Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway
ConclusionsThese observations indicate that brusatol is a promising antitumor drug candidate or a supplement to current chemotherapeutic therapies to treat NPC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 24, 2020 Category: Cancer & Oncology Source Type: research

Pharmacokinetics and tolerability of fedratinib, an oral, selective Janus kinase 2 inhibitor, in subjects with renal or hepatic impairment
ConclusionMild RI and HI do not necessitate fedratinib dosage adjustments. Subjects with moderate RI should be monitored (with dosage adjustments made as necessary), whereas those with severe RI should receive a daily dose of 200  mg, reduced from the indicated dose of 400 mg. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 24, 2020 Category: Cancer & Oncology Source Type: research

A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors
ConclusionResults of this phase I trial suggest that PG-11047 can be safely administered to patients on the once weekly dosing schedule described. The manageable toxicity profile and high MTD determination provide a safety profile for further clinical studies, including those in combination with current chemotherapeutic agents. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 23, 2020 Category: Cancer & Oncology Source Type: research

MEK inhibition overcomes everolimus resistance in gastric cancer
ConclusionsInhibition of mTOR pathway can induce “paradoxical” activation of ERK in gastric cancer, and this activation can be reversed by trametinib. Since both drugs are clinically available, our findings might accelerate the initiation of clinical trials on gastric cancer using everolimus and trametinib combination. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 22, 2020 Category: Cancer & Oncology Source Type: research

Evaluation of NUC-1031: a first-in-class ProTide in biliary tract cancer
ConclusionNUC1031 did not exhibit evidence of superior activity over gemcitabine, as a single-agent, or in combination with cisplatin, in either our in vivo or in vitro BTC models. Given that the largest Phase 3 study (ClinicalTrials.gov: NCT0314666) to date in BTC is underway (N = 828) comparing NUC1031/cisplatin to gemcitabine/cisplatin, our results suggest that a more conservative clinical evaluation path would be more appropriate. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 21, 2020 Category: Cancer & Oncology Source Type: research

Assessing the translational value of pre-clinical studies for clinical response rate in oncology: an exploratory investigation of 42 FDA-approved small-molecule targeted anticancer drugs
ConclusionRelationships were identified for ratios of efficacious clinical exposures to typical preclinical pharmacology data and ORR for KIST in this retrospective analysis. Although the obtained datasets are limited, the relationships demonstrate that a systemic exposure relative to established pre-clinical pharmacology experiments for an investigational KIST could be used as a reference to assess if desired efficacy could be achieved. This approach may assist selection of the recommended phase 2 dose (RP2D) of an investigational drug. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 18, 2020 Category: Cancer & Oncology Source Type: research

CD73 as a target to improve temozolomide chemotherapy effect in glioblastoma preclinical model
AbstractGlioblastoma is the most devastating primary brain tumor and effective therapies are not available. Treatment is based on surgery followed by radio and chemotherapy with temozolomide (TMZ), but TMZ increases patient survival only by 2  months. CD73, an enzyme responsible for adenosine production, emerges as a target for glioblastoma treatment. Indeed, adenosine causes tumor-promoting actions and CD73 inhibition increases sensitivity to TMZ in vitro. Here, a cationic nanoemulsion to nasal delivery of siRNA CD73 (NE-siRNA CD73) ai ming glioblastoma treatment was employed alone or in combination with TMZ. In vitr...
Source: Cancer Chemotherapy and Pharmacology - May 16, 2020 Category: Cancer & Oncology Source Type: research

The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats
ConclusionsOur study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 15, 2020 Category: Cancer & Oncology Source Type: research

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats
AbstractPurposeSorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain. Numerous studies have pointed out changes in the pharmacokinetic parameters of TKIs when co-administered with paracetamol. The aim of the study was to assess drug –drug interactions (DDIs) between sor...
Source: Cancer Chemotherapy and Pharmacology - May 11, 2020 Category: Cancer & Oncology Source Type: research

Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil
ConclusionThese results indicate that FTD persists longer in tumors than in bone marrow, which may cause a sustained antitumor effect with tolerable hematotoxicity. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 22, 2020 Category: Cancer & Oncology Source Type: research

A phase I study of the effect of repeated oral doses of pantoprazole on the pharmacokinetics of a single dose of fedratinib in healthy male subjects
ConclusionCoadministration with pantoprazole did not have clinically meaningful effects on fedratinib PK. No new or unexpected safety signals were observed with fedratinib. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 22, 2020 Category: Cancer & Oncology Source Type: research

Intravenous 5-fluoro-2 ′-deoxycytidine administered with tetrahydrouridine increases the proportion of p16-expressing circulating tumor cells in patients with advanced solid tumors
ConclusionFurther study of FdCyd  + THU is potentially warranted in urothelial carcinoma but not NSCLC or breast or H&N cancer. Increase in the proportion of p16-expressing cytokeratin-positive CTCs is a pharmacodynamic marker of FdCyd target engagement. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 20, 2020 Category: Cancer & Oncology Source Type: research

The influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer patients received capecitabine-based adjuvant chemotherapy: a long-term follow-up, real-world retrospective study
This study investigated the influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer (CRC) patients who received capecitabine-based adjuvant chemotherapy in real world.MethodsA total of 315 CRC patients underwent R0 surgical resection and received capecitabine-based adjuvant chemotherapy were included. Clinical characteristics were collected from the hospital record system, prognosis was obtained by telephone follow-up. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of CRC patients were performed for the genotyping of polymorphism and mRNA expression of PD-L1, respecti...
Source: Cancer Chemotherapy and Pharmacology - April 20, 2020 Category: Cancer & Oncology Source Type: research

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib
ConclusionPexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 18, 2020 Category: Cancer & Oncology Source Type: research

Clinical pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation
ConclusionsIvosidenib 500-mg QD has favorable pharmacokinetic and pharmacodynamic profiles in patients with advanced hematologic malignancies with an IDH1 mutation.Clinical trial registrationClinicalTrials.gov NCT02074839. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 15, 2020 Category: Cancer & Oncology Source Type: research

Rapid decrease in serum VEGF-A levels may be a worse prognostic biomarker for patients with platinum-resistant recurrent ovarian cancer treated with bevacizumab and gemcitabine
AbstractPurposeThe aim of this study was to investigate the association between changes in the levels of vascular endothelial growth factors (VEGFs) after treatment with bevacizumab and gemcitabine (Bev-Gem) and the clinical outcome.MethodsPlatinum-resistant ovarian cancer patients treated with Bev-Gem therapy at our hospital between 2014 and 2018 were identified. Serum VEGF levels at the first and second treatment cycle were measured by ELISA. All patients were categorized into two groups —patients with >  50% decrease in serum VEGF-A levels (Group A) and patients with 
Source: Cancer Chemotherapy and Pharmacology - April 11, 2020 Category: Cancer & Oncology Source Type: research

Inhibition of cyclin-dependent kinases by AT7519 enhances nasopharyngeal carcinoma cell response to chemotherapy
ConclusionsOur work is the first to report anti-NPC activities of AT7519. Our preclinical evidence suggests that AT7519 is a useful addition to overcome NPC chemo-resistance. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 11, 2020 Category: Cancer & Oncology Source Type: research

Expression of Concern: shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 10, 2020 Category: Cancer & Oncology Source Type: research

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal, non-small cell lung, and pancreatic cancer
ConclusionLapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 9, 2020 Category: Cancer & Oncology Source Type: research

Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study
ConclusionTreatment with high-dose, once weekly sorafenib administration resulted in dose-limiting toxicity precluding dose escalation above the exposure cohort of 125 –150 mg/L/h. Drug monitoring was a successful strategy to pursue a target exposure. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 9, 2020 Category: Cancer & Oncology Source Type: research

A phase I study investigation of metabolism, and disposition of [ 14 C]-anlotinib after an oral administration in patients with advanced refractory solid tumors
ConclusionsAnlotinib had a good pharmacokinetic profile with rapid absorption, long half-life, and extensive hepatic metabolism. The adverse events and efficacy were as expected. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 7, 2020 Category: Cancer & Oncology Source Type: research

Effects of repeated oral doses of ketoconazole on a sequential ascending single oral dose of fedratinib in healthy subjects
ConclusionsThese results serve as the basis for fedratinib dose reduction when fedratinib is coadministered with strong CYP3A4 inhibitors. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 4, 2020 Category: Cancer & Oncology Source Type: research

Pharmacokinetics and pharmacogenetics of high-dose methotrexate in Chinese adult patients with non-Hodgkin lymphoma: a population analysis
ConclusionsThe MTX population pharmacokinetic model developed in this study might provide useful information for establishing personalized therapy involving MTX for the treatment of adult patients with NHL. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 3, 2020 Category: Cancer & Oncology Source Type: research

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer
ConclusionsOur study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 2, 2020 Category: Cancer & Oncology Source Type: research

Assessment of pharmacokinetic variations of capecitabine after multiple administration in rats: a physiologically based pharmacokinetic model
ConclusionThe decreased plasma concentration of capecitabine was caused by decreased metabolic enzyme activity. Efficacy can be improved by dose adjustment of capecitabine based on metabolic enzyme activities, using the PBPK model. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 2, 2020 Category: Cancer & Oncology Source Type: research

Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors
ConclusionNapabucasin was well-tolerated at doses up to 1440  mg/day in Japanese patients with advanced solid tumors; the PK profile was comparable to that reported previously. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 31, 2020 Category: Cancer & Oncology Source Type: research

Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer
ConclusionsThe immunoproteasome may be an effective therapeutic target in a subset of CR lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant SCLC and NSCLC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 30, 2020 Category: Cancer & Oncology Source Type: research

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma
ConclusionsPola PK was well characterized with no clinically meaningful DDIs with R/G-CHP. Findings are consistent with previous studies of pola  + R/G, and support pola + R/G-CHP use in previously untreated diffuse large B-cell lymphoma. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 28, 2020 Category: Cancer & Oncology Source Type: research

Correction to: Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer
In the original publication of the article the author has found few incorrect values in the Table 1. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 25, 2020 Category: Cancer & Oncology Source Type: research

SNPs in the COX-2/PGES/EP signaling pathway are associated with risk of severe capecitabine-induced hand-foot syndrome
ConclusionOur study showed that rs3810255 AG/GG genotypes and rs17131450 GG genotypes to be associated with high risk of capecitabine-induced HFS. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 19, 2020 Category: Cancer & Oncology Source Type: research

Efficacy and safety of immune checkpoint inhibitor monotherapy in pretreated elderly patients with non-small cell lung cancer
ConclusionsSubsequent-line ICI monotherapy in elderly patients, with previously treated NSCLC, was effective, safe and showed outcomes equivalent to those in non-elderly patients. Immunotherapy provides a survival benefit for elderly patients, who exhibit its efficacy and a favorable general condition. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 19, 2020 Category: Cancer & Oncology Source Type: research

Metabolism and pharmacokinetics characterization of metarrestin in multiple species
AbstractPurposeMetarrestin is a first-in-class pyrrolo-pyrimidine-derived small molecule targeting a marker of genome organization associated with metastasis and is currently in preclinical development as an anti-cancer agent. Here, we report the in vitro ADME characteristics and in vivo pharmacokinetic behavior of metarrestin.MethodsSolubility, permeability, and efflux ratio as well as in vitro metabolism of metarrestin in hepatocytes, liver microsomes and S9 fractions, recombinant cytochrome P450 (CYP) enzymes, and potential for CYP inhibition were evaluated. Single dose pharmacokinetic profiles after intravenous and ora...
Source: Cancer Chemotherapy and Pharmacology - March 17, 2020 Category: Cancer & Oncology Source Type: research

Single-center risk factor analysis for FOLFIRINOX associated febrile neutropenia in patients with pancreatic cancer
AbstractPurposeFOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC.MethodsWe collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea.ResultsMultivariate logistic regression analysis showed that female (OR, 3.24;P = 0.023), Eastern Cooperative ...
Source: Cancer Chemotherapy and Pharmacology - March 17, 2020 Category: Cancer & Oncology Source Type: research

A novel natural product, britanin, inhibits tumor growth of pancreatic cancer by suppressing nuclear factor- κB activation
In conclusion, br itanin has remarkable potential treatment effects against pancreatic cancer, and it could be developed as a new agent for pancreatic cancer chemotherapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 17, 2020 Category: Cancer & Oncology Source Type: research

Impact of tumour size measurement inter-operator variability on model-based drug effect evaluation
ConclusionsThe global evaluation of drug effect using modelling approaches might not be affected by inter-operator variability. However, the exploration of covariates for drug effect and the characterisation of an exposure –tumour shrinkage relationship seems limited by the high measurement variability that translates to a poor correlation of individual drug effect estimates. This might be addressed by the use of more precise computer-aided measurement methods. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 13, 2020 Category: Cancer & Oncology Source Type: research

Involvement of ER stress and reactive oxygen species generation in anti-cancer effect of CKD-516 for lung cancer
ConclusionThe findings suggest that CKD-516 exerts an anticancer effect in company with inducing ER stress and ROS production via microtubule disruption in lung cancer cells. CKD-516 may thus have therapeutic potential for lung cancer. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 11, 2020 Category: Cancer & Oncology Source Type: research

Time to CA19-9 nadir: a clue for defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma
ConclusionThe present study suggests that a 4 –6 months program might be a more suitable candidate for prospective assessment in comparison to shorter pre-defined period in patients who are candidates to surgery after primary chemotherapy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 10, 2020 Category: Cancer & Oncology Source Type: research

Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic –pharmacodynamic model in gastrointestinal cancer patients
ConclusionsBSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 9, 2020 Category: Cancer & Oncology Source Type: research

The role of deubiquitinating enzymes in cancer drug resistance
AbstractDrug resistance is a well-known phenomenon leading to a reduction in the effectiveness of pharmaceutical treatments. Resistance to chemotherapeutic agents can involve various intrinsic cellular processes including drug efflux, increased resistance to apoptosis, increased DNA damage repair capabilities in response to platinum salts or other DNA-damaging drugs, drug inactivation, drug target alteration, epithelial –mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic effects, or any combination of these mechanisms. Deubiquitinating enzymes (DUBs) reverse ubiquitination of target proteins, ...
Source: Cancer Chemotherapy and Pharmacology - March 7, 2020 Category: Cancer & Oncology Source Type: research

Docetaxel-loaded ultrasmall nanostructured lipid carriers for cancer therapy: in vitro and in vivo evaluation
AbstractLack of cancer-targeted delivery of chemotherapeutics is one of the major obstacles for successful cancer therapy. Nanostructured lipid carriers (NLC) have shown great promise in drug-delivery applications since they are highly scalable, biodegradable nanocarriers with high-drug-loading capacity. However, traditional method prepared NLC, the diameter of which range from 80 to 200  nm, is easily blocked and trapped in perivascular regions without further penetration. As a result, ultrasmall NLC with size under 100 nm or lower range are reported to be ideally tumor targeting carrier as it allows for superio...
Source: Cancer Chemotherapy and Pharmacology - March 7, 2020 Category: Cancer & Oncology Source Type: research

Aurora B kinase as a therapeutic target in acute lymphoblastic leukemia
ConclusionAurora B kinase was identified to be an active therapeutic target in a broad range of ALL cells. Combination therapy of barasertib and a microtubule-targeting drug is of clinical interest. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 6, 2020 Category: Cancer & Oncology Source Type: research

Evaluating primary intra-arterial chemotherapy versus intravenous plus intra-arterial chemotherapy for advanced intraocular retinoblastoma
ConclusionsWithin a 3-year follow-up period, IVC plus IAC produced no additional benefit over primary IAC for treating advanced intraocular retinoblastoma in terms of local tumor control and extending survival. Longer follow-up periods are required to assess long-term efficacy. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 2, 2020 Category: Cancer & Oncology Source Type: research

Relationship between vemurafenib plasma concentrations and survival outcomes in patients with advanced melanoma
ConclusionA plasma vemurafenibCss,min threshold of 50  mg/L is strongly associated with survival outcomes in patients with advanced melanoma. This new threshold needs to be validated prospectively in future studies. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 22, 2020 Category: Cancer & Oncology Source Type: research

A retrospective study of the correlation of in vitro chemosensitivity using ATP-TCA with patient clinical outcomes in acute myeloid leukemia
ConclusionsThe in vitro chemosensitivity as tested by ATP-TCA demonstrated a significant correlation with CR for chemotherapy and can be a useful tool to optimize personalized treatments for patients with AML. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 22, 2020 Category: Cancer & Oncology Source Type: research

Characterization of infections and hypogammaglobulinemia treated with the combination of pertuzumab and trastuzumab
ConclusionsOur data continue to support an increased risk of infections with Gram-positive cocci as a potentially serious adverse event in women treated with pertuzumab and trastuzumab. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 22, 2020 Category: Cancer & Oncology Source Type: research

Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin ® ) in patients with advanced non-squamous non-small cell lung cancer
ConclusionsThe population PK of PF-06439535 and bevacizumab-EU were well characterized by a two-compartment model. Covariate analysis did not reveal any appreciable differences between PK parameters for PF-06439535 and bevacizumab-EU in patients with NSCLC.Clinical trial registrationClinicalTrials.gov, NCT02364999. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 22, 2020 Category: Cancer & Oncology Source Type: research

Interstitial lung disease in advanced pancreatic ductal adenocarcinoma patients treated with gemcitabine and nab-paclitaxel combination therapy: a retrospective analysis
ConclusionILD was observed in 18.9% of PDAC patients treated with GnP therapy. With appropriate management, no prognostic influence was observed. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 22, 2020 Category: Cancer & Oncology Source Type: research

The impact of patient characteristics on enzalutamide pharmacokinetics and how this relates to treatment toxicity and efficacy in metastatic prostate cancer patients
ConclusionsWe observed that age and BMI did not influence systemic exposure in patients treated with enzalutamide. No relation of exposure with efficacy or fatigue was observed. Further research using enzalutamide at a lower dose is needed to understand the relation of enzalutamide exposure and fatigue. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 19, 2020 Category: Cancer & Oncology Source Type: research

Repair of DNA damage induced by the novel nucleoside analogue CNDAG through homologous recombination
ConclusionCNDAG-induced double-strand breaks are repaired mainly through homologous recombination. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 18, 2020 Category: Cancer & Oncology Source Type: research

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors
This study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer orBRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into...
Source: Cancer Chemotherapy and Pharmacology - February 15, 2020 Category: Cancer & Oncology Source Type: research