Adaptive dosing of sunitinib in a metastatic renal cell carcinoma patient: when in silico modeling helps to go quicker to the point
Conclusions and discussionThis case suggests that model-based adaptive dosing could have allowed to reach quicker the best dosing with Sunitinib, thus possibly ensuring a better management of this patient. Model-informed dosing should be used instead of empirical search for the most appropriate dosing to ensure a good benefit/risk ratio with Sunitinib, especially in the context of such aggressive disease. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 11, 2022 Category: Cancer & Oncology Source Type: research

A phase I study of AZD2171 and Temsirolimus in patients with advanced gynecological malignancies
ConclusionsDespite a conservative dose escalation, the toxicity data demonstrated that the combination of AZD2171 and Temsirolimus was not tolerable. Increased awareness of novel toxicities, pharmacological interactions, coupled with strict patient selection and early mitigation of side effects may enhance phase I clinical trial development. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 10, 2022 Category: Cancer & Oncology Source Type: research

Somatic nuclear auto-antigenic sperm protein sensitizes human breast cancer cells to 5-Fluorouracil
ConclusionOur findings suggest sNASP is a novel molecular target having potential to overcome the resistance to 5-FU in breast cancer cells. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 8, 2022 Category: Cancer & Oncology Source Type: research

Pharmacokinetics and pharmacodynamics of MEDI0680, a fully human anti-PD-1 monoclonal antibody, in patients with advanced malignancies
AbstractMEDI0680 is a humanized immunoglobulin monoclonal antibody that targets human programmed cell death protein 1 (PD-1) for the treatment of cancer. A population two-compartmental pharmacokinetic (PK) model and a sequential direct maximal effective drug concentration receptor occupancy (RO) model with baseline parameters were developed to quantify PK variability, identify significant covariates, and characterize the relationship between the PK and the RO of MEDI0680. A total of 58 patients with advanced malignancies received MEDI0680 by intravenous infusion at a dose of 0.1 –20 mg/kg in a phase 1 study. The clearan...
Source: Cancer Chemotherapy and Pharmacology - February 8, 2022 Category: Cancer & Oncology Source Type: research

Efficacy and safety exposure –response analyses of entrectinib in patients with advanced or metastatic solid tumors
ConclusionThese analyses supported that entrectinib at 600  mg/day provides an acceptable benefit–risk ratio in adults withNTRK-,ROS1-, orALK-positive tumors, considered as rare disease. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 3, 2022 Category: Cancer & Oncology Source Type: research

The effects of pazopanib on doxorubicin pharmacokinetics in children and adults with non-rhabdomyosarcoma soft tissue sarcoma: a report from Children ’s Oncology Group and NRG Oncology study ARST1321
ConclusionThe PK data of seven patients treated on ARST1321 is consistent with previously reported population and post hoc doxorubicin clearance and doxorubicinol apparent clearance estimates, showing that the addition of pazopanib does not significantly alter doxorubicin pharmacokinetics. These data support the safety of administration of pazopanib with doxorubicin-containing chemotherapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 27, 2022 Category: Cancer & Oncology Source Type: research

Effects of cyclophosphamide related genetic variants on clinical outcomes of adult hematopoietic cell transplant patients
ConclusionThe present study suggests that genetic variants influencing the PKPD of CY may help identify patients at risk for inferior outcomes after HCT using CY-based reduced-intensity conditioning. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 27, 2022 Category: Cancer & Oncology Source Type: research

Differential tumor inhibitory effects induced by HER3 extracellular subdomain-specific mouse monoclonal antibodies
ConclusionSome of the anti-HER3 MAbs produced in this study displayed tumor inhibitory function and may be considered promising candidates for future HER3-targeted cancer therapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 26, 2022 Category: Cancer & Oncology Source Type: research

Correlation between pharmacokinetic parameters of 5-fluorouracil and related metabolites and adverse reactions in East-Asian patients with advanced colorectal cancer
ConclusionsThere are obvious individual differences in AUC values in CRC patients receiving different dosages of 5-FU based on BSA. The ideal AUC range of 5-FU is 18.23 –29.17 mg·h/L. There was a significant correlation between 5-FUH2 and FABL plasma concentration and adverse reactions. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 24, 2022 Category: Cancer & Oncology Source Type: research

Repurposed antipsychotic chlorpromazine inhibits colorectal cancer and pulmonary metastasis by inducing G2/M cell cycle arrest, apoptosis, and autophagy
ConclusionThese findings indicated that repurposing CPZ is a novel treatment strategy for CRC patients. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 24, 2022 Category: Cancer & Oncology Source Type: research

Curcumin sensitizes response to cytarabine in acute myeloid leukemia by regulating intestinal microbiota
ConclusionCurcumin sensitizes response to Ara-C through regulating microbiota, highlighting the importance of intestinal intact strengthening in chemoresistant therapy. Moreover, aiming at cholesterol synthesis is promising in AML treatment. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 23, 2022 Category: Cancer & Oncology Source Type: research

Roles of DNA polymerase ζ in the radiotherapy sensitivity and oxidative stress of lung cancer cells
DiscussionOur results provided a theoretical basis for targeting DNA polymerase ζ to improve the radiosensitivity of the lung cancer cells to radiotherapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 23, 2022 Category: Cancer & Oncology Source Type: research

Phase I/Ib study of crenolanib with ramucirumab and paclitaxel as second-line therapy for advanced esophagogastric adenocarcinoma
ConclusionsThe addition of crenolanib to paclitaxel/ramucirumab is safe and well-tolerated at a dose level up to 100  mg BID.Clinical trial registrationNCT03193918. June 19, 2017. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 23, 2022 Category: Cancer & Oncology Source Type: research

Dose-dependent bioavailability and tissue distribution of the ATR inhibitor AZD6738 (ceralasertib) in mice
ConclusionThe complex non-linear behavior of AZD6738 PK in mice was due to pre-systemic saturation and which appears to be recapitulated clinically at low doses. PK reported here will allow future correlation of tissue related toxicities with drug exposure as well as exposure with immunological responses. These results can also be compared with those from similar studies of other ATRi to contrast drug exposure with responses. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 23, 2022 Category: Cancer & Oncology Source Type: research

Unintentional combining enzalutamide with a moderate CYP2C8 inhibitor in a patient with metastatic castration-resistant prostate cancer: a case report
ConclusionThis case report shows that enzalutamide can be safely prescribed while cotreated with a moderate CYP2C8-inhibitor, without reducing the dose. More research is warranted to make a statement about the effect of enzalutamide on clopidogrel. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 21, 2022 Category: Cancer & Oncology Source Type: research