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JCO Clinical Cancer Informatics Sep 2023To explore medications and their administration patterns in real-world patients with breast cancer.
PURPOSE
To explore medications and their administration patterns in real-world patients with breast cancer.
METHODS
A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days between administrations. We explored the first three lines of therapy for patients classified into six groups on the basis of their stage at diagnosis (early as stages I-III late as stage IV) and the sensitivity of the tumor's receptors to targeted therapies: hormone receptor-positive/human epidermal growth factor 2-negative (HR+/-), -positive (+/HR±), or triple-negative (TN; HR-/-). To add credence to the derived regimens, we compared them to the National Comprehensive Cancer Network (NCCN): Breast Cancer (version 2.2023) recommendations.
RESULTS
In early-stage HR+/ and TN groups, the most common regimens were (1) cyclophosphamide and docetaxel, administered once every 3 weeks for three to six cycles and (2) cyclophosphamide and doxorubicin, administered once every 2 weeks for four cycles, followed by paclitaxel administered once every week for 12 cycles. In the early-stage +/HR± group, most patients were administered carboplatin and docetaxel with or without pertuzumab and with trastuzumab (for six or more cycles). Medications most commonly administered in our data set (7,798 patients) agreed with recommendations from the NCCN in terms of medications (regimens), number of administrations (cycles), and days between administrations (cycle length).
CONCLUSION
Although there is a general agreement with the NCCN Guidelines, real-world medication data exhibit variability in the medications and their administration patterns.
Topics: Humans; Female; Breast Neoplasms; Docetaxel; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide
PubMed: 37851942
DOI: 10.1200/CCI.23.00061 -
European Urology Dec 2023In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel...
Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer.
In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Molecular Imaging; Genomics; Castration
PubMed: 37173210
DOI: 10.1016/j.eururo.2023.04.025 -
Journal of Cell Communication and... Sep 2023It is now well-established that an obese condition correlates with a higher risk of prostate cancer (PCa). A crosstalk between adipose tissue and PCa has been observed...
It is now well-established that an obese condition correlates with a higher risk of prostate cancer (PCa). A crosstalk between adipose tissue and PCa has been observed but is still poorly characterized. Herein, we demonstrated that 3T3-L1 adipocyte conditioned media (CM) could endow PC3 and DU145 PCa cells with stemness properties, by stimulating their sphere formation ability and promoting CD133 and CD44 expression. Moreover, after exposure to adipocyte CM both PCa cell lines underwent partial epithelial-to-mesenchymal transition (EMT), with E-/N-cadherin switch and Snail upregulation. Specifically, these changes in PC3 and DU145 cell phenotype were accompanied by increased tumor clonogenic activity and survival, as well as by enhanced invasion, anoikis resistance and matrix metalloproteinase (MMP) production. Finally, adipocyte CM-treated PCa cells exhibited reduced responsiveness to both docetaxel and cabazitaxel, demonstrating greater chemoresistance. Overall, these data indicate that adipose tissue can effectively contribute to PCa aggressiveness by reprogramming the cancer stem cell (CSC) machinery. Adipocytes endow prostate cancer cells with stem-like properties and mesenchymal traits, increasing their tumorigenicity, invasion and chemoresistance.
PubMed: 36940071
DOI: 10.1007/s12079-023-00738-x -
Frontiers in Oncology 2023Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that imposes a major burden on patients and healthcare systems. Three structured literature... (Review)
Review
PURPOSE
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that imposes a major burden on patients and healthcare systems. Three structured literature reviews (treatment guidelines, treatment landscape, and human/clinical/patient burden) and one systematic literature review (economic burden) were conducted to better understand the disease burden and unmet needs for patients with late-stage mCRPC, for whom optimal treatment options are unclear.
METHODS
Embase, MEDLINE, MEDLINE In-Process, the CENTRAL database (structured and systematic reviews), and the Centre for Reviews and Dissemination database (systematic review only) were searched for English-language records from 2009 to 2021 to identify mCRPC treatment guidelines and studies related to the treatment landscape and the humanistic/economic burden of mCRPC in adult men (aged ≥18 years) of any ethnicity.
RESULTS
In total, six records were included for the treatment patterns review, 14 records for humanistic burden, nine records for economic burden, three records (two studies) for efficacy, and eight records for safety. Real-world treatment patterns were broadly aligned with treatment guidelines and provided no optimal treatment sequencing beyond second line other than palliative care. Current post-docetaxel treatments in mCRPC are associated with adverse events that cause relatively high rates of treatment discontinuation or disruption. The humanistic and economic burdens associated with mCRPC are high.
CONCLUSION
The findings highlight a lack of treatment options with novel mechanisms of action and more tolerable safety profiles that satisfy a risk-to-benefit ratio aligned with patient needs and preferences for patients with late-stage mCRPC. Treatment approaches that improve survival and health-related quality of life are needed, ideally while simultaneously reducing costs and healthcare resource utilization.
PubMed: 37829336
DOI: 10.3389/fonc.2023.1240864 -
Scientific Reports Aug 2023Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling...
Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are closely interact with CD147 and revealed that lateral interaction between CD147 and CD276 concealed within the lipid raft microdomain in CSCs, confers resistance to docetaxel, a commonly used chemotherapy agent for various cancer types, including metastatic breast cancer. Moreover, we investigated the clinical relevance of CD147 and CD276 co-expression in HER2+ breast cancer (BC) and triple-negative breast cancer patients who underwent chemotherapy. We observed poor disease-free survival and Overall survival rates in patients of CD147 and CD276 (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis in independent cohorts of HER2+ BC support for the association between co-expression of CD147 and CD276 and a poor response to chemotherapy. Collectively, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may serve as a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of BC stemness.
Topics: Humans; Proteome; Proteomics; Triple Negative Breast Neoplasms; Docetaxel; Membrane Proteins; Transcription Factors; B7 Antigens
PubMed: 37648771
DOI: 10.1038/s41598-023-41416-7 -
BMC Cancer Jul 2023Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The...
Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The combination of gemcitabine and docetaxel has demonstrated its role predominantly in leiomyosarcoma and pleomorphic sarcomas but has not been prospectively studied in SS. This trial assesses the efficacy, tolerability and quality of life (QoL) with this regimen in metastatic/unresectable locally advanced relapsed SS.Patients and methods This was a single-arm, two-stage, phase II, investigator-initiated interventional study among patients with metastatic or unresectable locally advanced SS who had progressed after at least one line of chemotherapy. Gemcitabine 900 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 were administered intravenously every 21 days. The primary endpoint was 3-month progression-free rate (PFR); overall survival (OS), progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL) constituted the secondary endpoints.Results Twenty-two patients were enrolled between March 2020 and September 2021 and the study had to be closed early due to slow accrual. The study population comprised of 18 (81.8%) patients with metastatic disease and 4 (18.2%) patients with locally advanced, unresectable disease. The most common primary sites of disease were extremity in 15 (68%) and the median number of lines of prior therapies received was 1 (range 1-4). 3-month PFR was 45.4% (95% CI 24.8-66.1) and ORR was 4.5%. Median progression-free survival (PFS) was 3 months (95% CI 2.3-3.6) and median OS was 14 months (95% CI 8.9-19.0). 7 (31.8%) patients experienced grade 3 or worse toxicities, including anemia (18%), neutropenia (9%) and mucositis (9%). QoL analysis demonstrated significant decline in certain functional and symptom scales, while financial and global health scales remained stable.Conclusion This is the first prospective study on the combination of gemcitabine and docetaxel performed specifically in patients with advanced, relapsed SS. Although the accrual of patients could not be completed as planned, the therapy did produce clinically meaningful outcomes and met its primary endpoint of 3-month PFR. This result, along with the manageable toxicity profile and stable global health status on QoL analysis, should encourage further studies.Trial registration This trial was prospectively registered under the Clinical Trials Registry of India on 26/02/2020 (Registration number: CTRI/2020/02/023612).
Topics: Humans; Docetaxel; Gemcitabine; Quality of Life; Sarcoma, Synovial; Prospective Studies; Deoxycytidine; Neoplasm Recurrence, Local; Sarcoma; Soft Tissue Neoplasms; Neutropenia; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 37422615
DOI: 10.1186/s12885-023-11099-4 -
Cancers Dec 2023Cervical cancer is associated with persistent Human Papilloma Virus (HPV) infections and is the fourth most common cancer in women worldwide. Current treatment options;... (Review)
Review
Cervical cancer is associated with persistent Human Papilloma Virus (HPV) infections and is the fourth most common cancer in women worldwide. Current treatment options; surgery, chemotherapy, and radiation, are often associated with severe side effects including possible infertility. Novel treatment options are required to help combat this disease and reduce side effects. Many plant-derived chemicals, including paclitaxel and docetaxel, are already in use as treatments for various cancers. Genistein is a polyphenolic isoflavone found in foods including soybeans and legumes, and studies have shown that it has various biological effects and anti-cancer properties. This review aims to summarize the existing studies examining the effects of genistein on cervical cancer. All relevant in vitro and in vivo studies are summarized, and the key findings are highlighted in the associated tables. Based on the available in vitro/cell culture studies reported here, genistein inhibits cervical cancer cell proliferation and induces apoptosis. Use of genistein in combination with radiation or chemotherapy agents resulted in enhanced response indicating radio- and chemo-sensitization properties. More animal studies are required to examine the effectiveness of genistein in vivo. Such studies will form the basis for future human studies exploring the potential of genistein to be used in the treatment of cervical cancer.
PubMed: 38201463
DOI: 10.3390/cancers16010035 -
Frontiers in Pharmacology 2023Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to...
Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to comprehensively assess the efficacy of multiple treatment regimens for mCRPC through a network meta-analysis (NMA) of randomized controlled trials (RCTs). A systematically comprehensive search for randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Embase, and Web of Science databases. The network meta-analysis was employed to compare the overall survival (OS), progression-free survival (PFS), and radiographic progression-free survival (rPFS) among different interventions at specific time points. This study was prospectively registered with PROSPERO (CRD42023422823). A total of 29 RCTs, involving 12,706 patients and investigating 16 interventions, were included in the analysis. Chempretarget ((capivasertib or cabozantinib) + docetaxel + prednisone)) and PARP (Olaparib or rucaparib) inhibitors emerged as interventions that significantly improved survival outcomes compared to first-line treatment in mCRPC patients. Chempretarget demonstrated superior overall survival starting from the 12th month, while PARP inhibitors showed a clear advantage in progression-free survival within the 3-18 months range. Notably, chempre ((Docetaxel or Cabazitaxel) + prednisone) exhibited favorable performance in radiographic progression-free survival during the 3-18 month period. Our findings underscore the efficacy of chempretarget, PARP inhibitors, and chempre in enhancing survival outcomes for mCRPC patients. Further head-to-head comparisons are warranted to validate these results. These findings carry important implications for treatment decision-making in mCRPC and may guide the development of more effective therapeutic strategies.
PubMed: 38074136
DOI: 10.3389/fphar.2023.1290990 -
Alternative Therapies in Health and... Sep 2023We aimed to investigate the clinical efficacy of atezolizumab and docetaxel in the treatment of non-small cell lung cancer (NSCLC) via meta-analysis and systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to investigate the clinical efficacy of atezolizumab and docetaxel in the treatment of non-small cell lung cancer (NSCLC) via meta-analysis and systematic review.
METHODS
Publications were searched from China National Knowledge Infrastructure (CNKI), Chongqing Vipers Chinese Science and Technology Journal database (VIP), Wanfang database, PubMed database, Embase database, Cochrane Library and Web of Science. Randomized controlled trials (RCTs) of atezolizumab and docetaxel in the treatment of patients with NSCLC were collected. The retrieval period was from the establishment of the database to November 2021 and updated on 22 April 2023. According to the inclusion and exclusion criteria, the included studies were screened and quality evaluated. Meta-analysis was performed using RevMan 5.4.3 (Cochrane Training, Summertown, Oxford UK) software.
RESULTS
A total of 6 RCTs were included in our analysis, including 6348 patients with NSCLC. Our results showed that the atezolizumab group had significantly longer overall survival (OS) than the docetaxel group (hazard ratio [HR] = 0.77; 95% CI, 0.73-0.81); P < .00001). In terms of progression-free survival (PFS) and objective response rate (ORR), the atezolizumab group was not significantly superior to the docetaxel group (HR = 0.96; 95% CI, 0.90-1.02; P = .20), (relative ratio [RR] = 1.10, 95% CI, 0.95-1.26; P = .20). In terms of treatment-related adverse events (TRAEs), after treatment, the number of patients with TRAEs in the atezolizumab group was significantly lower than in the docetaxel group (RR = 0.65; 95% CI, 0.54-0.79; P < .00001).
CONCLUSION
Compared with docetaxel, atezolizumab can significantly prolong OS in patients with NSCLC and reduce the occurrence of TRAEs, but there is no advantage in PFS or ORR remission rate. Due to some limitations in case numbers and quality of included studies, multicenter, large sample, high-quality RCTs are still needed for further validation.
Topics: Humans; Docetaxel; Carcinoma, Non-Small-Cell Lung; Treatment Outcome; Lung Neoplasms; Multicenter Studies as Topic
PubMed: 37318886
DOI: No ID Found -
Oral Oncology Dec 2023In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence.
BACKGROUND
In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC.
MATERIALS AND METHODS
Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease. Patients were randomly assigned (1:1) to pembrolizumab 200 mg Q3W or investigator's choice of standards of care (SOC): methotrexate, docetaxel, or cetuximab. Outcomes included OS, PFS, ORR, and DOR. The data cutoff was May 15, 2017.
RESULTS
There were 125 patients (pembrolizumab, 53; SOC, 72) in the recurrent-only subgroup, 204 in the recurrent-metastatic subgroup (pembrolizumab, 108; SOC, 96), and 166 in the metastatic-only subgroup (pembrolizumab, 86; SOC, 80). The hazard ratio (95% CI) for death for pembrolizumab versus SOC was 0.83 (0.55-1.25) in the recurrent-only, 0.78 (0.58-1.06) in the recurrent-metastatic, and 0.74 (0.52-1.05) in the metastatic-only subgroups. PFS was similar between treatment arms in all subgroups. ORR was 22.6% for pembrolizumab versus 16.7% for SOC in the recurrent-only, 10.2% versus 6.3% in the recurrent-metastatic, and 15.1% versus 8.8% in the metastatic-only subgroups. DOR was numerically longer with pembrolizumab in all subgroups.
CONCLUSION
Pembrolizumab provided numerically longer OS and durable responses in all subgroups compared with SOC, suggesting that patients with previously treated R/M HNSCC benefit from pembrolizumab regardless of recurrence pattern.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Cetuximab; Docetaxel; Methotrexate; Platinum; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37925894
DOI: 10.1016/j.oraloncology.2023.106587