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

ATF4-mediated microRNA-145/HDAC4/p53 axis affects resistance of colorectal cancer cells to 5-fluorouracil by regulating autophagy
ConclusionIn conclusion, ATF4-mediated miR-145 inhibition accelerated autophagy of CRC cells and boosted their resistance to 5-FU via the HDAC4/p53 axis. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 21, 2022 Category: Cancer & Oncology Source Type: research

Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study
ConclusionsThese findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. The constraints of this study and lack of reliable comparisons suggest a hypothesis-generating value of these results. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 18, 2022 Category: Cancer & Oncology Source Type: research

Correction to: Evaluation of the absolute oral bioavailability of the anaplastic lymphoma kinase/c-ROS oncogene 1 kinase inhibitor lorlatinib in healthy participants
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 18, 2022 Category: Cancer & Oncology Source Type: research

Discovery and pharmacological characterization of cetrelimab (JNJ-63723283), an anti –programmed cell death protein-1 (PD-1) antibody, in human cancer models
ConclusionCetrelimab potently inhibits PD-1 in vitro and in vivo, supporting its clinical evaluation. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 17, 2022 Category: Cancer & Oncology Source Type: research