particularly sunitinib, in the management of metastatic CDC

Cloud thermodynamic phase inferred from merged POLDER and MODIS data

The global spatial and diurnal distribution of cloud properties is a key issue for understanding the hydrological cycle, and critical for advancing efforts to improve numerical weather models and general circulation models. Satellite data provides the best way of gaining insight into global cloud properties. In particular, the determination of cloud thermodynamic phase is a critical first step in the process of inferring cloud optical and microphysical properties from satellite measurements. It is important that cloud phase be derived together with an estimate of the confidence of this determination, so that this information can be included with subsequent retrievals (optical thickness, effective particle radius, and ice/liquid water content). In this study, we combine three different and well documented approaches for inferring cloud phase into a single algorithm. The algorithm is applied to data obtained by the MODIS (MODerate resolution Imaging Spectroradiometer) and POLDER3 (Polarization and Directionality of the Earth Reflectance) instruments. It is shown that this synergistic algorithm can be used routinely to derive cloud phase along with an index that helps to discriminate ambiguous phase from confident phase cases. The resulting product provides a semi-continuous index ranging from confident liquid to confident ice instead of the usual discrete classification of liquid phase, ice phase, mixed phase (potential combination of ice and liquid particles), or simply unknown phase clouds. The index value provides simultaneously information on the phase and the associated confidence. This approach is expected to be useful for cloud assimilation and modeling efforts while providing more insight into the global cloud properties derived from satellite data