Is there any prognostic importance of pretreatment serum M30 and serum M65 levels on progression-free survival of patients with metastatic renal cell carcinoma treated with first-line sunitinib?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15569-e15569
Author(s):  
Mert Basaran ◽  
Ibrahim Yildiz ◽  
Fatma Sen ◽  
Leyla Kilic ◽  
Serkan Keskin ◽  
...  
Keyword(s):  
Cell Death ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Tumor Cell Death ◽  
First Line ◽  
Free Survival ◽  
Median Serum ◽  
Metastatic Rcc

e15569 Background: Effective cancer biomarkers for early detection, prognosis, or prediction of therapy response are urgently need in metastatic renal cell cancer (RCC). Soluble cytokeratin 18 fragments (M30, M65) are released from human cancer cells during epitelial cell death. Specific enzyme-linked immunosorbent assays (ELISA) using related antibodies distinguish between apoptotic (M30) or apoptotic and necrotic (M65) tumor cell death in serum samples. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates of patients with metastatic RCC treated with first-line sunitinib. Methods: Thirty-nine patients with metastatic RCC and 39 healthy controls were included in this study. The patients’ samples were collected prior to the first cycle of sunitinib therapy and serum M30 and M65 levels were measured by ELISA. Results: The median ages of the patients and controls were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and controls (53.7 vs. 49.1 U/l, P = 0.31). The median serum M65 level was significantly higher in patients than in controls (334.0 vs. 179.1 U/l, P<0.001). Receiver operating characteristic (ROC) analysis revealed that the best cut-off value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/l. The median PFS of patients whose M65 levels were lower than or equal to 313.6 U/l was better than that of patients whose M65 levels were greater than 313.6 U/l (P = 0.03) in univariate analysis. But serum M65 levels in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. Conclusions: Serum M65 levels were significantly elevated in patients with metastatic RCC compared to healthy individuals. Future prospective studies with large sample sizes are needed to address the possible impact of M30 and M65 levels on the treatment responses of patients and whether these markers may be prognostic factors for PFS or OS in patients with RCC.

An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the ‘Pamerit’ study

2020 ◽  
Author(s):  
Alessandra Mosca ◽  
Ugo De Giorgi ◽  
Giuseppe Procopio ◽  
Umberto Basso ◽  
Giacomo Cartenì ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Renal Cell Cancer ◽  
Real World ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Metastatic Renal Cell Cancer ◽  
Metastatic Rcc

Abstract Objective Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Methods Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan–Meier curves, log-rank test and multivariable Cox’s models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Results Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium’s good prognosis (P &lt; 0.001), ECOG PS 0 (P &lt; 0.001), age (&lt;75 years, P = 0.005), surgery (P &lt; 0.001) and response to pazopanib (P &lt; 0.001). After 3 months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium’s favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. Conclusions In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium’s favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium’s good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

Phase II Trial of Weekly Intravenous Gemcitabine With Continuous Infusion Fluorouracil in Patients With Metastatic Renal Cell Cancer

2000 ◽  
Vol 18 (12) ◽  
pp. 2419-2426 ◽  
Author(s):  
Brian I. Rini ◽  
Nicholas J. Vogelzang ◽  
Mary C. Dumas ◽  
James L. Wade ◽  
David A. Taber ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Renal Cell ◽  
Response Rate ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Metastatic Rcc

PURPOSE: To determine the clinical response rate of the combination of weekly intravenous (IV) gemcitabine with continuous infusion fluorouracil (5-FU) in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Between June 1998 and February 1999, 41 patients with metastatic RCC were enrolled onto this multi-institutional phase II study of gemcitabine 600 mg/m2 over 30 minutes on days 1, 8, and 15 and 5-FU 150 mg/m2/d via continuous IV infusion through a permanent catheter on days 1 to 21 of a 28-day cycle. Patients had a Cancer and Leukemia Group B performance status of 0 or 1, with a median time since diagnosis of metastatic disease of 10 months (range, 0 to 129 months). Thirty-three patients (80%) had multiple metastatic sites, and 34 patients (83%) had prior chemotherapy or immunotherapy. RESULTS: Of the 39 assessable patients, there were no complete responses but seven partial responses (objective response rate = 17%; 95% confidence interval, 8% to 34%). Five minor responses (25% to 50% decreased tumor size) were also observed. The duration of response for the seven partial responders was 2, 3, 7, 8, 10, 11, and 14 months. Median progression-free survival for the gemcitabine/5-FU group was 28.7 weeks versus 8 weeks for a similar cohort of patients treated on previous phase II studies at the University of Chicago (P = .008). The regimen was well tolerated, with fatigue, mucositis, nausea/vomiting, and grade 2 hematologic toxicities being most common. CONCLUSION: Weekly gemcitabine with continuous infusion 5-FU is an active combination in patients with metastatic RCC. Therapy was well tolerated and produced an improvement in progression-free survival over historical controls.

Differences in terms of progression-free survival (PFS) and overall survival (OS) in patients treated with first-line sorafenib, sunitinib, and pazopanib for late relapsing (>5 years) renal cell carcinoma.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 421-421
Author(s):  
Matteo Santoni ◽  
Camillo Porta ◽  
Giuseppe Procopio ◽  
Linda Cerbone ◽  
Umberto Basso ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

421 Background: Aim of this retrospective study was to investigate the clinico-pathological features and the outcome of patients (pts) with late relapsing renal cell carcinoma (LateR-RCC) treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) as first line therapy. Methods: Data were collected from 19 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 yr after initial radical nephrectomy. MSKCC prognostic categories were assessed before starting first-line treatment with VEGFR-TKI. Overall survival (OS) and progression free-survival (PFS) were estimated with the Kaplan-Meyer method with 95% CI and curves were compared with log-rank test. A Cox-regression model was applied to the data with a univariate and multivariate approach. Variables included in the univariate analysis were gender, age, time from surgery, MSKCC risk-group and targeted therapy employed at first line. Results: A total of 2,490 pts were screened and 269 pts (11%) were identified as LateR-RCC and treated with first-line VEGFR-TKI. Median age was 66 yr (range 29-87). Median time to recurrence was 7.9 yr. MSKCC prognostic category was good in 63% of pts, intermediate in 31% and poor in 6%. First-line therapy consisted of sunitinib in 190 pts (71%), sorafenib in 58 pts (21%) and pazopanib in 21 pts (8%). The median PFS was 20.0 months (95% CI 17.0−25.1) for sunitinib and 14.1 months for both sorafenib (95% CI 11.0−29.0) and pazopanib (95% CI 11.2−NR). At multivariate analysis, only MSKCC prognostic group was an independent prognostic factor for OS (HR: 2.07; 95% CI, 1.52–2.82 p < 0.001) and PFS (HR 2.54; 95% CI, 1.93−3.36 p < 0.001), whereas first line TKI was not significantly associated with OS (HR: 0.94; 95% CI, 0.38–1.82 p = 0.895) and PFS (HR 0.77; 95% CI, 0.43−1.99 p= 0.547). Conclusions: No significant differences were found in terms of OS and PFS in pts with LateR-RCC treated with first-line sorafenib, sunitinib or pazopanib. Our data may be considered in the long-term management of these patients.

CpG-island methylation of GATA-family members GATA3 and GATA5 in renal cell carcinoma and association with clinicopathological parameters and progression-free survival.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 370-370
Author(s):  
Inga Peters ◽  
Kai Gebauer ◽  
Faranaz Atschekzei ◽  
Joerg Hennenlotter ◽  
Mario W. Kramer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cpg Island ◽  
Cell Cancer ◽  
Family Members ◽  
Progression Free Survival ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Gata Family

370 Background: Transcriptional inactivation and CGI methylation of GATA3 and −5 has been reported to be involved in mammary carcinoma, pancreatic cancer, colorectal and gastric carcinogenesis. A recent study demonstrated that a loss of GATA-3 expression due to partially methylation silencing in several renal cell carcinoma (RCC) patients. We quantitatively investigated GATA3 and −5 CGI methylation in RCC and analyzed its association with clinical characteristics as well as progression free survival of patients. Methods: Methylation data were obtained from a quantitative methylation-specific polymerase chain reaction assay (QMSP) for both genes. We investigated 108 RCC and 77 paired tissue samples as well as six RCC cell lines. Statistical analyses were carried out using the paired t-test for matched tumor (TU) and adjacent normal (adN) samples, logistic regression for comparisons of independent samples and cox regression for survival analysis. Results: In paired samples we found a significant higher methylation in TU compared to adN for GATA3 (P=0.007) and for GATA5 (P=3.6*10−9) for all RCCs. GATA5 showed also strong correlations between methylation and status of metastasis (P=0.05) and advanced (pT≥3 and/or N+, M+) tumor samples compared to localized (pT≤2, N0, M0) tumors (P=4.7*10−9). A decreased progression free survival in cox proportional hazard model analysis could be demonstrated for patients with a high GATA5 methylation (P=0.0006, HR=6.5) and a trend could also be seen for GATA3 methylated patients (P=0.06). Conclusions: GATA3 and −5 were identified to demonstrate tumor-specific CGI hypermethylation in renal cell cancer patients. The association of GATA5 CGI methylation with metastasis, advanced disease and progression free survival of patients indicates that epigenetic alterations of both genes are involved in renal cell carcinogenesis. GATA5 methylation could serve as a biomarker for tumor progression. Further prospective and functional investigations are necessary to clarify whether CGI methylation of GATA family members can provide independent information for future clinical management of patients with RCC.

Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15615-e15615
Author(s):  
Ugo De Giorgi ◽  
Karim Rihawi ◽  
Michele Aieta ◽  
Giovanni Lo Re ◽  
Teodoro Sava ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Elderly Patients ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Metastatic Renal Cell Cancer ◽  
Grade 3

e15615 Background: Lymphopenia is associated with toxicity and outcome in several cancer types. We assessed the association of pre-treatment lymphopenia with toxicity and clinical outcome of elderly patients with metastatic renal cell cancer treated with first-line sunitinib. We evaluated the prognostic factors in these patients. Methods: We reviewed the clinical files of 181 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1,000/µL. Results: Twenty–nine patients (16.0%) had a baseline lymphocyte counts <1,000/µL, and 152 (84%) ≥1,000/µL. No difference between the two groups was reported in overall response rate (p = 0.207), dose reductions (p = 0.740); discontinuations due to adverse events (p = 0.175), overall incidence of grade 3-4 toxicities (p = 0.112) even if more patients in the group with lymphopenia had grade 3-4 neutropenia (p = 0.017), grade 3-4 thrombocytopenia (p = 0.017) and grade 3-4 diarrhea (p = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (p = 0.015 and p = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (p = 0.007, p < 0.0001 and p = 0.023, respectively). Conclusions: Sunitinib appeared safe and active in elderly patients with lymphopenia. Lymphocyte counts is an independent prognostic factor for OS in elderly patients with mRCC treated with first-line sunitinib.

Phase II study of sequential first-line pazopanib (PAZ) followed by everolimus (EVE) in patients (pts) with advanced or metastatic renal cell carcinoma (RCC) (CATChEz Study).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 648-648 ◽  
Author(s):  
Paul L. de Souza ◽  
Shirley Wong ◽  
Sanjeev Sewak ◽  
Dusan Kotasek ◽  
Bhumsuk Keam ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Anticancer Treatment ◽  
Secondary Endpoints ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Metastatic Rcc

648 Background: EVE following failure of sorafenib or sunitinib for RCC was first approved by the FDA in 2009. CATChEz (NCT01545817) was designed to test the activity of EVE following first-line PAZ in pts with advanced or metastatic RCC who had not received prior systemic therapy. Methods: From 2012 to 2016, pts received first-line PAZ followed by EVE until progressive disease (PD), death, unacceptable toxicity, consent withdrawal, or study termination. Pts with PD during or within 6 months of stopping PAZ were eligible for EVE. Pts off study treatment were evaluated for PD, survival, and updates on anticancer treatment every 8 weeks until death or end of study. The primary efficacy endpoint was median progression-free survival (mPFS) for the second-line EVE treatment period; secondary endpoints included other survival measures, and safety evaluations were for second-line EVE and grade 3/4 toxicities attributable to PAZ and EVE. Results: Of 74 pts who started first-line PAZ, 38 received ≥1 dose of second-line EVE. The primary endpoint of mPFS from the start of second-line EVE and the secondary endpoint of mPFS with first-line PAZ (Table) were consistent with previous reports; no unexpected adverse events (AEs) were reported. All pts had ≥1 treatment-emergent AE, 83.8% had grade ≥3 AEs, and 71.6% had serious AEs. Of 34 total deaths, 29 were due to PD and 5 were due to AEs (2 related to EVE [lower respiratory tract infection; pulmonary sepsis]; 3 unrelated to study treatment). Conclusions: Efficacy and safety outcomes were consistent with published phase III data. The CATChEz study supports sequential first-line use of PAZ followed by EVE for the treatment of pts with advanced or metastatic RCC. Clinical trial information: NCT01545817. [Table: see text]

A new modified sunitinib schedule for metastatic renal cell cancer (mRCC): A pilot study.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 471-471
Author(s):  
Sebastiano Buti ◽  
Maddalena Donini ◽  
Silvia Lazzarelli ◽  
Matteo Brighenti ◽  
Rodolfo Passalacqua
Keyword(s):  
Pilot Study ◽  
Meta Analysis ◽  
Cell Cancer ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
First Line ◽  
Treatment Delays ◽  
Free Survival ◽  
Dose Reductions ◽  
Modified Schedule

471 Background: Oral sunitinib administration at 50 mg daily given for 4 weeks followed by 2 weeks off treatment (4+2 schedule) is a standard first line for mRCC treatment. About 20% of patients had to discontinue treatment permanently and 50% of patients are forced to reduce the doses due to adverse events [Motzer RJ, J Clin Oncol. 2009]. A meta-analysis showed that increase exposure to sunitinib is associated with improved clinical outcome [Houk BE, Cancer Chemother Pharmacol. 2010]. Methods: This is a pilot study in which consecutive mRCC patients admitted to our hospital who had at least a grade 2 toxicity with sunitinib, were switched to a modified schedule maintaining the same dose-intensity of 4+2 schedule: starting on Monday, 1 tablet (50 mg) a day for 5 consecutive days a week for 5 weeks and 1 tablet per day on days 1, 3 and 5 in the sixth week (28 tablets in 6 weeks), until disease progression. Primary end points were toxicity changes assessment and schedule feasibility, secondary end point was overall progression free survival (PFS). Results: Eight nephrectomized patient were enrolled: 6 males; median age 61; 37% good, 50% intermediate and 13% poor MSKCC risk; 3 patient pretreated; 6 clear cell histologies, 1 papillary and 1 undifferentiated histotypes. Median time from start therapy to switch was 7.4 months (range 1.4-16.1). Treatment delays and dose reductions were reduced from 50% to 25% and from 37% to 12% of patients respectively. The table shows the toxicity changes: there were no new toxicities. PFS was 16.3 months (CI 95% 5.6-23.4). Conclusions: This new modified schedule requires and deserves further studies. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document