-
Cancer Cell International Sep 2023Paclitaxel is a natural anticancer compound with minimal toxicity, the capacity to stabilize microtubules, and high efficiency that has remained the standard of... (Review)
Review
Paclitaxel is a natural anticancer compound with minimal toxicity, the capacity to stabilize microtubules, and high efficiency that has remained the standard of treatment alongside platinum-based therapy as a remedy for a variety of different malignancies. In contrast, polyphenols such as flavonoids are also efficient antioxidant and anti-inflammatory and have now been shown to possess potent anticancer properties. Therefore, the synergistic effects of paclitaxel and flavonoids against cancer will be of interest. In this review, we use a Boolean query to comprehensively search the well-known Scopus database for literature research taking the advantage of paclitaxel and flavonoids simultaneously while treating various types of cancer. After retrieving and reviewing the intended investigations based on the input keywords, the anticancer mechanisms of flavonoids and paclitaxel and their synergistic effects on different targets raging from cell lines to animal models are discussed in terms of the corresponding involved signaling transduction. Most studies demonstrated that these signaling pathways will induce apoptotic / pro-apoptotic proteins, which in turn may activate several caspases leading to apoptosis. Finally, it can be concluded that the results of this review may be beneficial in serving as a theoretical foundation and reference for future studies of paclitaxel synthesis, anticancer processes, and clinical applications involving different clinical trials.
PubMed: 37743502
DOI: 10.1186/s12935-023-03052-z -
Frontiers in Pharmacology 2023Doxorubicin-induced cardiotoxicity represents a prevalent adverse effect encountered in patients undergoing treatment with doxorubicin. To date, there has been no...
Doxorubicin-induced cardiotoxicity represents a prevalent adverse effect encountered in patients undergoing treatment with doxorubicin. To date, there has been no bibliometric study to summarize the field of doxorubicin-induced cardiotoxicity. In our study, we aim to determine the current status and frontiers of doxorubicin-induced cardiotoxicity by bibliometric analysis. The documents concerning doxorubicin-induced cardiotoxicity are obtained from the Web of Science Core Collection database (WOSCC), and VOSviewer 1.6.16, CiteSpace 5.1.3 and the WOSCC's literature analysis wire were used to conduct the bibliometric analysis. In total, 7,021 publications were encompassed, which are produced by 37,152 authors and 6,659 organizations, 1,323 journals, and 101 countries/regions. The most productive author, institution, country and journal were Bonnie Ky with 35 publications, University of Texas with 190 documents, the United States with 1,912 publications, and with 120 documents. The first high-cited article was published in the NEJM with 8,134 citations authored by DJ Slamon et al., in 2001. For keyword analysis, there are four clusters depicted in distinct directions. The keywords in the red cluster are oxidative stress, apoptosis, and cardiomyopathy. The keywords in the green cluster are cardiotoxicity, heart failure, and anthracycline. The keywords in the blue cluster are chemotherapy, trastuzumab, and paclitaxel. The keywords in the purple cluster are doxorubicin, adriamycin, and cancer. Most of the documents were derived from the United States, China and Italy (4,080/7,021, 58.1%). The number of studies from other countries should be increased. In conclusion, the main research hotspots and frontiers in the field of doxorubicin-induced cardiotoxicity include the role of doxorubicin in cardiotoxicity, the mechanisms underlying doxorubicin-induced cardiotoxicity, and the development of treatment strategies for doxorubicin-induced cardiotoxicity. More studies are needed to explore the mechanisms and treatment of doxorubicin-induced cardiotoxicity.
PubMed: 38026961
DOI: 10.3389/fphar.2023.1255158 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
European Urology Oct 2021Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are... (Meta-Analysis)
Meta-Analysis
CONTEXT
Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates.
OBJECTIVE
To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD.
EVIDENCE ACQUISITION
A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist.
EVIDENCE SYNTHESIS
A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p < 0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p < 0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p = 0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen.
CONCLUSIONS
Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence.
PATIENT SUMMARY
We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.
Topics: Captopril; Humans; Injections, Intralesional; Male; Mitomycin; Recurrence; Tamoxifen; Triamcinolone; Urethra; Urethral Stricture
PubMed: 34275660
DOI: 10.1016/j.eururo.2021.06.022 -
BMC Cancer Jul 2021Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety and efficacy of nab-paclitaxel remain unclear which need to be systematically evaluated.
METHODS
Electronic searches for prospective clinical trials evaluating nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analysed from the included studies according to the different study designs using systematic review and meta-analysis. Meta-regression and subgroup analysis were further performed to explore the potential risk factors affecting each individual outcome of interest following nab-paclitaxel monotherapy.
RESULTS
Twenty-two studies with 3287 MBC patients were included. A total of 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. A total of 1966 MBC patients (60.40%) received nab-paclitaxel weekly, 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) received nab-paclitaxel biweekly. The overall incidence rates of all-grade neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue were 52% (95% CI, 38-66%, I = 98.97%), 58% (95% CI, 43-73%, I = 97.72%), 58% (95% CI, 48-68%, I = 97.17%), and 49% (95% CI, 41-56%, I = 94.39%), respectively. The overall response rate (ORR) was 40% (95% CI, 35-45%, I = 98.97%), and the clinical benefit rate (CBR) was 66% (95% CI, 59-73%, I = 98.97%) following nab-paclitaxel monotherapy. The median progression-free survival (PFS) was 7.64 months (95% CI, 6.89-8.40 months, I = 92.3%), and the median overall survival (OS) was 24.51 months (95% CI, 21.25-27.78 months, I = 92.7%). Treatment line, human epidermal growth factor receptor-2(Her-2)-negative status and dosage were found to be sources of heterogeneity among the included studies. According to the meta-regression and subgroup analysis, grade 3/4 neutropenia occurred less frequently in Her-2-negative patients than in the entire population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were not affected by the administration schedule. However, within the same schedule, patients appeared to have a superior ORR (P = 0.044) and longer PFS (P = 0.03) with an increasing dosage of nab-paclitaxel administered.
CONCLUSIONS
The benefits brought by nab-paclitaxel mono-chemotherapy in the treatment of MBC are considerable while the harm is generally manageable. Further study and validation are needed to figure out the roles which the dosage, schedule and other factors play actually in nab-paclitaxel chemotherapy.
Topics: Albumins; Breast Neoplasms; Female; Humans; Neoplasm Metastasis; Paclitaxel; Risk Factors; Treatment Outcome
PubMed: 34275458
DOI: 10.1186/s12885-021-08441-z -
Molecules (Basel, Switzerland) Apr 2023This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects... (Review)
Review
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required.
Topics: Polyphenols; Curcumin; Resveratrol; Antioxidants; Drug Therapy, Combination
PubMed: 37175156
DOI: 10.3390/molecules28093746 -
Cancers May 2023Pancreatic cystic lesions (PCL) represent an increasingly diagnosed condition with significant burden to patients' lives and medical resources. Endoscopic ultrasound... (Review)
Review
BACKGROUND
Pancreatic cystic lesions (PCL) represent an increasingly diagnosed condition with significant burden to patients' lives and medical resources. Endoscopic ultrasound (EUS) ablation techniques have been utilized to treat focal pancreatic lesions. This systematic review with meta-analysis aims to assess the efficacy of EUS ablation on PCL in terms of complete or partial response and safety.
METHODS
A systematic search in Medline, Cochrane and Scopus databases was performed in April 2023 for studies assessing the performance of the various EUS ablation techniques. The primary outcome was complete cyst resolution, defined as cyst disappearance in follow-up imaging. Secondary outcomes included partial resolution (reduction in PCL size), and adverse events rate. A subgroup analysis was planned to evaluate the impact of the available ablation techniques (ethanol, ethanol/paclitaxel, radiofrequency ablation (RFA), and lauromacrogol) on the results. Meta-analyses using a random effects model were conducted and the results were reported as percentages with 95% confidence intervals (95%CI).
RESULTS
Fifteen studies (840 patients) were eligible for analysis. Complete cyst resolution after EUS ablation was achieved in 44% of cases (95%CI: 31-57; 352/767; I = 93.7%), and the respective partial response rate was 30% (95%CI: 20-39; 206/767; I = 86.1%). Adverse events were recorded in 14% (95%CI: 8-20; 164/840; I = 87.2%) of cases, rated as mild in 10% (95%CI: 5-15; 128/840; I = 86.7%), and severe in 4% (95%CI: 3-5; 36/840; I = 0%). The subgroup analysis for the primary outcome revealed rates of 70% (95%CI: 64-76; I = 42.3%) for ethanol/paclitaxel, 44% (95%CI: 33-54; I= 0%) for lauromacrogol, 32% (95%CI: 27-36; I = 88.4%) for ethanol, and 13% (95%CI: 4-22; I = 95.8%) for RFA. Considering adverse events, the ethanol-based subgroup rated the highest percentage (16%; 95%CI: 13-20; I = 91.0%).
CONCLUSION
EUS ablation of pancreatic cysts provides acceptable rates of complete resolution and a low incidence of severe adverse events, with chemoablative agents yielding higher performance rates.
PubMed: 37174092
DOI: 10.3390/cancers15092627 -
PloS One 2022Clinical benefit of paclitaxel-coated devices for patients with peripheral arterial disease has been confirmed in randomized controlled trials (RCTs). A meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical benefit of paclitaxel-coated devices for patients with peripheral arterial disease has been confirmed in randomized controlled trials (RCTs). A meta-analysis published in 2018 identified late mortality risk over a long follow-up period due to use of paclitaxel-coated devices in the femoropopliteal arteries, which caused enormous controversy and debates globally. This study aims to further evaluate the safety of paclitaxel-coated devices by incorporating the most recently published data.
METHODS
We searched for candidate studies in PubMed (MEDLINE), Scopus, EMBASE (Ovid) online databases, government web archives and international cardiovascular conferences. Safety endpoints of interest included all-cause mortality rates at one, two and five years and the risk ratio (RR) was used as the summary measure. The primary analysis was performed using random-effects models to account for potential clinical heterogeneity.
FINDINGS
Thirty-nine RCTs including 9164 patients were identified. At one year, the random-effects model yielded a pooled RR of 1.06 (95% CI [0.87, 1.29]) indicating no difference in short-term all-cause deaths between the paclitaxel and control groups (crude mortality, 4.3%, 214/5025 versus 4.5%, 177/3965). Two-year mortality was reported in 26 RCTs with 382 deaths out of 3788 patients (10.1%) in the paclitaxel arm and 299 out of 2955 patients (10.1%) in the control arm and no association was found between increased risk of death and usage of paclitaxel-coated devices (RR 1.08, 95% CI [0.93, 1.25]). Eight RCTs recorded all-cause deaths up to five years and a pooled RR of 1.18 (95% CI [0.92, 1.51]) demonstrated no late mortality risk due to use of paclitaxel-coated devices (crude mortality, paclitaxel 18.2%, 247/1360 versus control 15.2%, 122/805).
CONCLUSIONS
We found no significant difference in either short- or long-term all-cause mortalities between patients receiving paclitaxel-coated and uncoated devices. Further research on the longer-term safety of paclitaxel usage (e.g., 8- or 10-year) is warranted.
REGISTRATION
PROSPERO, CRD42021246291.
Topics: Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Drug-Eluting Stents; Femoral Artery; Humans; Paclitaxel; Peripheral Arterial Disease; Risk Factors; Treatment Outcome
PubMed: 36227807
DOI: 10.1371/journal.pone.0275888 -
Journal of Ovarian Research Jul 2023Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis Review
Dose-dense regimen versus conventional three-weekly paclitaxel combination with carboplatin chemotherapy in first-line ovarian cancer treatment: a systematic review and meta-analysis.
BACKGROUND
Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer.
METHODS
An electronic search following PRISMA guidelines was conducted (Prospero registration number: CRD42020187622), and then a systematic review and meta-analysis of included literature were initiated to determine which regimen was better.
RESULTS
Four randomized controlled trials were included in the qualitative evaluation, and 3699 ovarian cancer patients were included in the meta-analysis. The meta-analysis revealed that the dose-dense regimen could prolong PFS (HR0.88, 95%CI 0.81-0.96; p = 0.002) and OS (HR0.90, 95%CI 0.81-1.02; p = 0.09), but it also increased the overall toxicity (OR = 1.102, 95%CI 0.864-1.405; p = 0.433), especially toxicity of anemia (OR = 1.924, 95%CI 1.548-2.391; p < 0.001), neutropenia (OR = 2.372, 95%CI 1.674-3.361; p < 0.001). Subgroup analysis indicated that the dose-dense regimen could significantly prolong not only PFS (HR0.76, 95%CI 0.63-0.92; p = 0.005 VS HR0.91, 95%CI 0.83-1.00; p = 0.046) but also OS (HR0.75, 95%CI 0.557-0.98; p = 0.037 VS HR0.94, 95%CI 0.83-1.07; p = 0.371) in Asian, and overall toxicity was significantly increased in Asians (OR = 1.28, 95%CI: 0.877-1.858, p = 0.202) compared to non-Asians (OR = 1.02, 95%CI 0.737-1.396, p = 0.929).
CONCLUSION
Paclitaxel dose-dense regimen could prolong PFS and OS, but it also increased the overall toxicity. Therapeutic benefits and toxicity of dose-dense are more obvious in Asians compared to non-Asians, which need to be further confirmed in clinical trials.
Topics: Humans; Female; Carboplatin; Paclitaxel; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Randomized Controlled Trials as Topic
PubMed: 37430376
DOI: 10.1186/s13048-023-01216-z -
World Journal of Oncology Oct 2023The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established.... (Review)
Review
BACKGROUND
The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established. We conducted an analysis of retrospective studies to assess the efficacy and safety of these two regimens by comparing their survival and safety outcomes in patients with PC.
METHODS
We conducted an extensive review of two electronic databases from inception till February 2023 to include all the relevant studies that compared FFX with GnP published and unpublished work. Retrospective studies were only included. Overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs), while objective response rate (ORR) and safety outcomes were pooled using odds ratios (ORs) with 95% confidence interval (CI) using the random effects model.
RESULTS
A total of 7,030 patients were identified in a total of 21 articles that were shortlisted. Pooled results concluded that neither FFX nor GnP was associated to increase the OS time (HR: 0.93, 95% CI: 0.83 - 1.04; P = 0.0001); however, FFX was more likely associated with increased PFS when compared to GnP (HR: 0.88, 95% CI: 0.81 - 0.97; P < 0.0001). ORR proved to be non-significant between the two regimens (OR: 0.90, 95% CI: 0.64 - 1.27; P = 0.15). Safety outcomes included neutropenia, anemia, thrombocytopenia and diarrhea. GnP was more associated with diarrhea (OR: 1.96, 95% CI: 1.22 - 3.15; P = 0.001), while FFX was seen to cause anemia (OR: 0.70, 95% CI: 0.51 - 0.98; P = 0.10) in PC patients. Neutropenia and thrombocytopenia were in-significant in the two drug regimens (OR: 1.10, 95% CI: 0.92 - 1.31; P = 0.33 and OR: 0.83, 95% CI: 0.60 - 1.13; P = 0.23, respectively).
CONCLUSION
FFX and GnP showed a significant difference in increasing the PFS, while no difference was observed while measuring OS. Safety outcomes showed that FFX and GnP shared similar safety profiles as FFX was associated with hematological outcomes, while GnP was more associated with non-hematological outcomes.
PubMed: 37869244
DOI: 10.14740/wjon1604