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A bavachinin analog, D36, induces cell death by targeting both autophagy and apoptosis pathway in acute myeloid leukemia cells
ConclusionThis study suggests that D36 is a promising small-molecule for the treatment of acute myeloid leukemia. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 12, 2022 Category: Cancer & Oncology Source Type: research

An update on antibody –drug conjugates in urothelial carcinoma: state of the art strategies and what comes next
AbstractIn recent years, considerable progress has been made in increasing the knowledge of tumour biology and drug resistance mechanisms in urothelial cancer. Therapeutic strategies have significantly advanced with the introduction of novel approaches such as immune checkpoint inhibitors and Fibroblast Growth Factor Receptor inhibitors. However, despite these novel agents, advanced urothelial cancer is often still progressive in spite of treatment and correlates with a poor prognosis. The introduction of antibody –drug conjugates consisting of a target-specific monoclonal antibody covalently linked to a payload (cytotox...
Source: Cancer Chemotherapy and Pharmacology - August 11, 2022 Category: Cancer & Oncology Source Type: research

Paclitaxel exposure-toxicity analysis reveals a pharmacokinetic determinant for dose-limiting neutropenia in East-Asian solid tumor patients: results from two prospective, phase II studies
ConclusionPatients with PTX Tc  >  0.05 duration above 39 h experience more severe neutropenia than those under 39 h. Prospective studies are needed to verify this threshold. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 3, 2022 Category: Cancer & Oncology Source Type: research

Optimized scaling of translational factors in oncology: from xenografts to RECIST
ConclusionsWe believe that given more data, our methodology could contribute to increasing the translational capabilities of TGI models. More specifically, an appropriate translational method could be developed for drugs with the same mechanism of action, which would allow for all preclinical data to be leveraged for new drugs of the same class. This would ensure that fewer clinically inefficacious drugs are tested in clinical trials. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - August 3, 2022 Category: Cancer & Oncology Source Type: research

A phase I dose escalation, dose expansion and pharmacokinetic trial of gemcitabine and alisertib in advanced solid tumors and pancreatic cancer
ConclusionsThis trial established the recommended phase 2 dose of alisertib 50  mg to be combined with gemcitabine. Gemcitabine and alisertib are a feasible strategy with potential for disease control in multiple heavily pre-treated tumors, though gastrointestinal and hematologic toxicity was apparent. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 30, 2022 Category: Cancer & Oncology Source Type: research

A dose regimen-finding study to evaluate the safety, tolerability, pharmacokinetics, and activity of oratecan in subjects with advanced malignancies
ConclusionsThe MTD of oratecan was encequidar methanesulfonate 15  mg plus irinotecan 280 mg/m2. Exposure for irinotecan and SN-38 increased with increased dose. Potential antitumor activity was observed at the 280 and 320  mg/m2 dose levels. The safety profile of oratecan was comparable to that of intravenous irinotecan. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 29, 2022 Category: Cancer & Oncology Source Type: research

Mouse pharmacokinetics and metabolism of the phenylurea thiocarbamate NSC 161128
ConclusionsAn analytical LC –MS/MS method was successfully developed for the detection and quantification of NSC 161128 and its metabolites. These results increase the understanding of NSC 161128 pharmacokinetic and metabolic properties. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 27, 2022 Category: Cancer & Oncology Source Type: research

Revisiting metronomic vinorelbine with mathematical modelling: a Phase I trial in lung cancer
ConclusionsMOV was characterized by important variability in drug exposure among patients. However, and despite being all heavily pre-treated, 73% of disease control rate and 11 weeks PFS were achieved with manageable toxicities. PK/PD relationships yielded conflicting results depending on the initial tumor burden and BSA, suggesting that patients should be carefully selected prior to be scheduled for metronomic regimen. Possible role NLR could play as a predictive marker suggests immunomodulating features with MOV. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 22, 2022 Category: Cancer & Oncology Source Type: research

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small cell lung cancer: exposure –response relationship
ConclusionsNo association was observed between RAM exposure and response, suggesting that the RELAY regimen of RAM 10  mg/kg Q2W with ERL is an optimized, efficacious, and safe first-line treatment for patients with untreated, metastatic, EGFR-mutated NSCLC.Trial registration: ClinicalTrials.gov, NCT02411448. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 16, 2022 Category: Cancer & Oncology Source Type: research

Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400  mg
ConclusionThe two-compartment transit model adequately describes the absorption and distribution of imatinib in healthy volunteers. For patients, a lower clearance of imatinib compared to healthy volunteer was estimated by the model. The model can be applied for dose individualization based on trough concentrations assuming no significant differences in absorption between patients and healthy volunteers. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 14, 2022 Category: Cancer & Oncology Source Type: research

Prospective evaluation of the relationship between response and exposure of total and unbound erlotinib in non-small cell lung cancer patients
ConclusionThe lack of relationship between efficacy and exposure of total and unbound erlotinib demonstrates that the standard dose of 150  mg/day is sufficient for the treatment of NSCLC harboringEGFR-activating mutations, despite wide inter-individual variability in exposure and dose reduction.Clinical trials registration number: UMIN000012862. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 12, 2022 Category: Cancer & Oncology Source Type: research

Ex-vivo activation of a liposomal prodrug of mitomycin C by human tumors
ConclusionsTumor tissue homogenates activate MLP with greater efficiency than the surrounding normal tissues, but far less than liver and adipose tissue. These observations demonstrate the bioavailability of liposomal MLP in human tumors, and its pharmacologic potential in cancer therapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 8, 2022 Category: Cancer & Oncology Source Type: research

Development of a population pharmacokinetic/pharmacodynamic model for various oral paclitaxel formulations co-administered with ritonavir and thrombospondin-1 based on data from early phase clinical studies
ConclusionThe developed pharmacokinetic model adequately described the paclitaxel plasma concentrations for the different oral formulations co-administered with ritonavir. This model, and the established pharmacokinetic/pharmacodynamic relationship with TSP-1, may facilitate future development of oral paclitaxel. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 7, 2022 Category: Cancer & Oncology Source Type: research

A phase I/II study of 10-min dosing of bendamustine hydrochloride (rapid infusion formulation) in patients with previously untreated indolent B-cell non-Hodgkin lymphoma, mantle cell lymphoma, or relapsed/refractory diffuse large B-cell lymphoma in Japan
ConclusionsThis study showed that bendamustine is safe, well-tolerated and effective for patients with previously untreated iNHL, MCL or rrDLBCL. Pharmacokinetic data were equivalent to those obtained outside of Japan.Registration numbersRegistration NCT03900377; registered April 3, 2019. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - July 7, 2022 Category: Cancer & Oncology Source Type: research

Exposure –response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations
ConclusionsThese analyses provide important quantitative pharmacologic support for benefit/risk assessment of the 500  mg/day dosage of tepotinib as being appropriate for the treatment of NSCLC harboringMETex14 skipping alterations.Registration NumbersNCT01014936, NCT01832506, NCT01988493, NCT02115373, NCT02864992. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - June 30, 2022 Category: Cancer & Oncology Source Type: research