The effect of liver dysfunction on the pharmacokinetic disposition of belinostat and its five metabolites in patients with advanced cancers
AbstractBelinostat was approved in 2014 for the treatment of relapsed or refractory peripheral T-cell lymphoma, however, there was insufficient data to recommend a dose in patients with moderate to severe hepatic impairment. The purpose of this analysis was to characterize the pharmacokinetic disposition of belinostat and its five metabolites in patients with advanced cancers and varying degrees of liver dysfunction. A population pharmacokinetic model was therefore developed to describe the parent-metabolite system. The final model was then implemented to assess the effect of liver impairment on each metabolic pathway of b...
Source: Cancer Chemotherapy and Pharmacology - March 14, 2024 Category: Cancer & Oncology Source Type: research

Phase 2 study of glucarpidase in patients with delayed methotrexate elimination after high-dose methotrexate therapy
ConclusionGlucarpidase showed an effect of reducing plasma MTX concentration in Japanese patients with DME as that observed in a previous US study, confirming its favorable safety and tolerability. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 13, 2024 Category: Cancer & Oncology Source Type: research

Association of VEGFA and CCL4L2 polymorphisms with hand-foot skin reaction and survival of regorafenib in Japanese patients with colorectal cancer
ConclusionsThese VEGF-related polymorphisms were found to be associated with HFSR and the survival benefits of regorafenib treatment.Trial registration number and dateUMIN000013939, registered on May 12, 2014, when 6  months after the approval by the Institutional Review Board of Showa University. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 8, 2024 Category: Cancer & Oncology Source Type: research

Vitamin D suppresses CD133+/CD44  + cancer stem cell stemness by inhibiting NF-κB signaling and reducing NLRP3 expression in triple-negative breast cancer
ConclusionFindings elucidate that VD mediates the modulation of stemness in CD133+/CD44  + breast cancer stem cells through the regulation of NLRP3 expression. The research represents novel insights on the implications for the application of VD in cancer therapies. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 8, 2024 Category: Cancer & Oncology Source Type: research

Impact of loperamide on the pharmacokinetics and tissue disposition of ritonavir-boosted oral docetaxel therapy; a preclinical assessment
ConclusionThese results suggest that delayed loperamide administration can be added to ritonavir-boosted oral docetaxel treatment, without affecting the overall systemic exposure of docetaxel. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 8, 2024 Category: Cancer & Oncology Source Type: research

Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series
ConclusionThis case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 8, 2024 Category: Cancer & Oncology Source Type: research

Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors
ConclusionIn this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations.Clinical trial registration number: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 7, 2024 Category: Cancer & Oncology Source Type: research

Pharmacokinetic and bioequivalence study of two capecitabine tablets in Chinese patients with solid tumor cancer
AbstractCapecitabine (CAP) is one of the fluoropyrimidine deoxynucleoside carbamates, which can be converted to 5-fluorouracil (5-FU) by thymine deoxynucleoside phosphorylase (dThdPase) to exert antitumor effects. The purpose of this study is to compare the pharmacokinetics (PK), bioequivalence (BE), and safety of two CAP tablets in Chinese patients with solid tumor cancer. The results showed that the geometric mean ratios (GMRs) ofCmax, AUC0 −t and AUC0 –∞ of CAP T/R reagent were 90.26%, 95.27%, and 95.07, respectively. The values and 90% confidence intervals (CI) of AUC0 −t, AUC0 –∞, andCmax all fall within t...
Source: Cancer Chemotherapy and Pharmacology - March 7, 2024 Category: Cancer & Oncology Source Type: research

Predictive performance of population pharmacokinetic models of imatinib in chronic myeloid leukemia patients
ConclusionMenon et al. model was able to predict well for our clinical data where it had the relative mean prediction error percentage  ≤ 20%, relative median absolute prediction error ≤ 30% and relative root mean square error close to zero. Based on this final model, we proposed a dosing nomogram for various weight groups, which could potentially help to maintain the trough concentrations in the therapeutic range. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 5, 2024 Category: Cancer & Oncology Source Type: research

Correction to: Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 5, 2024 Category: Cancer & Oncology Source Type: research

Visceral obesity and sarcopenia as predictors of efficacy and hematological toxicity in patients with metastatic breast cancer treated with CDK 4/6 inhibitors
ConclusionThe present study supported the significance of sarcopenia and low visceral adipose tissue as potential early indicators of poor PFS in patients treated with CDK 4/6 inhibitors. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 4, 2024 Category: Cancer & Oncology Source Type: research

Utility and impact of quantitative pharmacology on dose selection and clinical development of immuno-oncology therapy
AbstractImmuno-oncology (IO) therapies have changed the cancer treatment landscape. Immune checkpoint inhibitors (ICIs) have improved overall survival in 20 –40% of patients with malignancies that were previously refractory. Due to the uniqueness in biology, modalities and patient responses, drug development strategies for IO differed from that traditionally used for cytotoxic and target therapies in oncology, and quantitative pharmacology utilizing m odeling approach can be applied in all phases of the development process. In this review, we used case studies to showcase how various modeling methodologies were applied f...
Source: Cancer Chemotherapy and Pharmacology - March 2, 2024 Category: Cancer & Oncology Source Type: research

Successful use of Palbociclib combined with Venetoclax and Azacitidine in an adult with refractory/relapsed therapy-related acute myeloid leukemia
ConclusionsAlthough only one successful case is presented here, three-drug combination regimens should be considered as another treatment option for t-AML in the future. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 2, 2024 Category: Cancer & Oncology Source Type: research

Impact of bariatric surgery on oral anticancer drugs: an analysis of real-world data
ConclusionsThe proposed flowchart can support optimizing the treatment with orally administered anticancer drugs in patients who underwent bariatric surgery. We recommend performing TDM in drugs that belong to BCS classes II, III, or IV. If more risk factors are present in BCS classes II or IV, a priori switches to other drugs may be advised. In specific cases, higher dosages can be provided from the start (e.g., tamoxifen). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 1, 2024 Category: Cancer & Oncology Source Type: research

Ommaya reservoir use in pediatric ALL and NHL: a review at St. Jude Children ’s Research Hospital
ConclusionsOmR were able to be safely placed and administer intraventricular methotrexate with and without boost doses in patients from 7 days to 22 years old. Boosting strategies are predicted to increase CSF methotrexate concentrations  ≥ 1 µM for 72 h. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 28, 2024 Category: Cancer & Oncology Source Type: research