Research Interests: Clinical Trial, Medicine, Population, Humans, Internal Medicine, and 15 moreFemale, Male, Aged, Middle Aged, Benchmarks, Outcomes Assessment, Antineoplastic Agents, Molecular Targeted Therapy, Overall Survival, Proportional Hazards Models, Progression Free Survival, Clinical Trials as Topic, Disease Free Survival, Neoplasm metastasis, and Metastatic Renal Cell Carcinoma
Nude mice bearing s.c. xenografts of the human colon adenocarcinoma HT29 were given intratumor injections of a mixture of 125I-labeled specific antibody (AUA1) and 131I-labeled control antibody (HMFG1), or with the labels reversed. After... more
Nude mice bearing s.c. xenografts of the human colon adenocarcinoma HT29 were given intratumor injections of a mixture of 125I-labeled specific antibody (AUA1) and 131I-labeled control antibody (HMFG1), or with the labels reversed. After dissection at 1 and 4 h postadministration, both specific and control antibodies had 47-63% of the injected dose (% ID) in the tumor. By 24 h, the tumor contained 43 +/- 11% ID of AUA1 which persisted at around this level for 5 days and remained at nearly 20% ID at 18 days. In contrast, the HMFG1 activity was 23 +/- 9% ID at 24 h, which continued to fall and was less than 5% ID by 7 days. Normal organ levels were less than 2% ID/g for both antibodies, with HMFG1 being higher than AUA1 at all times, resulting in specificity indices greater than 20 by 5 days. Autoradiography of tumors removed 2 h postinjection of 125I-labeled AUA1 or HMFG1 showed high levels of antibody at the injection site. At 48 h and 7 days postinjection, the specific antibody was...
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Purpose: The cellular inhibitor of apoptosis protein (cIAP) is regarded as an important prognostic biomarker in cancer. Here, we sought to determine the prognostic value of cIAP protein levels in epithelial ovarian cancer using a novel... more
Purpose: The cellular inhibitor of apoptosis protein (cIAP) is regarded as an important prognostic biomarker in cancer. Here, we sought to determine the prognostic value of cIAP protein levels in epithelial ovarian cancer using a novel method of compartmentalized in situ protein analysis. Methods: A tissue array composed of 150 advanced-stage ovarian cancers, treated with surgical debulking followed by platinum/paclitaxel–based combination chemotherapy, was constructed. For evaluation of protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis. Results: The mean follow-up time for the entire cohort was 34.4 months. Patients with tumors bearing high cIAP membranous expression had a 3-year survival rate of 31% compared with 73% for patients with low cIAP expressing tumors (P = 0.0020). In multivariable analysis, adjusting for well-characterized prognostic variables, low membranous cIAP expression level was the onl...
Research Interests: Oncology, Cancer, Biology, Ovarian Cancer, Medicine, and 15 moreHumans, Internal Medicine, Automation, Female, Paclitaxel, Biomarker, Survival Rate, Prognosis, Cohort Studies, Combined Modality Therapy, Inhibitor of apoptosis proteins, epithelial ovarian cancer, Neoplasm staging, Medical and Health Sciences, and Ovarian Neoplasms
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430 Background: Third-line targeted therapy efficacy in metastatic renal cell carcinoma (mRCC) is not well characterized and many funding bodies do not provide reimbursement for it. Methods: The International mRCC Database Consortium... more
430 Background: Third-line targeted therapy efficacy in metastatic renal cell carcinoma (mRCC) is not well characterized and many funding bodies do not provide reimbursement for it. Methods: The International mRCC Database Consortium (IMDC) consists of consecutive patient series from 25 cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival. Cox proportional hazards models were used to adjust hazard ratios for confounders. Patients that stopped second-line therapy were divided into two groups: those that went onto third-line therapy and those did not. Results: 4,050 patients were treated with first-line targeted therapy, of which 2,011 (49.6%) had second-line therapy and 879 (21.7%) had third-line targeted therapy. The most common third-line therapies were everolimus 25%, sorafenib 14%, sunitinib 13%, temsirolimus 11%, pazopanib 10%, and axitinib 6%. IMDC prognostic groups at third-line therapy initiation were 6% favorable risk, 67% intermediate risk, and 27% poor risk. Overall response rate for third-line therapy was 10.5% and 50.9% had stable disease in those patients that were evaluable. Median PFS was 5.1 months (95% CI, 4.5-5.7) and median OS from third-line therapy initiation was 12.0 months (95% CI, 10.7-12.9). Patients stopping second-line therapy that move on to third-line therapy vs. those that do not receive third line therapy have a median OS from stopping second-line therapy of 13.1 vs. 2.3 mons (p<0.0001). When adjusted for second-line IMDC prognostic criteria and KPS at second-line treatment cessation, patients who do receive third-line therapy have a HR of death of 0.41 (95% CI, 0.32-0.52; p<0.0001) compared to those that do not receive third-line therapy. This may be in part due to patient selection. To further limit bias, when excluding patients that live less than 3 months after second-line therapy cessation, the adjusted HR was similar. Conclusions: Third-line targeted therapy has demonstrated activity and is prevalent in use. Further studies are required to determine appropriate sequencing.
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Background/aim: Easily assessable clinical predictors of response to chemotherapy in advanced castration-resistant prostate cancer (CRPC) are few. The objective of this retrospective study was to search for and identify such candidate... more
Background/aim: Easily assessable clinical predictors of response to chemotherapy in advanced castration-resistant prostate cancer (CRPC) are few. The objective of this retrospective study was to search for and identify such candidate predictors of outcome. Patients and methods: A retrospective analysis of clinical data of CRPC patients entered in the Clinical Therapeutics' departmental prostate cancer database from 1996-2009 was performed. Univariate and multivariate analyses for progression-free survival and overall survival included patients receiving both docetaxel- and non-docetaxel-containing regimens. Results: From 1996 until June 2009, 286 out of 313 patients in our database were treated with chemotherapy. Prostate-specific antigen (PSA) reduction >30% correlated with improved survival irrespective of treatment. Beyond previously reported predictors, i.e. baseline PSA >30 ng/dl, hemoglobin below 10 mg/dl, weight loss, poor performance status, elevated lactic dehydrogenase and alkaline phosphatase, and time to CRPC of less than or equal to two years was associated with a poor overall survival and shorter progression-free survival upon univariate analysis. Pain was associated with shorter survival. Multivariate analysis confirmed time to CRPC, lactate dehydrogenase and alkaline phosphatase as independent predictors of overall and progression-free survival. Conclusion: Time to castration resistance is an important predictor of outcome in CRPC. PSA reduction >30% predicts survival improvement following chemotherapy for CRPC regardless of chemotherapy applied.
Research Interests: Oncology, Pain, Treatment Outcome, Prostate Cancer, Medicine, and 15 moreHumans, Internal Medicine, Female, Pubmed, Male, Anticancer, Aged, Time Factors, Retrospective Studies, Prostate Specific Antigen, Antineoplastic Agents, Docetaxel, Combined Modality Therapy, Prostatic neoplasms, and orchiectomy
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Background:Several ongoing phase 2 trials are evaluating new neoadjuvant therapy regimens in patients with muscle-invasive bladder cancer (MIBC). The 1-yr recurrence-free survival (RFS) after radical cystectomy (RC), with or without... more
Background:Several ongoing phase 2 trials are evaluating new neoadjuvant therapy regimens in patients with muscle-invasive bladder cancer (MIBC). The 1-yr recurrence-free survival (RFS) after radical cystectomy (RC), with or without perioperative chemotherapy, can be used to model statistical assumptions and interpret outcomes from these studies.Objective:To provide a benchmark for predicting 1-yr RFS in patients with cT2–4N0 MIBC.Design, setting, and participants:We identified 950 patients with clinical stage T2–4N0 MIBC undergoing RC at 27 centers between 1990 and 2016. We assessed 1-yr RFS rates for patients managed with no perioperative chemotherapy, neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), or NAC followed by AC. Cox regression analyses tested for 1-yr postsurgical RFS predictors. A Cox-based nomogram was developed to estimate 1-yr RFS and its accuracy was assessed in terms of Harrell’s c-index, a calibration plot, and decision curve analysis. We report 1-yr RFS rates across the nomogram tertiles.Results and limitations:The 1-yr RFS rates were 67.9% (95% confidence interval [CI] 64–72) after no perioperative chemotherapy, 76.9% (95% CI 72–83%) after NAC, 77.8% (95% CI 71–85%) after AC, and 57% (95% CI 37–87) after NAC + AC. On multivariable analysis, positive surgical margins (p = 0.002), pT stage (p < 0.0001), and pN stage (p<.0001) were significantly associated with RFS, while NAC was not (p = 0.6). The model including all these factors yielded a c-index of 0.76 (95% CI 0.72–0.79), good calibration, and a high net benefit. The 1-yr RFS rates across nomogram tertiles were 90.5% (95% CI 87–94%), 73.4% (95% CI 68–79%), and 51.1% (95% CI 45–58%), respectively. The results lack external validation.Conclusions:Benchmark 1-yr RFS estimates for phase 2 design of new neoadjuvant trials are proposed and can be used for statistical assumptions, pending external validation.Patient summary:Our prognostic model predicting 1-yr survival free from recurrence of bladder cancer after radical cystectomy, with or without standard chemotherapy, could provide an improvement to the quality of phase 2 clinical trial designs and interpretation of their results.
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Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs) have been associated with prognosis in ovarian cancer, but their prognostic significance in ascites has not been studied. We performed a prospective study of T... more
Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs) have been associated with prognosis in ovarian cancer, but their prognostic significance in ascites has not been studied. We performed a prospective study of T lymphocytes isolated from ascites from patients with ovarian carcinoma and we compared them with the respective populations in blood and tumors. Mononuclear cells from ascites (n=71) and blood were isolated by Ficoll, while tumor lymphocytes (n=20) were obtained upon mechanical dissociation. Phenotypic analysis was performed with flow cytometry. Ascites from 10 patients with cirrhosis was used as control. Tregs containing CD4(+)CD25(+) cells, NK-T containing CD3(+)CD56(+) cells and CD69 and HLADR expression of CD4 and CD8 lymphocytes were significantly increased in tumor ascites compared to blood and control ascites. A selective accumulation of these populations in the ascites of cancer patients, was suggested by the significantly higher ascites/blood (A/B) ratios in cancer patients but not controls. Cancer cell content in ascites was correlated with CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)HLADR(+) and CD8(+)CD69(+) cells. There was no correlation of lymphocyte populations between ascites and samples from peritoneal metastases. Higher tumor grade was associated with increased A/B CD4(+)CD25(+) ratio and reduced CD3(+)CD56(+) cells, while platinum resistance was associated with reduced A/B CD3(+)CD56(+) ratio. There are significant differences of CD3(+)CD56(+) and CD25(+)CD4(+) lymphocytes and increase in lymphocyte activation between blood, ascites and peritoneal metastases from patients with ovarian cancer. The selective accumulation of CD3(+)CD56(+) population in ascites may be a predictive factor for platinum resistance.
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e15040 Background: The use of tyrosine kinase inhibitors (TKIs) in mRCC has improved prognosis but the individual outcome remains largely unpredictable. The MSKCC model, used to identify risk groups, was developed in cytokine-treated... more
e15040 Background: The use of tyrosine kinase inhibitors (TKIs) in mRCC has improved prognosis but the individual outcome remains largely unpredictable. The MSKCC model, used to identify risk groups, was developed in cytokine-treated patients and has not been externally validated in the TKI era. It contains 3 laboratory factors (total 5), making its application to retrospective series somewhat problematic. Subsequently, a more complicated model, using 4 laboratory factors (total 6) has been described. The Hellenic Cooperative Oncology Group recently described a simpler model with only 3 clinical factors. We are describing the application and external validation of this model. Methods: 128 Greek patients with mRCC treated with 1st line sunitinib were included. All had had nephrectomy. Previous interferon was allowed. Cox regression was used to develop a predictive model for overall survival (OS). Our model was compared to that of MSKCC and Heng’s using ROC curves and Harrell’s Concordance Index. Risk groups were defined by the calculated prognostic index and by clinical factors. External validation was done using a sample of 226 French patients. The Royston and Sauerbrei D statistic was used as a measure of discrimination of the survival model. Results: Time from diagnosis of RCC to start of sunitinib (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;12), PS (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1) and number of metastatic sites (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1) were independent adverse prognostic factors in the Greek dataset. The co-efficients for each factor were: 0.51, 0.97, 0.61, respectively. The 3 risk groups were defined by the 25th and 75th percentiles of the prognostic index values (Table 1). The model was of equal prognostic value to the MSKCC (p=.272) and Heng’s (p=.075). French had better survival than Greek patients especially in the high risk group (for all models). Validation of our model in the French data showed that it was applicable (R2 D: 0.14, SE: 0.09), especially for the low/medium risk groups. Conclusions: Our model is the only one externally validated in TKI-treated patients. It may be considered as a simpler alternative to those currently applied. [Table: see text]
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Background: Members of the α-thymosin family have long been studied for their immunostimulating properties. Among them, the danger-associated molecular patterns (DAMPs) prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109)... more
Background: Members of the α-thymosin family have long been studied for their immunostimulating properties. Among them, the danger-associated molecular patterns (DAMPs) prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) have been shown to act as immunomodulators in vitro, due to their ability to promote T helper type 1 (Th1) responses. Recently, we verified these findings in vivo, showing that both proTα and proTα(100-109) enhance antitumor-reactive T cell-mediated responses. Methods: In view of the eventual use of proTα and proTα(100-109) in humans, we investigated their safety profile in silico, in human leukocytes and cancer cell lines in vitro, and in immunocompetent mice in vivo, in comparison to the proTα derivative thymosin alpha 1 (Τα1), a 28-mer peptide extensively studied for its safety in clinical trials. Results: In silico prediction via computational tools showed that all three peptide sequences likely are non-toxic or do not induce allergic regions. In...
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Sunitinib is approved for the treatment of metastatic renal cell carcinoma (RCC). No data are available on sunitinib use specifically in patients with significantly impaired renal function. We evaluated the safety and efficacy of... more
Sunitinib is approved for the treatment of metastatic renal cell carcinoma (RCC). No data are available on sunitinib use specifically in patients with significantly impaired renal function. We evaluated the safety and efficacy of sunitinib in patients with advanced RCC and Grade 4 renal function impairment. Four patients had a calculated creatinine clearance of 15 - 29 ml/min/1.73 m2 prior to initiation of sunitinib. Three patients tolerated treatment well with no renal toxicity: 2 received 17 and 5 cycles of sunitinib at full dose, while 1 received 5 cycles with a dose reduction due to myelotoxicity. We observed one partial response and two patients had stable disease for 24 and 4 months, respectively. The 4th patient had a creatinine clearance of 18 ml/min/1.73 m2 and had treatment discontinued during the first cycle due to poorly controlled hypertension and deterioration of his renal function. We conclude that sunitinib can be administered to the majority of patients with RCC and significant renal function impairment.
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396 Background: The role of cytoreductive nephrectomy is unclear in patients with synchronous metastases from renal cell carcinoma (RCC) in the age of targeted therapy. Methods: Comparisons were made between patients treated with targeted... more
396 Background: The role of cytoreductive nephrectomy is unclear in patients with synchronous metastases from renal cell carcinoma (RCC) in the age of targeted therapy. Methods: Comparisons were made between patients treated with targeted therapy who had a CN versus not and adjusted using proportional hazards regression for known poor prognostic criteria (IMDC criteria Heng et al JCO 2009). Results: 2569/3245 (79%) mRCC patients received a nephrectomy. Patients who had nephrectomy before the diagnosis of metastatic disease were excluded (n=1634). Among the remaining patients, 935 patients had a CN and 676 patients did not have nephrectomy. All patients received targeted therapy with the majority receiving first-line sunitinib 72%, sorafenib 15%, temsirolimus 5%, bevacizumab 3%, pazopanib 3%. Patients who had CN had better IMDC prognostic profiles versus those without (favorable/intermediate/poor in 9%/63%/28% vs 1%/45%/54% p&amp;amp;amp;lt;0.0001). The median overall survival of patients with CN vs without was 20.6 vs 9.5 months (p&amp;amp;amp;lt;0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95%CI 0.52-0.69, p&amp;amp;amp;lt;0.0001). The Table demonstrates the increasing benefit of CN if a given patient has a longer survival time. Conclusions: CN can be beneficial in patients with synchronous metastatic RCC even after adjustment for prognostic factors. Patients who are estimated to survive less than 9-12 months may have a marginal benefit compared to those with longer estimated survival. This may aid in patient selection as we await results from randomized controlled trials. [Table: see text]
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544 Background: Sunitinib (SU) and Pazopanib (PZ) have been compared head-to-head in the first-line phase III COMPARZ study in metastatic renal cell carcinoma (mRCC). We compared SU versus PZ, to confirm outcomes and subsequent... more
544 Background: Sunitinib (SU) and Pazopanib (PZ) have been compared head-to-head in the first-line phase III COMPARZ study in metastatic renal cell carcinoma (mRCC). We compared SU versus PZ, to confirm outcomes and subsequent second-line therapy efficacy in a population-based setting. Methods: We used the IMDC to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS2 and PFS2 were also evaluated. Results: We obtained data from 3,606 patients with mRCC treated with either first line SU (n=3226) or PZ (n=380) with an overall median follow-up of 43.5 months (m) (CI95% 41.4 – 46.4). IMDC risk group distribution for favorable prognosis was 440 (17.3%) for SU vs 72 (25%) for PZ, intermediate prognosis 1414 (55.6%) for SU vs 153 (53%) for PZ, poor prognosis 689 (27.1%) for SU vs 62 (22%) for PZ, p= 0.0027. We found no difference between SU vs. PZ for OS (20.1 [CI95% 18.76-21.42] vs. 23.68 m [CI95% 19.54 - 28.81] p=0.19), PFS (7.22 [CI95% 6.76 - 7.78] vs. 6.83 m [CI95% 5.58 - 8.27] p=0.49). The RR was similar in both groups (Table 1). Adjusted HR for OS and PFS were 0.952 (CI95% 0.788 – 1.150 p=0.61) and 1.052 (CI95% 0.908 – 1.220 p = 0.49), respectively. We also found no difference in any second-line treatment between either post-SU vs. post-PZ groups for OS2 (12.88 [CI95% 11.89 – 14.19] vs. 12.91 m [CI95% 10.3 – 19.1] p=0.47) and PFS2 (3.67 [CI95% 3.38 – 3.87] vs. 4.53 m [CI95% 3.08 – 5.35] p=0.4). There was no statistical difference in OS2 and PFS2 if everolimus was used after SU or PZ (p = 0.33 and p = 0.41, respectively) or if axitinib was used after SU or PZ (p = 0.73 and p = 0.72, respectively). Conclusions: We confirmed in real world practice, that SU and PZ have similar efficacy in the first-line setting for mRCC and do not affect outcomes with subsequent second-line treatment. [Table: see text]
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Tumour-associated lymphocytes (TALs) present in effusions of ovarian cancer patients exhibit impaired activities, due to the immunosuppressive environment of the ascites. Means to enhance their cytotoxicity against autologous tumour cells... more
Tumour-associated lymphocytes (TALs) present in effusions of ovarian cancer patients exhibit impaired activities, due to the immunosuppressive environment of the ascites. Means to enhance their cytotoxicity against autologous tumour cells are of clinical importance. The immunomodulator prothymosin alpha (proTα) increases the specific lysis of tumour cells by activated CD8(+) T-lymphocytes and its immunoreactivity is exerted by the carboxy-terminal decapeptide, proTα(100-109). These two molecules were studied on TALs in vitro, and in SCID mice bearing human ovarian tumours. TALs and tumour cells were isolated from 41 ovarian cancer patients and co-cultured in the presence of proTα or proTα(100-109). The cytotoxicity of peptide-stimulated TALs was tested against autologous tumour cells and K562. Ex vivo peptide-stimulated TALs from three patients were adoptively transferred intraperitoneally in SCID mice, previously inoculated with each patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s autologous tumour cells. ProTα and its immunoreactive peptide proTα(100-109), enhanced the cytotoxic activity of TALs against autologous tumour cells in vitro, but marginally affected the lysis of K562. The effect of proTα and proTα(100-109) was higher after 7-14 days of stimulation, whereas TAL cytotoxicity was significantly decreased after 21 days. Mice administered TALs, ex vivo activated with proTα or proTα(100-109) for 7 days, showed a relatively lower tumour increase rate and a prolongation of their survival, compared to controls. Our data demonstrate that, in the presence of tumour antigens, proTα and proTα(100-109) enhance the depressed cytotoxicity of TALs against autologous tumour cells in vitro and retard tumour growth in vivo.
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The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in... more
The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population. To evaluate the use and efficacy of targeted therapy in a third-line setting. Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis. Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status. Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study. TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS. Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated longer overall survival compared with those with poor risk disease.
Research Interests: Oncology, Survival Analysis, Risk assessment, Medicine, Humans, and 15 moreInternal Medicine, Female, Renal cell Carcinoma, Male, Everolimus, Clinical Sciences, Internationality, Retrospective Studies, Targeted Therapy, Risk Assessment, Sorafenib, Antineoplastic Agents, Sunitinib, Axitinib, and pazopanib
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e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline... more
e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline characteristics and treatment outcomes in African-Americans (AA) and Hispanic patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Caucasians, AA and Hispanics with mRCC treated with 1stline VEGF-TT were identified from the IMDC. We created 2 matched cohorts: 1) AA vs. Caucasians and 2) Hispanics vs. Caucasians, both matched for age (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50; 50-59; 60-69; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;70-year-old), gender, years of treatment (2003-07; 2008-12; 2013-16) and geography (Canada, USA, Europe). Weighted Cox and logistic regressions were used to compare OS, time-to-treatment failure (TTF) and best response, adjusted for nephrectomy status, IMDC risk groups, number of metastatic sites (1 v. &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1) and histology (clear-cell vs. else). Results: 73 AA and 71 Hispanics met eligibility criteria and were matched with 1236 and 901 eligible Caucasians, respectively. AA had more non-clear cell histology (26% v. 11%), time from diagnosis to therapy&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 year (67% v. 55%) and anemia (75% v. 54%) vs. Caucasians. Differences were not significant for Hispanics. Clinical outcomes are presented in Table. Conclusions: Adjusted for clinical prognostic factors, Hispanics with mRCC have statistically shorter TTF and survival than Caucasians. AA had a trend toward shorter TTF (not significant) but similar survival than Caucasians. Underlying genetic/biological differences, along with potential cultural variations, may impact survival in Hispanic mRCC patients. [Table: see text]
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e15552 Background: The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by down-regulating dendritic cell... more
e15552 Background: The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by down-regulating dendritic cell maturation and thus T cell activation. We investigated the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. METHODS Circulating T cells from healthy donors (n=9) and ovarian cancer patients (n=5) were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity against K562 and Daudi cell lines, in a standard 4-h 51Cr-release assay, and the expression of VEGFRs 1, 2, and 3 was assayed by flow cytometry, immunocytochemistry, and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by ELISA. RESULTS The addition of VEGF in cultures showed that concentrations above 1 ng/ml significantly reduced T cell proliferation (p=0.043 for comaprison with controls). The suppressive effect was dose-dependent from 1 to 10 ng/ml, after which there was a plateau of the inhibitory effect. Protein expression studies demonstrated that CD3+ T cells express VEGFR-2 on their surface upon activation. The direct suppressive effect of VEGF on T cell proliferation was reversed by anti-VEGFR-2 antibodies. This finding proves that the suppressive effect of VEGF on T cells is mediated by VEGFR-2. We also showed that VEGF at 5 ng/ml significantly reduced the cytotoxic activity of T cells against K562 and Daudi cells (p=0.042 for comparison with controls). Activated T cells secreted VEGF in the culture environment (mean value: 192 pg/ml). Nevertheless, these levels are well below those necessary to produce T cell suppression in culture (1 ng/ml). CONCLUSIONS This study shows that VEGF directly suppresses T cell activation via VEGF receptor type 2. The levels shown to produce suppression in vitro (>= 1 ng/ml) are in concert to the level of VEGF in ascites, which predicted for a poor outcome (1.9 ng/ml) in a previous study (Bamias et al, Gynecol Oncol 2008).
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Research Interests: Chemotherapy, Colorectal cancer, Greece, Humans, Internal Medicine, and 15 moreFemale, Male, IT Value, Aged, Adult, Colon cancer, Camptothecin, Antineoplastic Agents, Adjuvant Chemotherapy, Irinotecan, Leucovorin, Disease Free Survival, fluorouracil, Medical and Health Sciences, and Colonic Neoplasms
398 Background: Prior prognostic models for 2nd-line systemic therapy have not been studied in the setting of contemporary sequential targeted therapy (TT). We sought to validate the IMDC prognostic model in patients with mRCC receiving... more
398 Background: Prior prognostic models for 2nd-line systemic therapy have not been studied in the setting of contemporary sequential targeted therapy (TT). We sought to validate the IMDC prognostic model in patients with mRCC receiving next-line TT after progression on 1st-line TT. Methods: Patients who received 2nd-line TT after progressing on 1st-line TT for mRCC at 19 centres were analyzed. For the patients who had immunotherapy (22%) prior to their 1st TT, we examined their second TT (ie 3rd-line therapy). The endpoint was median overall survival (OS) since the initiation of 2nd-line therapy. Additionally, we compared the IMDC model with the 3-factor-MSKCC model (Motzer et al JCO 2004) used for previously-treated patients. Results: 1,021 patients treated with a second TT were included. Median time on 2nd-line TT was 3.9 months (range 0-76+). 871 (85%) of patients had stopped 2nd-line TT by the time of analysis. Median OS since 2nd-line TT was 12.5 months (95% CI: 11.3-14.3 months), with 369 (36.1%) of patients remaining alive. 5 out of 6 pre-defined factors in IMDC model (anemia, thrombocytosis, neutrophilia, KPS &amp;amp;amp;lt;80%, and &amp;amp;amp;lt;1 year from diagnosis to treatment) measured at the time of 2nd-line TT were independent predictors of poorer OS (HR between 1.39 and 1.58, p&amp;amp;amp;lt;0.05). Hypercalcemia was not statistically significant in multivariable analysis (p=0.3008) likely due to the low incidence of hypercalcemia (9%). The concordance index using all 6 prognostic factors was 0.70, and was 0.66 with the 3-factor-MSKCC model. When patients were divided into 3 risk categories using IMDC criteria, median OS was 35.8 months (95% CI 28.3-47.8) in the favorable risk group (n=76), 16.6 months (95% CI 14.9-17.9) in the intermediate risk group (n=529), and 5.4 months (95% CI 4.7-6.8) in the poor risk group (n=261). Conclusions: The IMDC prognostic model has been validated in and can be applied to patients previously treated with TT, in addition to previously validated populations in 1st-line TT and non-clear cell setting.
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14558 Background: Cisplatin-based chemotherapy represents the standard for patients with inoperable or recurrent urothelial carcinoma. Carboplatin-based chemotherapy is reserved for not-fit-for-cisplatin patients. Recent data suggest that... more
14558 Background: Cisplatin-based chemotherapy represents the standard for patients with inoperable or recurrent urothelial carcinoma. Carboplatin-based chemotherapy is reserved for not-fit-for-cisplatin patients. Recent data suggest that carboplatin-based chemotherapy may be effective in fit-for-cisplatin patients. We examined the differences in the outcome according to the compound used as first-line treatment. Methods: We selected patients who received first-line combination chemotherapy based on cisplatin or carboplatin. The major end point was survival. Survival curves were estimated with the Kaplan-Meier method, while cox regression analysis was used for multivariate models. Results: 445 patients, treated with cisplatin (330) or carboplatin (115)-based chemotherapy were included in this analysis. After a median follow-up of 52 months, there was no significant difference in survival between the two treatment groups (Table). Subgroup analyses according to PS, distant metastases, Hb, weight loss, showed that the use of cisplatin was independently associated with improved survival only in the PS 2,3 subgroup (see Table). When patients were stratified according to the Bajorin prognostic criteria (PS 0,1 vs. 2,3 and/or distant metastases yes vs. no; J Clin Oncol 1999, 17: 3173), again cisplatin-based chemotherapy was associated with a trend towards improved outcome only in the worst prognostic group (Table). Conclusions: Carboplatin-based chemotherapy may be equally effective to cisplatin-based treatment in patients with inoperable or recurrent urothelial cancer and no or one adverse factors. Cisplatin-based treatment may be beneficial in patients with poor prognosis. Nevertheless, the clinical relevance of this superiority is limited due to the poor outcome and the poor tolerance of cisplatin-based combination chemotherapy in this group of patients. (see Table) Median survival (95% CI) after first-line chemotherapy for advanced urothelial carcinoma. [Table: see text] No significant financial relationships to disclose.
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Serum CD105 has been associated with angiogenic activity in cancer, and low CD105 expression has been associated with improved prognosis. The present study evaluated the prognostic significance of serum levels of CD105 and related factors... more
Serum CD105 has been associated with angiogenic activity in cancer, and low CD105 expression has been associated with improved prognosis. The present study evaluated the prognostic significance of serum levels of CD105 and related factors in patients with epithelial ovarian cancer (EOC) after cytoreductive surgery and chemotherapy. Eighty-six patients with stages IIC to IV EOC treated postoperatively with platinum-based chemotherapy were included. The enzyme-linked immunosorbent assay was used to measure prechemotherapy serum levels of CD105, transforming growth factor beta1/2 (TGF-beta1/2), angiopoietin 2, vascular endothelial growth factor, and tumor necrosis factor-alpha. High levels of TGF-beta2 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;8908.86 pg/mL) and CD105 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4.25 ng/mL) were independently associated with improved overall survival (not reached vs 39 months, P = 0.009 and 75 vs 39 months, P = 0.029, respectively), whereas a high level of TGF-beta2 and a low level of vascular endothelial growth factor (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;219.04 pg/mL) were independently associated with improved progression-free survival (49 vs 17 months, P = 0.022 and 57 vs 16 months, P = 0.023, respectively). Among patients with favorable (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4.25 ng/mL) CD105 levels, only patients with low TGF-beta1 levels (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;177.1 ng/mL) had superior survival than patients with low CD105 levels. Our study confirms the prognostic significance of angiogenesis in EOC and supports a biological interaction between CD105 and TGF-beta1. High angiogenic activity may be associated by increased efficacy of postoperative chemotherapy.
Research Interests: Chemotherapy, Medicine, Angiogenesis, Humans, Internal Medicine, and 15 moreFemale, Young Adult, Aged, Middle Aged, Adult, Retrospective Studies, Prognosis, Transforming Growth Factor Beta, Gynecological cancer, Antineoplastic Agents, Gynecologic Cancer, Vascular Endothelial Growth Factor, Transforming Growth Factor, Endoglin, and Ovarian Neoplasms
Background: Primary fallopian tube carcinoma (PFTC) is a rare gynecologic malignancy with very few data existing on the activity of the combination of paclitaxel with a platinum analogue as adjuvant chemotherapy. Methods: We... more
Background: Primary fallopian tube carcinoma (PFTC) is a rare gynecologic malignancy with very few data existing on the activity of the combination of paclitaxel with a platinum analogue as adjuvant chemotherapy. Methods: We retrospectively analyzed 41 consecutive patients with PFTC who were treated postoperatively with paclitaxel- and platinum-containing chemotherapy regimens. Results: We observed 12 (63.2%) complete and 6 (31.6%) partial responses among 19 patients with measurable disease. The median time to disease progression (TTP) for all patients was 68 months. The median overall survival (OS) for all patients has not been reached yet. The median TTP was 84 months for patients with stage I/II disease and 34 months for patients with advanced disease (p = 0.017). Median OS has not been reached yet for patients with stage I/II PFTC, while it was 63.8 months for patients with stage III/IV disease (p = 0.002). Furthermore, OS has not been reached yet for patients with optimally debulked tumors, while it was 34.1 months for patients with residual disease &gt;2 cm (p &lt; 0.0001). Conclusion: Adjuvant platinum- and paclitaxel-based chemotherapy should be regarded as the standard treatment in patients with PFTC. Early stage disease and optimal debulking are associated with improved TTP and OS.
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Research Interests: Chemotherapy, Ovarian Cancer, Medicine, Humans, Female, and 15 moreClinical Sciences, Aged, Middle Aged, Combination chemotherapy, Bone Marrow Transplantation, Adult, Randomized Controlled Trial, Disease Progression, Cyclophosphamide, Overall Survival, Carboplatin, Hematopoietic Stem Cell Transplantation, Combined Modality Therapy, epithelial ovarian cancer, and Ovarian Neoplasms
Stage I testicular nonseminomatous germ-cell tumors (NSGCT) are highly curable. Following orchidectomy surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection can be applied. Certain factors are used to select... more
Stage I testicular nonseminomatous germ-cell tumors (NSGCT) are highly curable. Following orchidectomy surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection can be applied. Certain factors are used to select patients in high-risk for relapse. We report the outcome and safety of a risk-adapted strategy by the Hellenic Cooperative Oncology Group. Between 1994 and 2004, 142 patients with stage I NSGCT and 1 of the following risk factors: lymphovascular invasion (LVI), invasion of tunica vaginalis, spermatic cord, rete testis or scrotal wall, embryonal component &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% of the total tumor, were prospectively included in a protocol of adjuvant chemotherapy consisting of two 3-week courses of bleomycin 15 IU, etoposide 120 mg/m(2), and cisplatin 40 mg/m(2) for 3 consecutive days with G-CSF support. Median follow-up was 79 months and 138 patients have been followed for at least 2 years. Seventy-seven patients (54%) had LVI and 74 (52%) had &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% embryonal component. There was 1 relapse, which was cured with chemotherapy and surgery. Another patient died due to disease-unrelated causes and 1 patient developed a new primary of the remaining testicle, which was cured with surgery. Two cycles of bleomycin/etoposide/cisplatin is an effective and safe form of adjuvant therapy in high-risk stage I NSGCT.
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4586 Background: Limited data exists on outcomes for mRCC patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counseling and clinical trial design. Methods: Outcomes of mRCC patients from the... more
4586 Background: Limited data exists on outcomes for mRCC patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counseling and clinical trial design. Methods: Outcomes of mRCC patients from the IMDC treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared and adjusted by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) benchmarks were calculated using different population inclusion criteria. OS and PFS are calculated from the line of therapy under consideration unless otherwise specified. Results: 2,705 patients were treated with TT of which 1,533 (57%) received only 1st-line TT, 734 (27%) received 2 lines of TT, and 438 (16%) received 3+ lines of TT. The median OS of patients that received 1, 2 or 3+ lines of TT starting from initial TT was 14.9, 21.0, and 39.2 months, respectively (p<0.0001). On multivariable analysis adjusting for baseline Heng prognostic factors, the use of 2nd-...
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4578 Background: A small subset of localized RCC patients will experience disease recurrence ≥5 years after nephrectomy. Clinical outcome of patients with LR has not been well characterized. Methods: Patients with mRCC treated with... more
4578 Background: A small subset of localized RCC patients will experience disease recurrence ≥5 years after nephrectomy. Clinical outcome of patients with LR has not been well characterized. Methods: Patients with mRCC treated with targeted therapy were retrospectively characterized according to time to relapse. Replase was defined as diagnosis of recurrent metastatic disease >3 months after initial diagnosis. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as Early Relapsers (ER) if they recurred within 5 years while Late Relapsers (LR) recurred after 5 years. Demographics and outcomes were compared. Results: 1210 mRCC patients were identified; 903 (74.6%) with relapse within the first 5 years, 200 (16.5%) within >5-10 years, and 107 (8.8%) after 10 years (range 10-35 years). Baseline characteristics are presented in the Table. Overall response rates to targeted therapy were better in LR vs. ER (35% vs. 24%; p=0.009). LR pa...
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4510 Background: The combinations of methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), cisplatin (MVAC) and gemcitabine, cisplatin (GC) are standard regimens for advanced urothelial cancer. Dose-dense (DD) MVAC prolonged... more
4510 Background: The combinations of methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), cisplatin (MVAC) and gemcitabine, cisplatin (GC) are standard regimens for advanced urothelial cancer. Dose-dense (DD) MVAC prolonged progression-free survival (PFS) compared to classic MVAC (Sternberg 2001). Recent data also suggested a benefit by increased gemcitabine dose density (Sternberg 2001). METHODS We initiated a phase III, randomized study of DD MVAC (M 30mg/m2, V 3mg/m2, A 30mg/m2, C 70mg/m2 q 2 wks) vs. DD GC (G 2500mg/m2, C 70mg/m2 q 2 wks) (with G-CSF). Patients with advanced transitional cell urothelial carcinoma, PS < 2 and CrCl > 50 were eligible. Accrual closed at 130 patients. This analysis also includes 61 patients who subsequently received DD MVAC, in order to increase the statistical power. Selection criteria, doses and follow-up were identical to that of the randomized study. RESULTS 174 eligible patients were analysed: DD MVAC (n=118) and DD GC (n=57). Groups were well balanced for baseline characteristics, although a non-significant higher frequency of PS 0 (64% vs. 46%, p=0.064) was noted in the MVAC arm. Median fup was 39 months. Efficacy results were similar (Table). Nevertheless, subgroup analysis suggested a superiority of DD GC among patients with PS 1 (Table). This interaction was significant (p=0.018 for OS and 0.083 for PFS). Grade 3/4 toxicities included myelosuppression (48% vs. 42%), neutropenic infections (12% vs. 8%), GI (15% vs. 6%), and constitutional symptoms (14% vs. 6%). CONCLUSIONS DD GC was not superior to DD MVAC but a benefit in symptomatic patients by DD GC was suggested. DD GC is more convenient than the conventional weekly GC and could be an alternative to the existing standards for advanced urothelial cancer. [Table: see text].
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Research Interests: Medicine, Humans, Internal Medicine, Low Dose, Male, and 15 moreClinical Sciences, Aged, Middle Aged, ALOPECIA, Disease Progression, Imidazoles, Bone Metastases, Life tables, Adenocarcinoma, Docetaxel, Combined Modality Therapy, Disease Free Survival, Liver neoplasms, lung neoplasms, and Androgen antagonists
Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy. Data was extracted from 147 patients with FIGO... more
Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy. Data was extracted from 147 patients with FIGO stage IA/IB, grade 2/3 or stage IC/IIA (any grade) who underwent primary surgery followed by paclitaxel/carboplatin chemotherapy. Median follow-up was 88 months. Ten-year relapse-free (RFS) and disease-specific survival (DSS) were: 81% (95% confidence interval [CI]: 73-89) and 81% (95% CI: 73-89). On multivariate analysis, non serous histology was associated with reduced risk for RFS (0.294, 95% CI: 0.112-0.577, p=0.001) and DSS (0.194, 95% CI: 0.075-0.504, p=0.001), while high-risk category (stage IC/IIA and grade 2/3) with increased risk for RFS (3.989, 95% CI: 1.189-13.389, p=0.009) and DSS (3.989, 95% CI: 1.064-16.386, p=0.038). The combination of histology and grade identified 3 groups with distinctly different 10-year RFS and DSS rates (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001): grade 1 (100% and 100%), non-serous grade 2/3 (83% and 86%) and serous grade 2/3 (60% and 60%). Serous histology is an adverse prognostic factor in early-stage ovarian cancer treated with adjuvant paclitaxel/carboplatin. Risk stratification according to histology and grade is a useful discriminator of prognosis and can be used in the design of future studies.
Research Interests: Oncology, Chemotherapy, Ovarian Cancer, Medicine, Multivariate Analysis, and 14 moreHumans, Internal Medicine, Gynecologic Oncology, Female, Paclitaxel, Middle Aged, Prognosis, Gynecologic, Carboplatin, epithelial ovarian cancer, Disease Free Survival, Neoplasm staging, Paediatrics and reproductive medicine, and Ovarian Neoplasms
Research Interests: Oncology, Clinical Trial, Medicine, Humans, Internal Medicine, and 15 moreRad, Female, Renal cell Carcinoma, Male, Everolimus, Aged, Middle Aged, Adult, Antineoplastic Agents, Protein Kinase Inhibitors, Immunosuppressive Agents, Adverse effect, react, Neoplasm metastasis, and Metastatic Renal Cell Carcinoma
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Renal failure (RF) is a common and severe complication of patients with multiple myeloma (MM). The purpose of our study was to assess the incidence of RF in a contemporary series of newly diagnosed patients with MM, its association with... more
Renal failure (RF) is a common and severe complication of patients with multiple myeloma (MM). The purpose of our study was to assess the incidence of RF in a contemporary series of newly diagnosed patients with MM, its association with specific clinical and laboratory features, and its impact on patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; outcome. Over the last decade, 756 newly diagnosed symptomatic patients with MM were included in our database. Renal failure, defined as a serum creatinine &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or= 2 mg/dl at the time of diagnosis, was seen in 21% of patients. Multiple parameters were associated with RF, but logistic regression analysis showed that RF was independently associated only with International Staging System and Bence Jones proteinuria. The presence of RF was associated with a trend for higher early death rate but with a similar response to primary therapy. The median survival of patients with RF was 19.5 months versus 40.4 months for patients without RF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Several variables were associated with impaired survival by univariate analysis. When multivariate analysis was performed the independent variables were poor performance status, thrombocytopenia, advanced age, high LDH and elevated serum beta2 microglobulin but not high creatinine. When corrected for stage, renal failure had no impact on survival.