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PloS One 2024Xuebijing injection (XBJ) is a commonly used herbal medicine injection in China. However, the physical compatibility of XBJ with other intravenous drugs remains unclear....
OBJECTIVE
Xuebijing injection (XBJ) is a commonly used herbal medicine injection in China. However, the physical compatibility of XBJ with other intravenous drugs remains unclear. The purpose of this research is to evaluate physical compatibility of Xuebijing injection (XBJ) with 53 intravenous drugs (including 31 Chinese medicine injections and 22 chemicals) during simulated Y-site administration.
METHODS
Y-site administration was simulated in vitro by admixing 0.33 ml/ml XBJ with an equal volume of other diluted 53 intravenous drugs, respectively. Physical compatibility including visual inspection, Tyndall beam, particle limits, turbidity, pH, chromacity value, spectroscopic absorption of 550 nm and 420 nm (A550 nm and A420 nm) were observed and assessed at 0, 1, 2, and 4 h. Physical compatibility was defined as all solutions with no color changes, no gas evolution, particulate formation and no Tyndall beam within 4 hours, turbidity changes <0.5 nephelometric turbidity unit (NTU) compared to 0 h, particle limits allowed by the Chinese Pharmacopoeia (Ch.P) 2020 edition, pH changes <10% compared to 0, chromacity value changes <200 compared to 0 h, or photometrical changes of A420 nm <0.0400 or A550 nm <0.0100 compared to 0 h.
RESULTS
XBJ was physically incompatible with 27 of the 53 intravenous drugs tested, 26 were compatible with XBJ for 4 h.
CONCLUSIONS
XBJ should not be simultaneously co-administered with 27 of the 53 intravenous drugs during simulated Y-site. If coadministration was inevitable, flushing tube with NS or D5W before and after infusion of XBJ was needed. Assessment included visual inspection, Tyndall beam, turbidity measurement, particle counts, pH measurement, chromacity value measurement and absorption of A550 nm were proved to be valid and robust for the quality control of infusion and compatibility of Chinese herbal injection.
Topics: Anti-Bacterial Agents; Infusions, Intravenous; Drugs, Chinese Herbal; Injections, Intravenous; Etoposide
PubMed: 38517862
DOI: 10.1371/journal.pone.0299694 -
Physica Medica : PM : An International... Apr 2024In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with...
Using the gamma-index analysis for inter-fractional comparison of in-beam PET images for head-and-neck treatment monitoring in proton therapy: A Monte Carlo simulation study.
GOAL
In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes.
METHODS/MATERIALS
We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans.
RESULTS
Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields.
CONCLUSION
The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course.
Topics: Humans; Proton Therapy; Monte Carlo Method; Positron-Emission Tomography; Tomography, X-Ray Computed; Computer Simulation; Etoposide; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 38492331
DOI: 10.1016/j.ejmp.2024.103329 -
Molecules (Basel, Switzerland) Feb 2024Monitoring etoposide is important due to its wide usage in anti-tumor therapy; however, the commonly used HPLC method is expensive and often requires complicated...
Monitoring etoposide is important due to its wide usage in anti-tumor therapy; however, the commonly used HPLC method is expensive and often requires complicated extraction and detection procedures. Electrochemical analysis has great application prospects because of its rapid response and high specificity, sensitivity, and efficiency with low cost and high convenience. In this study, we constructed a nanoporous gold (NPG)-modified GCE for the detection of etoposide. The electrochemical oxidation of etoposide by NPG caused a sensitive current peak at +0.27 V with good reproductivity in 50 mM of phosphate buffer (pH 7.4). The relationship between etoposide concentration and peak current was linear in the range between 0.1 and 20 μM and between 20 and 150 μM, with a detection sensitivity of 681.8 μA mM cm and 197.2 μA mM cm, respectively, and a limit of detection (LOD) reaching 20 nM. The electrode had a good anti-interference ability to several common anions and cations. Spiked recovery tests in serum, urine, and fermentation broth verified the excellent performance of the sensor in terms of sensitivity, reproducibility, and specificity. This may provide a promising tool for the detection of etoposide in biological samples.
Topics: Nanopores; Etoposide; Gold; Reproducibility of Results; Electrochemical Techniques; Electrodes; Antineoplastic Agents
PubMed: 38474572
DOI: 10.3390/molecules29051060 -
CNS Oncology Jun 2024Adult medulloblastomas (MB) are rare, and optimal post-craniospinal irradiation (CSI) chemotherapy is not yet defined. We investigated hematological toxicity in...
Adult medulloblastomas (MB) are rare, and optimal post-craniospinal irradiation (CSI) chemotherapy is not yet defined. We investigated hematological toxicity in patients treated with platinum-etoposide (EP) post-CSI. Retrospective, single-institution study to determine hematological toxicity in adult MB patients treated with EP (1995-2022). Thirteen patients with a median follow-up of 50 months (range, 10-233) were analyzed. Four discontinued treatment due to toxicity, one after 1, 3 after 3 cycles. Hematological toxicities included grade 3 (5 patients) and grade 4 (6 patients). Two patients experienced post-treatment progression and died 16 and 37 months from diagnosis. Post-CSI EP demonstrates acceptable hematological toxicity in adult MB. However, the small cohort precludes definitive survival outcome conclusions. Prospective studies for comprehensive comparisons with other regimens are needed in this context.
Topics: Humans; Male; Retrospective Studies; Adult; Female; Medulloblastoma; Etoposide; Young Adult; Middle Aged; Cerebellar Neoplasms; Hematologic Diseases; Antineoplastic Combined Chemotherapy Protocols; Follow-Up Studies; Adolescent; Craniospinal Irradiation; Platinum
PubMed: 38456492
DOI: 10.2217/cns-2023-0029 -
The Journal of Clinical Investigation Mar 2024Development of effective strategies to manage the inevitable acquired resistance to osimertinib, a third-generation EGFR inhibitor for the treatment of EGFR-mutant...
Development of effective strategies to manage the inevitable acquired resistance to osimertinib, a third-generation EGFR inhibitor for the treatment of EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), is urgently needed. This study reports that DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide, synergistically decreased cell survival, with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells; suppressed the growth of osimertinib-resistant tumors; and delayed the emergence of osimertinib-acquired resistance. Mechanistically, osimertinib decreased Topo IIα levels in EGFRm NSCLC cells by facilitating FBXW7-mediated proteasomal degradation, resulting in induction of DNA damage; these effects were lost in osimertinib-resistant cell lines that possess elevated levels of Topo IIα. Increased Topo IIα levels were also detected in the majority of tissue samples from patients with NSCLC after relapse from EGFR tyrosine kinase inhibitor treatment. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their susceptibility to osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.
Topics: Humans; Acrylamides; Carcinoma, Non-Small-Cell Lung; Aniline Compounds; ErbB Receptors; Lung Neoplasms; DNA Topoisomerases, Type II; Cell Line, Tumor; Topoisomerase II Inhibitors; Drug Resistance, Neoplasm; Animals; Mice; Mutation; Poly-ADP-Ribose Binding Proteins; Drug Synergism; DNA Damage; Piperazines; Etoposide; Xenograft Model Antitumor Assays
PubMed: 38451729
DOI: 10.1172/JCI172716 -
Environmental Monitoring and Assessment Mar 2024Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal...
Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal aquatic systems, is often difficult and complex. In this study, 70 compounds representing several classes of pharmaceuticals, including antibiotics, anti-inflammatories, insect repellant, antibacterial, antidepressants, chemotherapy drugs, and X-ray contrast media compounds, were found in dreissenid mussel (zebra/quagga; Dreissena spp.) tissue samples. Overall concentration and detection frequencies varied significantly among sampling locations, site land-use categories, and sites sampled proximate and downstream of point source discharge. Verapamil, triclocarban, etoposide, citalopram, diphenhydramine, sertraline, amitriptyline, and DEET (N,N-diethyl-meta-toluamide) comprised the most ubiquitous PPCPs (> 50%) detected in dreissenid mussels. Among those compounds quantified in mussel tissue, sertraline, metformin, methylprednisolone, hydrocortisone, 1,7-dimethylxanthine, theophylline, zidovudine, prednisone, clonidine, 2-hydroxy-ibuprofen, iopamidol, and melphalan were detected at concentrations up to 475 ng/g (wet weight). Antihypertensives, antibiotics, and antidepressants accounted for the majority of the compounds quantified in mussel tissue. The results showed that PPCPs quantified in dreissenid mussels are occurring as complex mixtures, with 4 to 28 compounds detected at one or more sampling locations. The magnitude and composition of PPCPs detected were highest for sites not influenced by either WWTP or CSO discharge (i.e., non-WWTPs), strongly supporting non-point sources as important drivers and pathways for PPCPs detected in this study. As these compounds are detected at inshore and offshore locations, the findings of this study indicate that their persistence and potential risks are largely unknown, thus warranting further assessment and prioritization of these emerging contaminants in the Great Lakes Basin.
Topics: Animals; Sertraline; Lakes; Environmental Monitoring; Bivalvia; Anti-Bacterial Agents; Etoposide; Cosmetics; Antidepressive Agents; Pharmaceutical Preparations
PubMed: 38438687
DOI: 10.1007/s10661-023-12119-3 -
Thoracic Cancer Apr 2024Consolidative thoracic radiotherapy (cTRT) has previously shown benefit to patients with extensive stage small cell lung cancer (ES-SCLC) who respond to chemotherapy....
BACKGROUND
Consolidative thoracic radiotherapy (cTRT) has previously shown benefit to patients with extensive stage small cell lung cancer (ES-SCLC) who respond to chemotherapy. However, the optimum dose of cTRT is unknown. The purpose of this randomized trial is to compare the efficacy of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC.
METHODS
This phase III, multicenter, randomized trial is designed to evaluate the safety and efficacy of different cTRT dose in ES-SCLC. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions (standard dose) or 45 Gy in 15 fractions (high dose) cTRT. The primary endpoint is 2-year overall survival (OS). Secondary endpoints include 2-year progression-free survival (PFS), 2-year local control (LC) and treatment related toxicity as measured by adverse events according to the Common Terminology Criteria for Adverse Events (version 4.0).
DISCUSSION
The present study is the first randomized phase III trial designed to evaluate the efficacy of higher versus lower dose cTRT in ES-SCLC, providing evidence for future clinical practice in prolonging survival of patients with ES-SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Progression-Free Survival; Radiation Dosage; Etoposide; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 38426233
DOI: 10.1111/1759-7714.15263 -
Journal of Clinical and Experimental... Mar 2024We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for...
We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.
Topics: Male; Humans; Aged; Lymphoma, T-Cell, Peripheral; Etoposide; Melphalan; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Leukemia, Myeloid, Acute; Dexamethasone; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation; Treatment Outcome; Combined Modality Therapy
PubMed: 38417872
DOI: 10.3960/jslrt.23054 -
Radiation Oncology (London, England) Feb 2024Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage...
Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy: a propensity score matched multicentre retrospective analysis.
BACKGROUND
Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT).
METHODS
Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects.
RESULTS
A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis.
CONCLUSION
Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients.
Topics: Humans; Lung Neoplasms; Etoposide; Retrospective Studies; Propensity Score; Platinum; Small Cell Lung Carcinoma; Immunotherapy
PubMed: 38413988
DOI: 10.1186/s13014-024-02420-x -
Medicine Feb 2024Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory...
Therapeutic efficacy of high-dose chemotherapy with autologous stem-cell transplantation in 44 relapsed or refractory germ-cell tumor patients: A retrospective cohort study.
Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.
Topics: Humans; Male; Adult; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Neoplasms, Germ Cell and Embryonal; Paclitaxel; Transplantation, Autologous; Etoposide; Salvage Therapy
PubMed: 38394499
DOI: 10.1097/MD.0000000000037213