Cancer Chemotherapy and Pharmacology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Elimination of tucatinib, a small molecule kinase inhibitor of HER2, is primarily governed by CYP2C8 enantioselective oxidation of gem-dimethyl
ConclusionCYP2C8 and CYP3A4/5 are the primary drug-metabolizing enzymes involved in the in vitro metabolism of tucatinib, which provided the basis to describe human disposition of tucatinib and formation of the observed metabolites. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 18, 2022 Category: Cancer & Oncology Source Type: research

A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer
ConclusionsContinuous veliparib is safe and tolerable. The RP2D was 400  mg BID. There is evidence of clinical activity of veliparib in patients withBRCAmut andBRCAwt cancers. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 18, 2022 Category: Cancer & Oncology Source Type: research

Assessment of cytochrome P450 3A4-mediated drug –drug interactions for ipatasertib using a fit-for-purpose physiologically based pharmacokinetic model
ConclusionThis study demonstrates the value of using a fit-for-purpose PBPK model to assess the clinical DDIs for ipatasertib and to provide dosing strategies for the concurrent use of other CYP3A4 perpetrators or victims. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 15, 2022 Category: Cancer & Oncology Source Type: research

Is age just a number? A population pharmacokinetic study of gemcitabine
ConclusionAge was not of influence on the pharmacokinetics of gemcitabine or its metabolite, dFdU. Age-related dose adjustments for gemcitabine based on pharmacokinetic considerations are not recommended.Trial registration numberNL39647.048.12, registered on May 3rd 2012. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 15, 2022 Category: Cancer & Oncology Source Type: research

An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer
ConclusionCollectively, our results suggest that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 13, 2022 Category: Cancer & Oncology Source Type: research

Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors
ConclusionThe PPK model adequately described rucaparib PK, and none of the covariates evaluated had a clinically relevant effect.ClinicalTrials.govStudy 1014 (NCT01009190), Study 10 (NCT01482715), ARIEL2 (NCT01891344), ARIEL3 (NCT01968213), and TRITON2 (NCT02952534). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 10, 2022 Category: Cancer & Oncology Source Type: research

Population pharmacokinetic analysis of tepotinib, an oral MET kinase inhibitor, including data from the VISION study
ConclusionsTepotinib shows dose proportionality up to at least the therapeutic dose, and time-independent clearance with a profile appropriate for once-daily dosing. None of the covariates identified had a clinically meaningful effect on tepotinib exposure or required dose adjustments. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 6, 2022 Category: Cancer & Oncology Source Type: research

PDI inhibitor LTI6426 enhances panobinostat efficacy in preclinical models of multiple myeloma
AbstractThe histone deacetylase inhibitor (HDACi), panobinostat (Pano), is approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of relapsed/refractory multiple myeloma (MM). Despite regulatory approvals, Pano is used on a limited basis in MM due largely to an unfavorable toxicity profile. The MM treatment landscape continues to evolve, and for Pano to maintain a place in that paradigm it will be necessary to identify treatment regimens that optimize its effectiveness, particularly those that permit dose reductions to eliminate unwanted toxicity. Here, we propose...
Source: Cancer Chemotherapy and Pharmacology - April 5, 2022 Category: Cancer & Oncology Source Type: research

Editorial Expression of Concern for: Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 5, 2022 Category: Cancer & Oncology Source Type: research

Efficacy and safety exposure –response relationships of apalutamide in patients with metastatic castration-sensitive prostate cancer: results from the phase 3 TITAN study
ConclusionsDifferences in apalutamide exposure were not associated with clinically relevant differences in rPFS or OS in patients with mCSPC. Patients with increased apalutamide exposure are more likely to develop skin rash and pruritus. Dose reductions may improve these adverse events, based on an individual risk –benefit approach. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 2, 2022 Category: Cancer & Oncology Source Type: research

Lurbinectedin-induced thrombocytopenia: the role of body surface area
AbstractLurbinectedin is an alkylating agent approved for the second-line treatment of small cell lung cancer. Although initial studies showed no association between body surface area (BSA) and drug clearance, the recommended dose is 3.2  mg/m2 every 3 weeks. This recommendation was based on an exposure –response study, which demonstrated that patients with lower BSA had a higher incidence of thrombocytopenia. Herein we present the factors associated with BSA and thrombopoiesis, which may have contributed to the observed relationship. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 1, 2022 Category: Cancer & Oncology Source Type: research

Pharmacokinetics of metronomic temozolomide in cerebrospinal fluid of children with malignant central nervous system tumors
ConclusionMetronomic oral temozolomide penetrates into the CSF in pediatric patients, with even higher concentration levels compared to adults. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 30, 2022 Category: Cancer & Oncology Source Type: research

Anti-drug antibodies in the current management of cancer
AbstractMonoclonal antibodies (mAbs) have become one of the main therapeutic weapons in modern oncology, mainly as targeted therapies, and immune checkpoint inhibitors. The generation of anti-drug antibodies (ADAs) after their administration can alter their pharmacokinetic, pharmacodynamic, efficacy and safety profile causing infusion-related reactions. Several risk factors have been associated with ADAs development, notably host genetics and immune status, comorbidity, concomitant medications, mAbs molecular structure, dose and route of administration. ADAs are not usually tested on daily clinical practice, being their an...
Source: Cancer Chemotherapy and Pharmacology - March 25, 2022 Category: Cancer & Oncology Source Type: research

A phase I pharmacokinetic study of copanlisib in Chinese patients with relapsed indolent non-Hodgkin lymphoma
ConclusionsCopanlisib was well tolerated in Chinese patients with relapsed or refractory iNHL at the dose of 60  mg and demonstrated encouraging disease control, thus warranting further clinical investigation.Clinical trial registration numberNCT03498430 (April 13, 2018). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 23, 2022 Category: Cancer & Oncology Source Type: research

Relationship between achievement of major molecular response or deep molecular response and nilotinib plasma concentration in patients with chronic myeloid leukemia receiving first-line nilotinib therapy
ConclusionFor patients with newly diagnosed CML, the nilotinib dose may be adjusted using aCtrough of above 619  ng/mL as the minimum effective concentration, i.e., the lowest concentration required for MMR or DMR achievement within a shorter time, during early stages after beginning therapy to obtain faster and deeper clinical responses. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 22, 2022 Category: Cancer & Oncology Source Type: research