483 research outputs found
Gulati S.C., Jules-Elysee K., Whitmarsch K., Yahalom J., Reich L., Crown J., Motzer R., Coleman M., Lemoli R.M., Clarkson B.D., Portlock C., Gee T. and Mendelsohn J.
No full textCisplatin-based chemotherapy of testicular cancer - Two decades after a major breakthrough
No full textTwo decades ago the introduction of cisplatin-based combination chemotherapy has dramatically improved the prognosis of patients with metastatic testicular cancer, At present 3 cycles of cisplatin, etoposide and bleomycin are considered as standard treatment for good-risk metastatic disease. Outside of clinical trials patients in the intermediate and poor prognosis categories should receive 4 cycles of this standard regimen, Clinical trials currently evaluate the role of high-dose chemotherapy in first-line treatment of high-risk patients and in the salvage setting, Post-chemotherapy resection of tumor residuals remains an important part of therapy. Attention should be focused on long-term toxicity of therapy and the occurrence of late relapse
The role of tivozanib in advanced renal cell carcinoma therapy
No full textIntroduction: The efficacy of VEGF-targeting therapies in clinical trials led to their recommendation in clinical guidelines for use across the advanced or metastatic renal cell carcinoma (RCC) treatment landscape, however, tolerability (including off-target effects) has remained a challenge. Tivozanib is a selective inhibitor of all three VEGFRs, with limited off-target interaction, which demonstrates efficacy with improved tolerability relative to multikinase VEGFR-TKIs. Areas covered: Covered here is the clinical development of tivozanib in advanced RCC, including the pivotal Phase III, multicenter, open-label, randomized clinical study comparing tivozanib with sorafenib for the treatment of VEGF- and mTOR therapy-naïve advanced RCC patients. Also covered are ongoing trials, exploring the efficacy and safety of tivozanib in the setting of refractory disease and the utility of tivozanib in combination with checkpoint inhibitors for advanced RCC. Combination of a VEGFR-TKI and immunotherapy is promising in advanced RCC, if the treatment regimens have acceptable tolerability. Here the selectivity of tivozanib may contribute to an acceptable tolerability profile when used in combination therapy. Expert commentary: The approval of tivozanib provides an additional option for the first-line treatment of advanced or metastatic RCC patients in Europe and allows use of a VEGFR-TKI with selectivity for VEGFRs in this setting
Tumor control outcomes after hypofractionated and single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases from renal cell carcinoma
No full textTo report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors.
PATIENTS AND METHODS:
Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48).
RESULTS:
The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008).
CONCLUSION:
High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking
Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies
No full textBACKGROUND: The most important prognostic factors for survival in patients with metastatic renal cell carcinoma (mRCC) were evaluated in the era of cytokine therapy, and only recently were revalidating in patients receiving targeted therapies (TTs).
METHODS: Clinical data for consecutive patients with mRCC who received TTs were retrieved from the database of Istituto Nazionale dei Tumori of Milan. Variables with a significant association with overall survival (OS) were estimated by proportional hazard regression, and a backward stepwise multivariate analysis identified the independent prognostic factors.
RESULTS: Data for 336 consecutive patients treated with TTs for RCC during the period 2004-2011 were evaluated. According to the Motzer classification, 32% patients were low risk, 48% were intermediate risk and 20% were poor risk. One hundred and sixty-seven (49.7%) patients received one TT, 116 (34.5%) received a second-line TT, 42 (12.5%) a third-line TT and 11 (3.3%) patients received a fourth-line TT. The median OS was 24 months (95% CI 20.0, 27.0) and the 5-year OS rate was 24.6% (95% CI 18.7, 30.8%). In the uni- and multivariate analysis Motzer risk classification, Fuhrman grade and previous cytokine therapy were identified as independent prognostic factors (P<0.01).
CONCLUSION: The Motzer classification was confirmed as an independent prognostic factor for OS in patients with mRCC receiving TTs. Additionally, Fuhrman grade and previous cytokine therapy were independent prognostic factors for clinical outcome
Дополнительное приложение
No full textThis appendix formed part of the original submission and has been peer reviewed.We post it as supplied by the authors. Supplement to: Motzer R, Porta C, Alekseev B, et al. Health-related quality-of-life outcomes in patients with advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab or everolimus versus sunitinib (CLEAR): a randomised, phase 3 study.Lancet Oncol 2022; published online April 27. https://doi.org/10.1016/S1470-2045(22)00212-1.Это приложение было частью первоначального представления и прошло экспертную оценку. Мы публикуем его в том виде, в каком его предоставили авторы.Дополнение к: Motzer R, Porta C, Alekseev B и др. Показатели качества жизни, связанные со здоровьем, у пациентов с прогрессирующей почечно-клеточной карциномой, получавших ленватиниб плюс пембролизумаб или эверолимус в сравнении с сунитинибом (CLEAR): рандомизированное исследование фазы 3. Lancet Oncol 2022; опубликовано в Интернете 27 апреля
Efficacy of Nivolumab plus Ipilimumab According to Number of IMDC Risk Factors in CheckMate 214
No full textIn the randomized, open-label, phase 3 CheckMate 214 trial, nivolumab plus ipilimumab (nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 wk for four doses, then nivolumab 3 mg/kg every 2 wk) had superior efficacy over sunitinib (50 mg once daily, 4 wk on, 2 wk off) in patients with untreated International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate- or poor-risk advanced renal cell carcinoma; the benefits were sustained through extended follow-up. To better characterize the association between outcomes and IMDC risk in CheckMate 214, we completed a post hoc analysis (n = 1051) of efficacy by the number of IMDC risk factors. The investigator-assessed objective response rate (ORR), overall survival (OS), and investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors v1.1 were evaluated. ORR with nivolumab plus ipilimumab was consistent across zero to six IMDC risk factors, whereas with sunitinib it decreased with increasing number of risk factors. Benefits of nivolumab plus ipilimumab over sunitinib in terms of ORR (40-44% vs 16-38%), OS (hazard ratio [HR] 0.50-0.72), and PFS (HR 0.44-0.86) were consistently observed in subgroups with one, two, three, or four to six IMDC risk factors (p < 0.05 for treatment × no. of risk factors interaction). These results demonstrate the benefit of first-line nivolumab plus ipilimumab over sunitinib across all intermediate-risk and poor-risk groups, regardless of the number of IMDC risk factors. PATIENT SUMMARY: This report from the CheckMate 214 study describes a consistent efficacy benefit with first-line nivolumab plus ipilimumab over first-line sunitinib in all groups of patients with intermediate-risk or poor-risk advanced renal cell carcinoma, regardless of the number of risk factors they had before starting treatment. We conclude that there is a benefit of first-line treatment with nivolumab plus ipilimumab for all intermediate-risk patients, including those with one or two risk factors, and for all poor-risk patients, independent of the number of risk factors
Treatment of patients with relapsed and resistant non-Hodgkin's lymphoma using total body irradiation, etoposide, and cyclophosphamide and autologous bone marrow transplantation.
No full textPre-treatment neutrophil to lymphocyte ratio as an independent prognostic factor in patients with treated with everolimus for metastatic renal cell carcinoma
No full textBACKGROUND:
Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the outcome of patients treated with everolimus for mRCC.
METHODS:
Ninety-seven patients with mRCC were treated with everolimus till April 2013 in our institutions. Patients were stratified in two groups with NLR >3 (Group A) vs <3 (Group B). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Gender, age, Motzer prognostic group, PFS on first-line therapy, neutrophilia and NLR were included in the Cox analysis to investigate their prognostic relevance.
RESULTS:
Median OS and PFS were 10.6 and 5.3 months, respectively. Median OS was 12.2 months in Group A and 24.4 months in Group B (P=0.001). Median PFS was 3.4 months in Group A and 9.9 months in Group B (P<0.001). At multivariate analysis, only Motzer prognostic group and NLR were independent prognostic factors for OS and PFS.
CONCLUSION:
Pre-treatment NLR is an independent prognostic factor for patients with mRCC treated with second- or third-line everolimus. This should be investigated and validated in prospective studie
Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma
No full textBackground: Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to >= 6 yr. Objective: To analyze long-term safety with sunitinib in mRCC patients. Design, setting, and participants: Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g. cytokine refractory or treatment-naive). Outcome measurements and statistical analysis: Interval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (>= 2 yr) sunitinib treatment. Results and limitations: Among long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0-= 3 TRAE profiles (<5% difference in incidence rates at all intervals). Limitations included retrospective design, assessment variability, lack of pharmacokinetic data, and absence of baseline characteristics for long-term patients. Conclusions: Prolonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative. Patient summary: More than 800 mRCC patients received sunitinib for between 2 and 6 yr without experiencing new or more severe treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib treatment for as long as patients continue to derive clinical benefit, without untoward additional risk. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved
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