The risk of proteinuria with the angiogenesis inhibitor axitinib in patients with cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 439-439 ◽  
Author(s):  
Andrew Kuei ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Significant Risk ◽  
Angiogenesis Inhibitor ◽  
Growth Factor Receptor ◽  
High Grade ◽  
Treatment Interruptions ◽  
Significant Difference

439 Background: The use of axitinib, a potent inhibitor of the vascular endothelial growth factor receptor (VEGFR), is associated with proteinuria, which may cause morbidity and treatment interruptions in cancer patients. We performed a systematic review and meta-analysis of published clinical trials to assess the overall risk of severe proteinuria when treated with axitinib. Methods: Potentially relevant studies were identified by searching databases from PubMed and abstracts presented at the American Society of Clinical Oncology annual meetings until June 2012. Eligible studies included prospective clinical trials in cancer patients treated with axitinib containing data on all-grade and/or high-grade proteinuria. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated using the fixed- or random-effects models. Results: A total of 1,671 patients with advanced renal cell carcinoma (RCC) and other solid tumors from 9 studies were included for analysis. The overall incidence of all-grade proteinuria with axitinib was 22.7% (95% CI: 10.4-42.6%). There was no significant difference between RCC and non-RCC patients (p = 0.45), although the incidence in RCC patients was higher (30.0%, 95% CI: 8.4-66.7 vs. 17.5%, 95% CI: 7.4-36.3%). The overall incidence of high-grade (grade 3 or 4) proteinuria with axitinib was 3.8% (95% CI: 2.6-5.7%). In comparison with a control (gemcitabine), axitinib significantly increased the incidence of high-grade proteinuria (3.3%, 95% CI: 1.6-6.5% vs. 0.1%, 95% CI: 0-2.3%; p=0.031). When compared to sorafenib, another angiovsgenesis inhibitor, axitinib has elevated risk of proteinuria but without statistical significance (RR=1.48 for all-grade, 95% CI: 0.92-2.38, p = 0.10; RR=1.81 for high-grade, 95% CI: 0.68-4.85, p = 0.24). Conclusions: There was a significant risk of high-grade proteinuria associated with the use of axitinib in cancer patients. Adequate monitoring and appropriate use of axitinib is recommended to reduce renal complications.

Risk of proteinuria with the new angiogenesis inhibitor axitinib in patients with cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20602-e20602
Author(s):  
Andrew Kuei ◽  
Xiaolei Zhu ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Significant Risk ◽  
Angiogenesis Inhibitor ◽  
Growth Factor Receptor ◽  
High Grade ◽  
Random Effects Models ◽  
Treatment Interruptions ◽  
Significant Difference

e20602 Background: The use of axitinib, a potent inhibitor of vascular endothelial growth factor receptor (VEGFR), is associated with proteinuria, which may cause morbidity and treatment interruptions in cancer patients. We performed a systematic review and meta-analysis of published clinical trials to assess the overall risk of proteinuria with axitinib. Methods: Potentially relevant studies were identified by searching databases including Pubmed and abstracts presented at the American Society of Clinical Oncology annual meetings until June, 2012. Eligible studies included prospective clinical trials in cancer patients treated with axitinib containing data on proteinuria. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated using the fixed- or random-effects models. Results: A total of 1,671 patients with advanced renal cell carcinoma (RCC) and other solid tumors from 9 studies were included for analysis. The overall incidences of all-grade and high-grade (grade 3 or 4) proteinuria with axitinib were 22.7% (95% CI: 10.4-42.6%) and 3.8% (95% CI: 2.6-5.7%) respectively. The risk did not vary significantly with tumor types (P=0.13). There was no significant difference between RCC and non-RCC patients (P=0.45), although the incidence in RCC patients was higher (30.0%, 95% CI: 8.4-66.7 versus 17.5%, 95% CI: 7.4-36.3%). In comparison with a control (gemcitabine), axitinib significantly increased the incidence of high-grade proteinuria (3.3%, 95% CI: 1.6-6.5% versus 0.1%, 95% CI: 0-2.3%; P=0.031). When compared to another angiogenesis inhibitor sorafenib, axitinib did not have a significantly higher risk of all-grade (RR=1.48, 95% CI: 0.92-2.38, P=0.10) and high-grade proteinuria (RR=1.81, 95% CI: 0.68-4.85, P=0.24). Conclusions: There was a significant risk of proteinuria associated with the use of axitinib in cancer patients.

Risk of pneumonitis with mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13573-e13573
Author(s):  
Vishal Navnitray Ranpura ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Therapeutics ◽  
Mtor Inhibitors ◽  
High Grade ◽  
Significant Difference ◽  
American Society

e13573 Background: Pneumonitis is associated with the use of mTOR inhibitors, everolimus and temsirolimus, which have been used widely in cancer therapeutics and clinical trials. Currently, the overall risk of pneumonits in patients treated with mTOR inhibitors has not been defined. We performed a systematic review and meta-analysis of published clinical trials to assess the risk of pneumonitis in cancer patients treated with mTOR inhibitors. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences until May 2012 were searched to identify relevant studies. Eligible studies included prospective clinical trials in which patients received treatment with everolimus or temsirolimus as a single agent or in combination with other agents. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated employing a fixed- or random-effects model based upon the heterogeneity of the included studies. Results: A total of 2,303 patients with a variety of tumors from 18 studies (everolimus: 12, temsirolimus: 6) were included for the analysis. The overall incidences of all-grade and high-grade pneumonitis with mTOR inhibitors were 6.5% (95% CI: 3.7-11.1%) and 2.5% (95% CI 1.2-5.4%) respectively. The risk of all-grade pneumonitis did not vary significantly with tumor types (P=0.079), but vary significantly with their combination with other agents (P<0.001). There was no significant difference between everolimus and temsirolimus in the incidence of all-grade (P=0.22) and high-grade (P=0.28) pneumonitis. In comparison with controls, mTOR inhibitors significantly increased the risk of all-grade (RR=5.2, 95% CI: 2.09-12.93, P<0.001) but not high-grade pneumonits (RR=2.63, 95% CI: 0.66-10.40, P=0.41). Conclusions: The risk of pneumonitis is increased in cancer patients receiving mTOR inhibitors without significant difference between everolimus and temsirolimus.

Risk of rash associated with lenalidomide in multiple myeloma and myelodisplastic syndrome: A systematic review of the literature and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18571-e18571
Author(s):  
Benjamin C Garden ◽  
Beatrice Nardone ◽  
Shenhong Wu ◽  
Dennis P. West ◽  
Romala Emmanuel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Significant Risk ◽  
High Grade ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

e18571 Background: Indications of lenalidomide (Len) include treatment of multiple myeloma (MM) in combination with dexamethasone (Dex) and myelodyplastic syndrome (MDS). The reported incidence and risk of rash varies widely and has been inconsistently reported in trials. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from PubMed (1998-2011), abstracts presented at ASCO conferences (2004-2011) and the Web of Science database (1998-2011). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received daily Len doses of either 10mg or 25 mg with or without 40mg of Dex. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 1,127 patients in 15 trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash was 29.9% (95% CI: 24.8- 35.5) and 3.8% (95% CI: 2.7-5.5), respectively. Len was associated with increased risk of all-grade rash (RR=1.7, 95% CI: 1.3-2.3; P<0.001) when compared to patients treated with a placebo and Dex. Risk of high-grade rash was increased (RR=3.7, 95% CI: 0.8-16.0) with a trend toward statistical significance (P=0.08). No significant difference in incidence of all-grade rash between patients receiving LEN doses of 10mg or 25mg (25.6%, 95% CI: 19.6-32.8% vs. 30.8%, 95% CI: 24.7-37.7%, respectively, p=0.28) was observed. Similarly, no difference was observed between patients receiving LEN monotherapy or in combination with Dex (31.0%, 95% CI: 26.6-43.3% and 23.8%, 95% CI: 14.9-35.8%, respectively, p=0.17). Conclusions: Patients with MM or MDS who are treated with Len are at significant risk for developing rash. The risk appears to be independent of LEN dosage or in combination with Dex. Further studies for prevention and treatment of this untoward toxicity are needed in order to maintain patient’s quality of life and minimize the need for dose modification, all of which may impact clinical outcome.

Hand–foot skin reaction, an anticipated dermatologic toxicity to pazopanib, with an unexpected low incidence: A systematic review of literature and meta-analysis.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 365-365 ◽  
Author(s):  
Y. Balagula ◽  
S. Wu ◽  
X. Su ◽  
M. E. Lacouture
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinases ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Statistical Significance ◽  
P Value ◽  
High Grade ◽  
Multikinase Inhibitor ◽  
Systematic Analysis ◽  
Dermatologic Toxicity

365 Background: Pazopanib is a novel multikinase inhibitor that has been approved for the treatment of advanced renal cell carcinoma (RCC). It shares a similar spectrum of target receptors with sorafenib and sunitinib, including VEGFR, PDGFR, and c-kit tyrosine kinases. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib. Exploring the differences in the incidence of HFSR between sorafenib, sunitinib, and pazopanib may offer additional insights into underlying mechanisms of this toxicity. Methods: Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 942 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.5% (95% CI: 0.7-3.1 %), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased, reaching statistical significance for all-grade (RR=6.05, 95% CI: 1.11-33.12, p=0.038), but not for high-grade (RR=2.51, 95% CI: 0.12-51.9, p=0.55). The incidence of all-grade HFSR was significantly higher in patients with RCC as compared to patients with non-RCC malignancies (7.8% vs. 2.4%, p value=0.015). Conclusions: Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis. [Table: see text]

Rash to mTOR inhibitor everolimus: Systematic review and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19624-e19624 ◽  
Author(s):  
Marigdalia K. Ramirez-Fort ◽  
Emily Christine Case ◽  
Alyx C. Rosen ◽  
Shenhong Wu ◽  
Mario E. Lacouture
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Fixed Effects ◽  
Mtor Inhibitor ◽  
Meta Analysis ◽  
Significant Risk ◽  
Phase Iii ◽  
Subependymal Giant Cell Astrocytoma ◽  
High Grade ◽  
Increased Risk

e19624 Background: Everolimus is an mTOR inhibitor approved for treatment of renal cell carcinoma, subependymal giant cell astrocytoma, and progressive neuroendocrine tumors of pancreatic origin. Its use may be hindered due to adverse events, including rash. The reported incidence and risk of rash to everolimus varies widely and has not been closely investigated. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology from 1998 to July 2011 using the keyword “everolimus” to identify relevant clinical trials. Eligible studies included prospective phase II and phase III clinical trials of cancer patients on 10 mg of everolimus daily with available data on incidence of rash. The summary incidence and relative risk (RR) of rash were calculated using either the random-effects or fixed-effects model, depending on the heterogeneity of the constituent studies. Results: A total of 2,242 patients with various malignancies from 13 clinical trials were included in the analysis. The summary incidences of all-grade and high-grade rash in patients on everolimus were28.6% (95% CI: 20.8 – 38.0) and 1.0% (95% CI: 0.6 – 1.7), respectively. Everolimus was associated with a statistically significant increased risk of all-grade rash (RR=3.853, 95% CI: 2.470 – 6.013, p=0.000), but the RR for high-grade rash (RR= 2.997, 95% CI: 0.633 – 14.185) was not statistically significant, with a p value of 0.166. Conclusions: Everolimus is associated with a significant risk of developing rash. Management of rash to everolimus is critical to prevent dose modifications and decreased quality of life, both of which can negatively affect clinical outcomes.

Risk of rash with nilotinib: A systematic review of the literature and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9088-9088
Author(s):  
Aaron Mark Drucker ◽  
Shenhong Wu ◽  
Ellin Berman ◽  
Mario E. Lacouture
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Fixed Effects ◽  
Systemic Mastocytosis ◽  
Meta Analysis ◽  
Significant Risk ◽  
Myelogenous Leukemia ◽  
High Grade ◽  
Pubmed Database ◽  
Increased Risk

9088 Background: Nilotinib is indicated for the treatment of chronic myelogenous leukemia (CML). The reported incidence and risk of rash from this medication vary widely and have been inconsistently reported in published trials. Therefore we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing rash. Methods: Relevant studies were identified from the PubMed database (1998-2012), abstracts presented at ASCO and ASH Conferences (2004-2011) and Web of Science database (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which patients received nilotinib at doses of either 300 mg or 400 mg twice daily. Incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: Data from a total of 3,186 patients receiving nilotinib in 16 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash were 33.1% (95% CI: 27.7-39.1) and 2.6% (95% CI: 2.1-3.4), respectively. Incidence of all-grade rash for patients with CML, gastrointestinal stromal tumor (GIST) and systemic mastocytosis were 33.2% (95% CI: 27.2-39.9), 25.7% (95% CI: 14.0-42.5) and 25.0% (95% CI: 15.7-37.4), respectively. Nilotinib was associated with increased risk of all-grade rash (RR=2.891, 95% CI: 2.079-4.020; P<0.001) when compared to patients treated with imatinib. Risk of high-grade rash was increased compared to imatinib (RR=1.823, 95% CI: 0.670-4.957), but this was not statistically significant (P=0.24). Conclusions: Patients with hematologic malignancies and GIST who are treated with nilotinib are at significant risk for developing a rash. Further studies for characterization, prevention and treatment of this untoward toxicity are needed in order to maintain patients’ quality of life and minimize the need for dose modification, which may impact clinical outcome.

Fatal adverse events associated with pembrolizumab in cancer patients: A meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2561-2561
Author(s):  
Gol Minoo Golshani ◽  
Amna Falak Sher ◽  
Shenhong Wu
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Random Effects Models ◽  
Programmed Cell Death 1 ◽  
Significant Difference ◽  
American Society ◽  
Fatal Adverse Events ◽  
Tumor Types

2561 Background: Pembrolizumab, an immune checkpoint inhibitor (ICI) against programmed cell death-1(PD-1) protein has emerged as an effective treatment for many cancers. Although better tolerated than chemotherapy, it has unique immune related adverse event and little is known about its risk of fatal adverse events (FAE). Therefore, we conducted a meta-analysis of clinical trials to determine the incidence and risk of fatal adverse events with pembrolizumab. Methods: A systematic search for phase I-III clinical trials of pembrolizumab was conducted using databases from PUBMED, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October 2018. Eligible studies included prospective clinical trials of pembrolizumab with available data on FAE. Data on FAE was extracted from each study and pooled for calculations. Incidence, relative risk (RR) and 95% confidence intervals (CI) were calculated by employing fixed or random-effects models. Results: A total of 11 clinical trials of pembrolizumab, with 3713 patients were included for analysis. The overall incidence of FAE with pembrolizumab was 1.2% (95% CI: 0.5-2.8%).The incidence of FAE significantly varied among different tumor types (P=0.02), ranging from 0.2% in melanoma to 3.1% in breast cancer.The incidence of FAE was significantly higher (P<0.001) with chemotherapy plus pembrolizumab (7.0%, 95%CI: 4.9-10%) as compared to pembrolizumab alone (0.7%, 95% CI: 0.4-1.2, p=<0.001). There was no significant difference in the risk of FAEs when pembrolizumab was compared with chemotherapy with RR=1.24 (95% CI: 0.8-1.89, P=0.31). Conclusions: Pembrolizumab is similar to chemotherapy in the risk of fatal adverse events in cancer patients. Combination of pembrolizumab with chemotherapy increased the risk of FAE in comparison with pembrolizumab alone. Further studies are needed to identify risk factors. [Table: see text]

scholarly journals High/Positive Expression of 5-Fluorouracil Metabolic Enzymes Predicts Better Response to S-1 in Patients with Gastric Cancer: A Meta-Analysis

2016 ◽  
Vol 31 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Dan Wang ◽  
Xuejun Yu ◽  
Xiuwen Wang
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Dihydropyrimidine Dehydrogenase ◽  
Objective Response ◽  
Metabolic Enzymes ◽  
Survival Ratio ◽  
Significant Difference ◽  
Gastric Cancer Patients

Purpose To provide an assessment by meta-analysis of the relationship between the expression variations of 5-fluorouracil metabolic enzymes and clinical outcomes in patients with gastric cancer treated with S-1. Method Databases were searched electronically from inception to April 19th, 2015. Studies in gastric cancer patients treated with S-1 investigating the expression variations of 5-fluorouracil metabolic enzymes were included after having been identified systematically. Pooled odds ratios (OR) for the objective response rate (ORR) and median survival ratio were calculated using the Review Manager 5.3 and Stata 12.0 software separately. Results A total of 555 patients in 10 studies met our inclusion criteria. There was a significant difference in ORR between patients with high/+ and low/- expression of orotate phosphoribosyl transferase (OPRT) (OR = 8.06; 95% CI, 4.06-16.02; p<0.001) and dihydropyrimidine dehydrogenase (DPD) (OR = 1.95; 95% CI, 1.21-3.13; p = 0.006). There was no significant difference in ORR between different expression levels of thymidylate synthase (TS) and thymidine phosphorylase (TP). Although patients with low/- TS expression, low/- TP expression and high/+ DPD expression showed a trend towards longer survival, no statistical significance was found. The median OS was significantly longer in patients with high/+ expression of OPRT (p = 0.076). Conclusions OPRT and DPD expression can be treated as a potential predictive biomarker for S-1 response in gastric cancer patients. Further investigation is warranted.

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