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Cancer Treatment Reviews Dec 2015Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation... (Review)
Review
BACKGROUND
Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite clinical response.
OBJECTIVE
Pharmacogenetic studies were reviewed for identification of genetic variants possibly underlying individual susceptibility to adverse events.
METHOD
We conducted a systematic search in Pubmed and Embase for pharmacogenetic reports with focus on commonly reported taxane-related gastrointestinal, hematological and neurological toxicities in adult patients with solid tumors. The findings from a total of 51 eligible studies are presented in a comprehensive way.
RESULTS
Most frequently investigated single nucleotide polymorphisms (SNPs) were located in genes encoding proteins affecting pharmacokinetics, such as drug transporters and genes of the cytochrome P450 family. Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8. Interest is also dedicated towards genes involved in pharmacodynamics, such as detoxification of reactive oxygen species, DNA repair, neuronal processes and microtubule function. Recent studies include variants in TUBB2A, EPHA5 and EPHA6 for a possible association with neurotoxicity. Variations in methodological approach, sample size, study design, treatment schedule and end-point of toxicity affect consistency of results.
CONCLUSION
This review illustrates the complexity to well design pharmacogenetic studies for validation of SNPs that may clarify differences in taxane-induced toxicities among individuals. Novel genes encoding cellular targets of taxanes deserve further analysis by means of robust patient cohorts and definition of objective end-points.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antineoplastic Agents; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Docetaxel; Gastrointestinal Diseases; Hematologic Diseases; Humans; Neurotoxicity Syndromes; Paclitaxel; Pharmacogenetics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, EphA5; Receptor, EphA6; Taxoids; Tubulin
PubMed: 26585358
DOI: 10.1016/j.ctrv.2015.10.010 -
BMC Cancer May 2018Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for...
BACKGROUND
Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials.
METHODS
We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.
RESULTS
Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.
CONCLUSION
NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Cervix Uteri; Chemoradiotherapy, Adjuvant; Clinical Trials as Topic; Female; Humans; Hysterectomy; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 29728073
DOI: 10.1186/s12885-018-4447-x -
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 -
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 -
Clinical Reviews in Allergy & Immunology Oct 2023Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first... (Review)
Review
Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.
PubMed: 37589840
DOI: 10.1007/s12016-023-08968-y -
Carbohydrate Polymers Sep 2022Paclitaxel, a clinical chemotherapy drug commonly used in the past few years, is greatly limited by its low therapeutic index. Starch and its derivatives have gained... (Review)
Review
Paclitaxel, a clinical chemotherapy drug commonly used in the past few years, is greatly limited by its low therapeutic index. Starch and its derivatives have gained wide interest from researchers owing to their unique hydrophilic and hydrophobic properties resulting from their various modifications, which exert the effect-enhancing and toxicity-reducing activity to paclitaxel in vivo and in vitro. This review summarizes the research progress toward different kinds of starch-based carriers, whether oral or injectable. In addition, we discuss the complex properties of starch derivatives toward physically complexed or chemically conjugated paclitaxel. The corresponding complex configurations are suggested. Starch-based carriers can act as permeability enhancers because they may interact with the unstirred water layer that separates hydrophobic drugs from biological membranes, even altering the barrier properties of the membrane. The information presented in this review may be used as a reference for future hydrophobic drug carrier studies.
Topics: Drug Carriers; Excipients; Hydrophobic and Hydrophilic Interactions; Paclitaxel; Starch
PubMed: 35698420
DOI: 10.1016/j.carbpol.2022.119628 -
Nanomedicine (London, England) Oct 2023Nab-paclitaxel is formulated to address several limitations of paclitaxel. A systematic review was done of several databases and a meta-analysis with a random-effects... (Meta-Analysis)
Meta-Analysis Review
Nab-paclitaxel is formulated to address several limitations of paclitaxel. A systematic review was done of several databases and a meta-analysis with a random-effects model was conducted to assess the efficacy and safety of nab-paclitaxel in metastatic gastric cancer (MGC). Included studies revealed that nab-paclitaxel provides a 30.4% overall response rate and 65.7% disease control rate in MGC patients. The overall survival was 9.65 months and progression-free survival was 4.48 months, associated with the treatment line and regimen. The highest incidence of grade 3 and higher treatment-related adverse events was for neutropenia (29.9%). Nab-paclitaxel provides better disease response and longer survival with manageable side effects in MGC compared with paclitaxel.
Topics: Humans; Stomach Neoplasms; Paclitaxel; Albumins; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 37982749
DOI: 10.2217/nnm-2022-0300 -
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 -
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 -
Cureus Aug 2023The chemotherapeutic agent paclitaxel has significantly enhanced the treatment of various types of cancer. However, the quality of life of cancer patients is often... (Review)
Review
The chemotherapeutic agent paclitaxel has significantly enhanced the treatment of various types of cancer. However, the quality of life of cancer patients is often impacted by the painful and dose-restrictive paclitaxel side effect known as paclitaxel-induced peripheral neuropathy (PIPN). A non-pharmacological method called cryotherapy has shown promise in alleviating PIPN-related symptoms. In this systematic review, we aimed to evaluate the safety and effectiveness of cryotherapy in preventing PIPN. The review analyzed four randomized controlled trials (RCTs) involving individuals treated with paclitaxel for breast and gynecological cancer. Cryotherapy showed success in lowering PIPN symptoms in several studies, as judged by various outcome measures, although the findings varied. The safety profile of cryotherapy was typically good, with minimal side effects. However, methodological variations and small sample sizes in the studies analyzed limit drawing definitive conclusions from them. To obtain conclusive evidence, studies with standardized techniques and larger sample sizes are required. Further research is necessary to understand cryotherapy's potential mechanisms and long-term effects. This review highlights the potential of cryotherapy in the management of PIPN, explains how it works, and suggests future research topics to improve its application.
PubMed: 37664355
DOI: 10.7759/cureus.44026