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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 -
Acta Oncologica (Stockholm, Sweden) Sep 2023We compared the effectiveness of currently available systemic therapies for high-volume metastatic hormone-sensitive prostate cancer (mHSPC) and aimed to establish the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We compared the effectiveness of currently available systemic therapies for high-volume metastatic hormone-sensitive prostate cancer (mHSPC) and aimed to establish the optimal treatment regimen.
MATERIAL AND METHODS
We searched multiple databases for randomized controlled trials (RCTs) that evaluated the efficacy of systemic therapy in patients with high-volume mHSPC. Bayesian network meta-analysis was used to indirectly compare overall survival (OS) and progression-free survival (PFS) of various systemic therapies.
RESULTS
Eleven RCTs (6708 participants) finally met the eligibility criteria. Compared with androgen deprivation therapy (ADT) alone, rezvilutamide (REZ) [hazard ratio (HR) = 0.58, 95% confidence interval (CI): 0.44-0.77], abiraterone (ABI) (HR = 0.61, 95% CI: 0.53-0.71), apalutamide (APA) (HR = 0.70, 95% CI: 0.56-0.88), enzalutamide (ENZ) (HR = 0.65, 95% CI: 0.53-0.80), docetaxel (DOC) (HR = 0.72, 95% CI: 0.63-0.84), darolutamide (DAR) + DOC (HR = 0.49, 95% CI: 0.39-0.62), and ABI + DOC (HR = 0.52, 95% CI: 0.38-0.71) significantly improved OS in patients with high-volume mHSPC. Compared with DOC, no advantages were observed for doublet therapies, including REZ, ABI, APA, and ENZ on the basis of ADT, whereas DAR + DOC (HR = 0.68, 95% CI: 0.57-0.82) and ABI + DOC (HR = 0.72, 95% CI: 0.55-0.95) was associated with better OS. The ranking analysis showed that triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT) had the greatest improvement in OS, followed by REZ + ADT. All the regimens showed improved PFS in patients with high-volume mHSPC. Compared with DOC, significant differences were detected for DAR + DOC, ABI + DOC, ENZ + DOC, REZ, and ENZ. According to the ranking analysis, triplet therapy ranked first, followed by ENZ and REZ.
CONCLUSIONS
REZ + ADT were the highest ranked doublet therapy for improvement in OS of patients with high-volume mHSPC, second only to triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT).
Topics: Male; Humans; Network Meta-Analysis; Treatment Outcome; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Hormones; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37548225
DOI: 10.1080/0284186X.2023.2241985 -
BJU International Oct 2023To evaluate the efficacy of systemic therapies in patients with worse performance status (PS) treated for high-risk non-metastatic prostate cancer (PCa), metastatic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy of systemic therapies in patients with worse performance status (PS) treated for high-risk non-metastatic prostate cancer (PCa), metastatic hormone-sensitive PCa (mHSPC), and non-metastatic/metastatic castration-resistant PCa (nmCRPC/mCRPC), as there is sparse pooled data showing the effect of PS on oncological outcomes in patients with PCa.
METHODS
Three databases were queried in June 2022 for randomised controlled trials (RCTs) analysing patients with PCa treated with systemic therapy (i.e., adding androgen receptor signalling inhibitor [ARSI] or docetaxel [DOC] to androgen-deprivation therapy [ADT]). We analysed the oncological outcomes of patients with PCa with worse PS, defined as Eastern Cooperative Oncology Group PS ≥ 1, treated with combination therapies and compared these to patients with good PS. The main outcomes of interest were overall survival (OS), metastasis-free survival (MFS), and progression-free survival.
RESULTS
Overall, 25 and 18 RCTs were included for systematic review and meta-analyses/network meta-analyses, respectively. In all clinical settings, combination systemic therapies significantly improved OS in patients with worse PS as well as in those with good PS, while the MFS benefit from ARSI in the nmCRPC setting was more pronounced in patients with good PS than in those with worse PS (P = 0.002). Analysis of treatment ranking in patients with mHSPC revealed that triplet therapy had the highest likelihood of improved OS irrespective of PS; specifically, adding darolutamide to DOC + ADT had the highest likelihood of improved OS in patients with worse PS. Analyses were limited by the small proportion of patients with a PS ≥ 1 (19%-28%) and that the number of PS 2 was rarely reported.
CONCLUSIONS
Among RCTs, novel systemic therapies seem to benefit the OS of patients with PCa irrespective of PS. Our findings suggest that worse PS should not discourage treatment intensification across all disease stages.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37395151
DOI: 10.1111/bju.16106 -
The Journal of Infectious Diseases Nov 2023Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and...
BACKGROUND
Cryptosporidiosis is a significant diarrheal disease in humans and animals. Immunodeficient mice are the primary small animal models, but their high costs and specialized breeding/housing requirements limit in vivo drug testing. Numerous anticryptosporidial lead compounds identified in vitro remain untested in vivo.
METHODS
Cryptosporidium tyzzeri, a natural mouse parasite closely related to Cryptosporidium parvum and Cryptosporidium hominis, was isolated to establish an infection model in immunocompetent mice. The model was validated using classic anticryptosporidial drugs (paromomycin and nitazoxanide) and then employed to assess the efficacy of 3 new leads (vorinostat, docetaxel, and baicalein). An in vitro culture of C. tyzzeri was also developed to complement the animal model.
RESULTS
Chronic C. tyzzeri infection was established in chemically immunosuppressed wild-type mice. Paromomycin (1000 mg/kg/d) and nitazoxanide (100 mg/kg/d) demonstrated efficacy against C. tyzzeri. Vorinostat (30 mg/kg/d), docetaxel (25 mg/kg/d), and baicalein (50 mg/kg/d) were highly effective against C. tyzzeri infection. In vitro, nitazoxanide, vorinostat, docetaxel, and baicalein exhibited low to submicromolar efficacy against C. tyzzeri.
CONCLUSIONS
Novel in vivo and in vitro models have been developed for cost-effective anticryptosporidial drug testing. Vorinostat, docetaxel, and baicalein show potential for repurposing and/or optimization for developing new anticryptosporidial drugs.
Topics: Animals; Mice; Humans; Paromomycin; Cryptosporidiosis; Vorinostat; Antiprotozoal Agents; Docetaxel; Cryptosporidium; Cost-Benefit Analysis; Plant Breeding; Cryptosporidium parvum
PubMed: 37418629
DOI: 10.1093/infdis/jiad243 -
The Journal of Urology Jul 2023
Topics: Humans; Gemcitabine; Docetaxel; Urinary Bladder Neoplasms; Deoxycytidine; Administration, Intravesical; Neoplasm Invasiveness; BCG Vaccine
PubMed: 37000006
DOI: 10.1097/JU.0000000000003438 -
European Urology Oncology Oct 2023Adjuvant treatment with either chemotherapy or bacillus Calmette-Guérin (BCG) is recommended for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer...
Sequential Intravesical Gemcitabine and Docetaxel is an Alternative to Bacillus Calmette-Guérin for the Treatment of Intermediate-risk Non-muscle-invasive Bladder Cancer.
Adjuvant treatment with either chemotherapy or bacillus Calmette-Guérin (BCG) is recommended for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC). In this multi-institutional retrospective review, we evaluated oncological outcomes for 182 patients with IR-NMIBC treated with BCG (n = 100) or intravesical sequential gemcitabine and docetaxel (Gem/Doce; n = 82). Median follow-up was 48.6 mo (interquartile range 24.9-70.9). No patient had a previous diagnosis of high-grade disease. Recurrence rates were similar in the two treatment groups (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.65-1.73; p = 0.8). Results were consistent after adjusting for International Bladder Cancer Group (IBCG) risk subgroups, use of single-instillation postoperative chemotherapy, use of blue light cystoscopy, and receipt of maintenance therapy (HR 0.88, 95% CI 0.47-1.64; p = 0.7). Similarly, there was no difference in the rate of stage/grade progression between the treatment groups (HR 0.66, 95% CI 0.21-2.12; p = 0.5). Rates of progression to muscle-invasive disease/metastasis (2.2%) and cancer-specific mortality (1.7%) were low in the cohort. Our results support the use of Gem/Doce as an alternative to BCG in patients with IR-NMIBC. PATIENT SUMMARY: We compared cancer control outcomes for two different treatments for intermediate-risk non-muscle-invasive bladder cancer. Our results show that a chemotherapy combination of docetaxel and gemcitabine is as effective as the BCG (bacillus Calmette-Guérin) treatment traditionally used for this type of bladder cancer.
Topics: Humans; Administration, Intravesical; BCG Vaccine; Docetaxel; Gemcitabine; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Retrospective Studies
PubMed: 37468392
DOI: 10.1016/j.euo.2023.06.011 -
Cell Death & Disease Feb 2024Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for...
Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
Topics: Humans; Nasopharyngeal Carcinoma; Docetaxel; Nasopharyngeal Neoplasms; Transcription Factors; Drug Resistance, Neoplasm; Fluorouracil; Chemoradiotherapy; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Ubiquitin Thiolesterase
PubMed: 38321024
DOI: 10.1038/s41419-024-06496-x -
Advanced Healthcare Materials Oct 2023Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain to be developed to overcome the current limitations of chemotherapy....
Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain to be developed to overcome the current limitations of chemotherapy. Herein, a cancer cell membrane (CM)-camouflaged and ultrasmall iron oxide nanoparticles (USIO NPs)-loaded polyethylenimine nanogel (NG) system is reported to co-deliver docetaxel (DTX) and CD47 siRNA (siCD47). The prepared co-delivery system exhibits good colloidal stability, biocompatibility, and r relaxivity (1.35 mM s ) and enables redox-responsive release of the loaded DTX in the tumor microenvironment. The NG system realizes homologous targeting delivery of DTX and siCD47 to murine breast cancer cells (4T1 cells) for efficient chemotherapy and gene silencing; thus, inducing immunogenic cell death (ICD) and restoring macrophage phagocytic effect through downregulation of "don't eat me" signals on cancer cells. Likewise, the co-delivery system can also act on macrophages to promote their M1 polarization, which can be combined with DTX-mediated ICD and antibody-mediated immune checkpoint blockade to generate effector T cells for robust chemoimmunotherapy. Further, the USIO NPs-incorporated NG system also allows for magnetic resonance imaging of tumors. The developed biomimetic NG system acting on both cancer cells and macrophages holds a promising potential for macrophage phagocytosis-restored chemoimmunotherapy.
Topics: Mice; Animals; Nanogels; Biomimetics; Polyethyleneimine; Cell Line, Tumor; Docetaxel; Phagocytosis; Macrophages; Magnetic Resonance Imaging; Neoplasms; Immunotherapy; Nanoparticles; Tumor Microenvironment
PubMed: 37470683
DOI: 10.1002/adhm.202300967 -
Bioorganic Chemistry Aug 2023Herein, atropisomeric 8-aryltetrahydroisoquinolines have been synthesized and biologically evaluated. Based on our structure-activity relationship study, a highly...
Herein, atropisomeric 8-aryltetrahydroisoquinolines have been synthesized and biologically evaluated. Based on our structure-activity relationship study, a highly bioactive racemic compound has been produced, and it exhibited high antiproliferative activities against various cancer cell lines, including docetaxel-resistant breast cancer cell lines. Each enantiomer can be synthesized in an enantioselective manner by employing the chiral phosphoric acid-catalyzed atroposelective Pictet-Spengler cyclization. An axially (R)-configured enantiomer showed a higher biological activity compared with the axially (S)-configured enantiomer. Further biological studies suggested that the (R)-enantiomer overcomes docetaxel resistance via the downregulation of signal transducer and activator of transcription 3 activation and consequently induces cellular apoptosis in docetaxel-resistant triple-negative breast cancer cell lines.
Topics: Humans; Docetaxel; Tetrahydroisoquinolines; Triple Negative Breast Neoplasms; Apoptosis; Cell Line, Tumor
PubMed: 37229969
DOI: 10.1016/j.bioorg.2023.106573 -
Clinical Cancer Research : An Official... Sep 2023KRAS-mutated non-small cell lung cancer (NSCLC) is the most common genetically altered subtype of NSCLC, yet targeted therapies remain limited. Multiple studies have...
KRAS-mutated non-small cell lung cancer (NSCLC) is the most common genetically altered subtype of NSCLC, yet targeted therapies remain limited. Multiple studies have investigated combinations of MEK inhibitors with chemotherapy without success. Here we discuss these studies and novel approaches to targeting KRAS-mutated NSCLC. See related article by Gadgeel et al., p. 3641.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Docetaxel; Lung Neoplasms; Proto-Oncogene Proteins p21(ras); Neoplasm Recurrence, Local; Mutation
PubMed: 37466928
DOI: 10.1158/1078-0432.CCR-23-1658