-
International Urology and Nephrology Apr 2023Prostate cancer (PCa) is the second largest male tumor in the world and one of the most common malignant tumors in the urinary system. In recent years, the incidence... (Review)
Review
CONTEXT
Prostate cancer (PCa) is the second largest male tumor in the world and one of the most common malignant tumors in the urinary system. In recent years, the incidence rate of PCa in China has been increasing year by year. Meanwhile, refractory hormone resistance and adverse drug reactions of advanced PCa cause serious harm to patients.
OBJECTIVE
The present study aims to systematically review the recent advances in molecularly targeted drugs for prostate cancer and to use the retrieval and analysis of the literature library to summarize the adverse effects of different drugs so as to maximize the treatment benefits of targeted therapies.
EVIDENCE ACQUISITION
We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to March 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Medical Subject Heading (MeSH) terms and keywords such as (prostate cancer) AND (molecular target drugs) AND (side effect) were used. No language restrictions were set on the search process, and all these results were processed independently by two authors. Consensus was reached through discussion once met with any disagreements. The primary endpoint was differential features between different molecular targeted drugs. Secondary endpoints were side effects of different drugs on the body and corresponding prognostic values.
EVIDENCE SYNTHESIS
The Cochrane Collaboration risk of bias tool was used to assess the study quality in terms of sequence generation, allocation concealment, blinding, the completeness of outcome data, selective reporting and other biases. We retrieved 332 articles, of which 49 met the criteria for inclusion. Included studies show that prostatic tumor cells, tumor neovascularization and immune checkpoints are the main means for targeted therapy. Common drugs include 177 Lu-PSMA, Olaparib, Rucaparib, Bevacizumab, Pazopanib, Sorafenib, Cabozantinib, Aflibercept, Ipilimumab, Atezolizumab, Avelumab, Durvalumab. A series of publicly available data suitable for further analysis of side effects. An over-representation analysis of these datasets revealed reasonable dosage and usage is the key to controlling the side effects of targeted drugs. Important information such as the publication year, the first author, location and outcome observation of adverse effects was extracted from the original article. If the study data has some insufficient data, contacting the corresponding authors is necessary. All the studies included prospective nonrandomized and randomized research. Retrospective reviews were also screened according to the relevant to the purpose of this study. Meeting abstracts as well as letters to the editor and editorials were excluded.
STATISTICAL ANALYSIS
Data analysis was based on Cochrane's risk of bias tools to obtain the quality assessment. The included randomized studies used RoB2 and non-randomized ones corresponded to ROBINS-I. Standardized mean differences (SMD) were used to determine relative risk (RR) and side effects between groups. The eggers' test was used to check the publication bias from variable information in the included studies. All p < 0.05 were considered to be significant, and 95% was set as the confidence interval.
CONCLUSIONS
With the approval of a variety of targeted drugs, targeted therapy will be widely used in the treatment of advanced or metastatic prostate cancer. Despite the existence of adverse reactions related to targeted drug treatment, it is still meaningful to adjust the drug dosage or treatment cycle to reduce the occurrence of adverse reactions, improving the treatment benefits of patients.
Topics: Humans; Male; Molecular Targeted Therapy; Prospective Studies; Retrospective Studies; Prostatic Neoplasms; Prostate
PubMed: 36719528
DOI: 10.1007/s11255-023-03487-3 -
Cancers Oct 2022Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about... (Review)
Review
Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations.
PubMed: 36358734
DOI: 10.3390/cancers14215315 -
Frontiers in Pharmacology 2022Multiple targeted therapeutics are available for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), but it remains unclear which treatment is optimal to...
Multiple targeted therapeutics are available for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), but it remains unclear which treatment is optimal to achieve long-term survival. A systematic search of the PubMed, Embase, and ClinicalTrials.gov databases was conducted to identify eligible randomized controlled trials (RCTs) comparing the efficacy and safety of targeted treatments for patients with RAIR-DTC from inception to April, 2022. Data were extracted by following the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. We calculated the odds ratio (OR) or hazard ratio (HR), its corresponding 95% credible intervals (CrI), and the surface under the cumulative ranking curve (SUCRA) to indicate ranking probability using Bayesian network meta-analyses. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade 3 or higher adverse events. A total of 12 eligible RCTs involved 1,959 patients and 13 treatments: apatinib, cabozantinib, anlotinib, nintedanib, lenvatinib, lenvatinib with low dose (LD), sorafenib, sorafenib plus everolimus, donafenib (200 mg), donafenib (300 mg), pazopanib (continuous), pazopanib (intermittent), and vandetanib. Pooled analyses indicated that targeted therapeutics significantly prolonged PFS and OS in patients with RAIR-DTC (0.31, 0.21-0.41; 0.69, 0.53-0.85, respectively) compared with placebo. Network meta-analyses indicated that lenvatinib showed the most favorable PFS, with significant differences versus sorafenib (0.33, 0.23-0.48), vandetanib (0.31, 0.20-0.49), nintedanib (0.30, 0.15-0.60), and placebo (0.19, 0.15-0.25), while apatinib was most likely to be ranked first for prolonging OS with a SUCRA of 0.90. Lenvatinib showed the highest ORR (66%, 61%-70%), followed by anlotinib (59%, 48%-70%) and apatinib (54%, 40%-69%). Lenvatinib caused the most adverse events of grade 3 or higher, followed by lenvatinib (LD) and apatinib. Different toxicity profiles of individual treatment were also revealed. This network meta-analysis suggests that lenvatinib and apatinib were associated with the best progression-free survival and overall survival benefits, respectively, for patients with RAIR-DTC, compared with other targeted therapeutics. Patients who received lenvatinib or apatinib also had more grade 3 or higher adverse events. : [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=302249], identifier [CRD42022302249].
PubMed: 36091770
DOI: 10.3389/fphar.2022.933648 -
Critical Reviews in Oncology/hematology Jul 2022To assess comparative effectiveness of adjuvant therapies for renal cell carcinoma and quantify the absolute benefit of adjuvant treatments by clinicopathological risk... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess comparative effectiveness of adjuvant therapies for renal cell carcinoma and quantify the absolute benefit of adjuvant treatments by clinicopathological risk groups.
METHODS
This 'living' review was conducted using Living Interactive Evidence (LIvE) synthesis framework.
RESULTS
The 'living' results are available on an interactive website. This network meta-analysis, including six RCTs with 7525 participants, showed that pembrolizumab (rank 1) significantly improved disease-free survival and overall survival compared with sunitinib but not when compared to pazopanib, and axitinib. The risk of treatment-related grade 3 or higher adverse events was increased with pembrolizumab as compared to placebo and axitinib but not when compared to sunitinib. The absolute benefit of adjuvant pembrolizumab increases substantially with larger tumor size, nodal positivity and higher Leibovich scores.
CONCLUSION
Current evidence suggests that pembrolizumab delays disease progression compared to sunitinib. A risk-adapted strategy should be used in patients undergoing consideration for treatment with adjuvant pembrolizumab.
Topics: Axitinib; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Network Meta-Analysis; Sunitinib
PubMed: 35537621
DOI: 10.1016/j.critrevonc.2022.103706 -
Computational and Mathematical Methods... 2022The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic renal cell carcinoma (RCC).
METHODS
Studies eligible for the efficacy of adjuvant targeted therapy regimens in advanced or metastatic RCC published before December 2021 in PubMed, Embase, Cochrane Clinical Trials Database (CENTRAL), and Web of Science were searched for (1) patients with locally advanced renal cell carcinoma (RCC) who received adjuvant postoperative targeted therapy versus those not receiving active treatment; (2) primary endpoint outcomes of disease-free survival (DFS), overall survival (OS), and adverse events (AEs); and (3) design: randomized controlled trial (RCT) as inclusion criteria. Data on DFS and OS were extracted or recalculated by meta-analysis as hazard ratios (HRs), and AEs were compared using a dominance ratio (OR).
RESULT
This systematic evaluation will provide evidence on the effectiveness and adverse effects of adjuvant targeted therapy in patients with advanced RCC. The results of meta-analysis showed that all of the three adjuvant targeted therapeutic drugs (sorafenib, sunitinib, and pazopanib) did not benefit from the adjuvant targeted therapy for DFS and OS and even increase the incidence of AEs compared to the placebo.
CONCLUSIONS
The aim of this study was to summarize data on DFS, OS, and AEs in patients with advanced RCC treated with targeted therapies. The evidence provided by this systematic evaluation and meta-analysis will help guide clinical decision-making and provide insight into the future management of patients with advanced RCC.
Topics: Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Humans; Kidney Neoplasms
PubMed: 35392587
DOI: 10.1155/2022/7341294 -
Scientific Reports Mar 2022The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis... (Meta-Analysis)
Meta-Analysis
The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis (NMA) to synthesize evidence of their comparative effectiveness for improving overall survival (OS) among EOC patients. We searched six databases for randomized controlled trials (RCTs) from their inception to February 2021. We performed an NMA with hazard ratios (HRs) and 95%-confidence intervals (CIs) to evaluate comparative effectiveness among different AAAs in chemotherapy-naïve and recurrent EOC. P-score was used to provide an effectiveness hierarchy ranking. Sensitivity NMA was carried out by focusing on studies that reported high-risk chemotherapy-naïve, platinum-resistant, and platinum-sensitive EOC. The primary outcome was OS. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). The NMA indicated that bevacizumab plus chemotherapy followed by maintenance bevacizumab (P-score: 0.99) and pazopanib combined with chemotherapy (P-score: 0.79) both had the highest probability of being the best intervention for improving OS in high-risk chemotherapy-naïve and platinum-resistant EOC, respectively. AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC.
Topics: Angiogenesis Inhibitors; Bevacizumab; Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Network Meta-Analysis; Ovarian Neoplasms
PubMed: 35264616
DOI: 10.1038/s41598-022-07731-1 -
Musculoskeletal Surgery Mar 2023Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered... (Review)
Review
Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.
Topics: Humans; Vinorelbine; Sorafenib; Imatinib Mesylate; Hydroxyurea; Fibromatosis, Aggressive; Watchful Waiting; Methotrexate; Doxorubicin
PubMed: 35150408
DOI: 10.1007/s12306-022-00738-x -
European Journal of Cancer (Oxford,... Sep 2021The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void.
MATERIAL AND METHODS
We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative.
RESULTS
Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO.
CONCLUSION
Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.
Topics: Female; Humans; Kidney Neoplasms; Male; Neoplasm Metastasis; Protein Kinase Inhibitors; Time Factors
PubMed: 34392067
DOI: 10.1016/j.ejca.2021.07.014 -
Anti-cancer Drugs Jan 2022Pyoderma gangrenosum is a rare ulcerative dermatosis. It may be caused by some drugs, including small molecule tyrosine kinase inhibitors (TKIs). The aim of this study...
Pyoderma gangrenosum is a rare ulcerative dermatosis. It may be caused by some drugs, including small molecule tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the reported evidence of pyoderma gangrenosum associated with the use of these drugs. A systematic electronic literature search of PubMed and Embase was conducted. In these databases, search terms describing pyoderma gangrenosum were combined with TKIs. Fifteen case reports (eight cases associated with sunitinib, two with imatinib, two with ibrutinib, one with gefitinib, one with pazopanib, and one with dabrafenib and trametinib) were identified over the 14 years. The average Naranjo score of these cases is 6.6, which indicates a probable adverse drug reaction. Pyoderma gangrenosum is a probable and reversible drug reaction associated with some TKIs. Detailed medical history can help to prompt diagnosis of drug-induced pyoderma gangrenosum. Clinicians should be aware of TKI-associated pyoderma gangrenosum when caring for the skin of oncologic patients undergoing therapy with kinase inhibitors.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Patient Acuity; Protein Kinase Inhibitors; Pyoderma Gangrenosum
PubMed: 34282745
DOI: 10.1097/CAD.0000000000001140 -
Journal of Cancer Research and Clinical... Aug 2021The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase... (Comparative Study)
Comparative Study Meta-Analysis
Comparative evaluation of cardiovascular risks among nine FDA-approved VEGFR-TKIs in patients with solid tumors: a Bayesian network analysis of randomized controlled trials.
PURPOSE
The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors.
METHODS
Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for the randomized controlled trials. We have included 45 randomized controlled trials (RCTs) associated with nine VEGFR-TKIs Food and Drug Administration (FDA)-approved drugs used to treat patients with solid tumors. To evaluate the trials' risk of bias, Cochrane Risk of Bias Tool was assessed. A direct comparison was assessed by RevMan5.3 software, calculating the odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was tested by the I statistic and Chi-square test for P value. Bayesian network meta-analysis was performed using Stata 15.0 and GeMTC 0.14.3 software, calculated OR along with corresponding 95% credible interval (CrI). The model's convergence was evaluated by the potential scale reduced factor (PSRF). Consistency between direct and indirect comparisons was assessed by the "node-splitting" method.
RESULTS
In this network meta-analysis, a total of 20,027 patients from 45 randomized controlled trials and associated with nine FDA-approved VEGFR-TKIs (axitinib, cabozantinib, lenvatinib, nintedanib, pazopanib, regorafenib, sorafenib, sunitinib, vandetanib), were enrolled. Findings indicated that lenvatinib had the most significant probability of provoking all grades cardiovascular incident and hypertension, followed by vandetanib, cabozantinib, axitinib, pazopanib, sorafenib, sunitinib, regorafenib and nintedanib. The nine agent's severe cardiovascular and severe hypertension risk was probably similar. The ranking probability of cardiac toxicity shows that vandetanib ranked most likely to have the highest risk for cardiotoxicity among all the VEGFR-TKIs reviewed, followed by pazopanib, axitinib, sorafenib, sunitinib. In contrast, regorafenib and nintedanib did not exhibit an increased risk of cardiac damage.
CONCLUSIONS
The association between the nine VEGFR-TKIs with potential cardiotoxicity occurrence was reviewed. Both the regorafenib and nintedanib did not display detectable signs of cardiotoxic damage. In contrast, lenvatinib and vandetanib are ranked to have the most severe cardiotoxicity side impacts. These results may provide information for clinical practice guidelines, implementing strategies in selecting the adequate VEGFR-TKIs, and understanding the cardiovascular toxicity inflicted by the VEGFR-TKIs.
PROSPERO IDENTIFIER
CRD 42,020,167,307.
Topics: Bayes Theorem; Cardiotoxicity; Cardiovascular Diseases; Drug Approval; Drug-Related Side Effects and Adverse Reactions; Heart Disease Risk Factors; Humans; Neoplasms; Network Meta-Analysis; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; United States; United States Food and Drug Administration; Vascular Endothelial Growth Factor A
PubMed: 33725154
DOI: 10.1007/s00432-021-03521-w