MiRNA-3662 reverses the gemcitabine resistance in pancreatic cancer through regulating the tumor metabolism
ConclusionsThis study sheds light on miRNA-3662 inhibits PDAC cell chemoresistance and aerobic glycolysis through a negative feedback loop with HIF-1 ɑ. Therefore, the co-delivery of miR-3662 and Gem could be served as a promising therapeutic regimen for PDAC patients. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 15, 2021 Category: Cancer & Oncology Source Type: research

Phase 1 study of alisertib (MLN8237) and weekly irinotecan in adults with advanced solid tumors
ConclusionIn contrast to prior results in a pediatric population, adult patients did not tolerate alisertib combined with irinotecan at clinically meaningful doses due to hematologic and gastrointestinal toxicities. The study was registered with ClinicalTrials.gov under study number NCT01923337 on Aug 15, 2013. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 15, 2021 Category: Cancer & Oncology Source Type: research

Autophagy inhibitor potentiates the antitumor efficacy of apatinib in uterine sarcoma by stimulating PI3K/Akt/mTOR pathway
ConclusionCombination of apatinib and autophagy inhibitor 3-MA significantly inhibited the growth and migration of uterine sarcoma cells and xenograft. Autophagy inhibition may increase the antitumor effect of apatinib via the PI3K/Akt/mTOR pathway. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 12, 2021 Category: Cancer & Oncology Source Type: research

Influence of genetic variants in asparaginase pathway on the susceptibility to asparaginase-related toxicity and patients' outcome in childhood acute lymphoblastic leukemia
ConclusionATF5 362TT and CT genotypes were associated with decreased risk to develop AAP and better disease outcome demonstrating a low risk for events and superior survival. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 7, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Changes in expression of lysosomal membrane proteins in leucocytes of cancer patients treated with tyrosine kinase inhibitors
In the Original publication of the article, the graphical abstract was not included. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 7, 2021 Category: Cancer & Oncology Source Type: research

An exploration of the impact of ethanol diluent on breath alcohol concentration in patients receiving paclitaxel chemotherapy
ConclusionAlthough definitive conclusions are limited by relatively small numbers, it seems unlikely that weekly paclitaxel infusions pose any significant risk to patients driving. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 4, 2021 Category: Cancer & Oncology Source Type: research

NCTR 25 fusion facilitates the formation of TRAIL polymers that selectively activate TRAIL receptors with higher potency and efficacy than TRAIL
ConclusionsNCTR25 fusion alone facilitates the formation of TRAIL polymers. Multivalent TRAIL polymers bind and activate DR4 and DR5 specifically and exclusively, triggering the signaling pathways with higher potency, and greater efficacy than TRAIL. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 4, 2021 Category: Cancer & Oncology Source Type: research

Exploratory analysis of target concentration of lenvatinib in the treatment of hepatocellular carcinoma
AbstractPurposeWe aimed to evaluate exposure –toxicity/efficacy relationship of lenvatinib by determining its target trough concentration for patients with hepatocellular carcinoma (HCC).MethodsIn this retrospective, observational study, 28 HCC patients who had been treated with lenvatinib were enrolled between August 2018 and April 2020. We evaluated the association between the trough lenvatinib concentration and occurrence of grade  ≥ 3 toxicities. Additionally, we estimated the association of the trough lenvatinib concentration with responder status (disease control; complete response, partial res...
Source: Cancer Chemotherapy and Pharmacology - April 29, 2021 Category: Cancer & Oncology Source Type: research

No association between relapse hazard and thiopurine methyltransferase geno- or phenotypes in non-high risk acute lymphoblastic leukemia: a NOPHO ALL2008 sub-study
AbstractPurpose6-mercaptopurine(6MP)/methotrexate maintenance therapy is essential to reduce relapse of childhood acute lymphoblastic leukemia (ALL). Common germline variants inTPMT cause low activity of thiopurine methyltransferase (TPMT) and higher 6MP metabolite (TGN) levels. Higher levels of TGNs incorporated into DNA (DNA-TG) and low TPMT activity have previously been associated with a lower relapse risk. We explored if TPMT geno- or phenotype was associated with DNA-TG levels and relapse rate in NOPHO ALL2008.MethodsTPMT genotype, repeated phenotyping, and DNA-TG measurements were collected in 918 children with non-h...
Source: Cancer Chemotherapy and Pharmacology - April 29, 2021 Category: Cancer & Oncology Source Type: research

Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen
ConclusionTo our knowledge, the present model is the first to allow a simultaneous description of irinotecan pharmacokinetics and of its four main metabolites. Moreover, a direct conversion of NPC into SN-38 had never been described before in a population pharmacokinetic model of irinotecan. The model will be useful to develop pharmacokinetic-pharmacodynamic models relating SN-38 concentrations to efficacy and digestive toxicities.Clinical trials registration numberClinicalTrials.gov identifier: NCT00559676. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 28, 2021 Category: Cancer & Oncology Source Type: research

Pharmacokinetics and safety of rucaparib in patients with advanced solid tumors and hepatic impairment
ConclusionPatients with moderate hepatic impairment showed mildly increased AUC0 –inf for rucaparib compared to patients with normal hepatic function. Although more patients with moderate hepatic impairment experienced TEAEs, only 2 TEAEs were considered treatment related. These results suggest no starting dose adjustment is necessary for patients with moderate hepatic impairment; however, close safety monitoring is warranted. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 28, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC- α and translocating PKC-δ
A correction to this paper has been published: https://doi.org/10.1007/s00280-021-04287-1 (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 28, 2021 Category: Cancer & Oncology Source Type: research

Time-dependent population PK models of single-agent atezolizumab in patients with cancer
ConclusionThe overall impact of covariates on atezolizumab CL did not warrant any change in atezolizumab dosing recommendations. The results support the hypothesis that variation in atezolizumab CL over time is associated with patients ’ disease status, as shown with other checkpoint inhibitors. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 27, 2021 Category: Cancer & Oncology Source Type: research

Tissue distribution of epirubicin after severe extravasation in humans
ConclusionSurgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 27, 2021 Category: Cancer & Oncology Source Type: research

Glaucocalyxin A induces apoptosis and autophagy in tongue squamous cell carcinoma cells by regulating ROS
ConclusionOur results consistently suggested that GLA can induce apoptosis and autophagy in TSCC cells by generating ROS. GLA may serve as a promising therapeutic drug for overcoming TSCC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 27, 2021 Category: Cancer & Oncology Source Type: research

Downregulation of SELENBP1 enhances oral squamous cell carcinoma chemoresistance through KEAP1 –NRF2 signaling
ConclusionSENENBP1 is identified as a novel protective biomarker for OSCC patients. Targeting at the miR-4786-3p –SELENBP1–KEAP1–NRF2 signaling axis may enhance the efficacy of chemotherapy for OSCC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 27, 2021 Category: Cancer & Oncology Source Type: research

Population pharmacokinetics and exposure –response of selumetinib and its N‐ desmethyl metabolite in pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas
ConclusionFindings support continuous selumetinib 25  mg/m2 bid in pediatric patients. Importantly, the updated dosing nomogram ensures that patients will receive a clinically active, yet tolerable, dose regardless of differences in BSA and allows dose reductions, if necessary. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 26, 2021 Category: Cancer & Oncology Source Type: research

Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever
ConclusionWe developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success.Graphic abstract (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 20, 2021 Category: Cancer & Oncology Source Type: research

Cardiovascular toxicity of breast cancer treatment: an update
AbstractNovel chemotherapeutic agents have marked a new era in oncology during the past decade, prolonging significantly the overall survival of breast cancer patients. Nevertheless, contemporary antineoplastic treatments can frequently cause adverse cardiovascular side effects. Common manifestations of chemotherapy-induced cardiotoxicity include cardiomyopathy, ischemia, conduction disturbances, hypertension and thromboembolic events, while the type of the treatment regimen administered crucially determines clinical outcome. The aim of this literature review is to analyze the incidence and the underlying mechanisms of car...
Source: Cancer Chemotherapy and Pharmacology - April 17, 2021 Category: Cancer & Oncology Source Type: research

Upregulation of TRIB2 by Wnt/ β-catenin activation in BRAF V600E papillary thyroid carcinoma cells confers resistance to BRAF inhibitor vemurafenib
ConclusionOur study showed that the upregulation of TRIB2 by the Wnt/ β-catenin activation confers resistance to vemurafenib in PTC withBRAFV600 mutation. These findings support the potential use of TRIB2 as a therapeutic target for resistant PTC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 16, 2021 Category: Cancer & Oncology Source Type: research

Sorafenib combined with dasatinib therapy inhibits cell viability, migration, and angiogenesis synergistically in hepatocellular carcinoma
ConclusionSrc/FAK phosphorylation and cancer stem cell activation inducing cell migration and angiogenesis may be the key factors of sorafenib resistance. Sorafenib and dasatinib combined treatment suppresses cell migration and angiogenesis by inhibiting the Src/FAK phosphorylation, cell-to-cell contact, cancer stem cell activation, and release of vascular endothelial growth factor. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 16, 2021 Category: Cancer & Oncology Source Type: research

Correction to: PDK4 promotes tumorigenesis and cisplatin resistance in lung adenocarcinoma via transcriptional regulation of EPAS1
A correction to this paper has been published: https://doi.org/10.1007/s00280-021-04275-5 (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 15, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Formulae recently proposed to estimate renal glomerular filtration rate improve the prediction of carboplatin clearance
A correction to this paper has been published: https://doi.org/10.1007/s00280-021-04268-4 (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 13, 2021 Category: Cancer & Oncology Source Type: research

Evaluation of clinical outcomes and efficacy of palonosetron and granisetron in combination with dexamethasone in Egyptian patients receiving highly emetogenic chemotherapy
This study aimed to evaluate the antiemetic efficacy of palonosetron (PALO) over granisetron (GRA) in combination with dexamethasone for multiple highly emetogenic chemotherapy drugs (H EC), especially in chemotherapy regimens in Egyptian breast cancer patients and cisplatin-based regimens in other diseases.Patients and methodsAn open-label randomized trial was carried out, including 115 patients receiving at least four cycles of highly emetogenic chemotherapy regimens. All patients received dexamethasone in combination with the 5-HT3 receptor antagonist. We recorded patients' clinical and biochemical characteristics and w...
Source: Cancer Chemotherapy and Pharmacology - April 9, 2021 Category: Cancer & Oncology Source Type: research

Pharmacokinetics, safety, activity, and biomarker analysis of palbociclib plus letrozole as first-line treatment for ER+/HER2 – advanced breast cancer in Chinese women
ConclusionsPharmacokinetic and pharmacodynamic effects of palbociclib were well characterized in Chinese patients with ABC. Despite higher exposure, pharmacokinetic parameters were similar to those of a previously studied non-Asian population. No palbociclib dose adjustment based on Chinese ethnicity is needed. Palbociclib-letrozole had a manageable safety profile.Clinical trial registrationNCT02499146 (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 9, 2021 Category: Cancer & Oncology Source Type: research

Phase I study of tamibarotene monotherapy in pediatric and young adult patients with recurrent/refractory solid tumors
ConclusionsThe recommended dose for phase II study of tamibarotene in pediatric and young adult patients with refractory solid tumors is 12  mg/m2/day for 21  days in a 28 day cycle. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 7, 2021 Category: Cancer & Oncology Source Type: research

Impact of adverse events of adjuvant and neoadjuvant chemotherapies on outcomes of patients with pancreatic ductal adenocarcinoma
AbstractPurposeRecently, the number of patients with pancreatic ductal adenocarcinoma (PDAC) who have received both neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) has been increasing. However, whether adverse events (AEs) during AC influence the prognosis of patients with resected PDAC who do or do not receive NAC remains uncertain.MethodsPatients with PDAC who underwent a pancreatectomy between 2011 and 2019 were divided into two groups: an upfront surgery (UFS) group (n = 72), and an NAC group (n = 77). Patients who received AC were then divided into two groups: an AE grade 0/1/...
Source: Cancer Chemotherapy and Pharmacology - April 7, 2021 Category: Cancer & Oncology Source Type: research

Use of cucurbitacins for lung cancer research and therapy
AbstractAs the main substance in some traditional Chinese medicines, cucurbitacins have been used to treat hepatitis for decades in China. Currently, the use of cucurbitacins against cancer and other diseases has achieved towering popularity among researchers worldwide, as detailed in this review with summarized tables. Numerous studies have reported the potential tumor-killing activities of cucurbitacins in multiple aspects of human malignancies. Continuous research on its anticancer activity mechanisms also brings a glimmer of light to the treatment of patients with lung cancer. In line with the promising roles of cucurb...
Source: Cancer Chemotherapy and Pharmacology - April 6, 2021 Category: Cancer & Oncology Source Type: research

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy –naïve patient: a case report
ConclusionLow doses of enzalutamide may be efficacious, while also reducing the risk of side effects. Furthermore, employing a lower dose would reduce healthcare costs and increase access to enzalutamide. Studies exploring the efficacy of lower enzalutamide doses are warranted. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 4, 2021 Category: Cancer & Oncology Source Type: research

Clinical pharmacology strategies in supporting drug development and approval of antibody –drug conjugates in oncology
AbstractAntibody –drug conjugates (ADCs) are important molecular entities in the treatment of cancer. These conjugates combine the target specificity of monoclonal antibodies with the potent anti-cancer activity of small-molecule therapeutics. The complex structure of ADCs poses unique challenges to characterize t he drug’s pharmacokinetics (PKs) and pharmacodynamics (PDs) since it requires a quantitative understanding of the PK and PD properties of multiple different molecular species (e.g., ADC conjugate, total antibody and unconjugated cytotoxic drug). As a result, clinical pharmacology strategy of an AD C i...
Source: Cancer Chemotherapy and Pharmacology - April 1, 2021 Category: Cancer & Oncology Source Type: research

Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases
AbstractPurposeSwitch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases.MethodsThe medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing ...
Source: Cancer Chemotherapy and Pharmacology - March 31, 2021 Category: Cancer & Oncology Source Type: research

Changes in expression of lysosomal membrane proteins in leucocytes of cancer patients treated with tyrosine kinase inhibitors
Conclusion: prolonged treatment of cancer patients with SUN and IM did not induce leucocyte lysosomal biogenesis but dramatically  affected expression of ATP6V1B2. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 30, 2021 Category: Cancer & Oncology Source Type: research

The pharmacokinetics of pamiparib in the presence of a strong CYP3A inhibitor (itraconazole) and strong CYP3A inducer (rifampin) in patients with solid tumors: an open-label, parallel-group phase 1 study
ConclusionsPamiparib plasma exposure was reduced 38 –43% with rifampin coadministration but was unaffected by itraconazole coadministration. Pamiparib dose modifications are not considered necessary when coadministered with CYP3A inhibitors. Clinical safety and efficacy data will be used with these results to recommend dose modifications when pamip arib is coadministered with CYP3A inducers. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 27, 2021 Category: Cancer & Oncology Source Type: research

Selinexor population pharmacokinetic and exposure –response analyses to support dose optimization in patients with diffuse large B-cell lymphoma
AbstractPurposeCharacterize the population PK and exposure –response (ER) relationships of selinexor in patients with diffuse large B-cell lymphoma (DLBCL) (efficacy endpoints) or other non-Hodgkin’s lymphoma (NHL) patients (safety endpoints) to determine the optimal dose in patients with DLBCL.MethodsThis work included patients from seven clinical studies, with 800 patients for PK, 175 patients for efficacy and 322 patients for safety analyses. Logistic regression models and Cox-regression models were used for binary and time-to-event endpoints, respectively. Model-based simulations were performed to justify d...
Source: Cancer Chemotherapy and Pharmacology - March 26, 2021 Category: Cancer & Oncology Source Type: research

Oral recombinant methioninase combined with paclitaxel arrests recalcitrant ovarian clear cell carcinoma growth in a patient-derived orthotopic xenograft (PDOX) nude-mouse model
AbstractPurposeAdvanced ovarian clear cell carcinoma (OCCC) is a recalcitrant disease, often resistant to the first-line platinum-based therapy. Using a novel patient-derived orthotopic xenograft (PDOX) nude-mouse model of OCCC, we tested whether oral-recombinant methioninase (o-rMETase) could enhance the efficacy of paclitaxel (PTX).MethodsThe OCCC PDOX model was established and passaged in nude mice. The OCCC PDOX models were randomized into 5 groups. G1: untreated control; G2: paclitaxel (PTX) (20  mg/kg, intraperitoneal (i.p.) injection, weekly); G3: o-rMETase (100 units, oral, daily); G4: PTX (20 mg/kg, i.p....
Source: Cancer Chemotherapy and Pharmacology - March 25, 2021 Category: Cancer & Oncology Source Type: research

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function
AbstractThe introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack...
Source: Cancer Chemotherapy and Pharmacology - March 25, 2021 Category: Cancer & Oncology Source Type: research

Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study
This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response).MethodsEligible patients (pts) suitable for Irinotecan-based therapy. At baseline: (i) PGs: blood analyzed by the Affymetrix-DMET ™-Plus-Array (1936 variants: 1931 single nucleotide polymorphisms [SNPs] and 5 copy number variants in 225 genes, including 47 phase I, 80 phase II enzymes, and membrane transporters) and Sanger sequencing (variants in HNF1A, Topo-1, XRCC1, PARP1, TDP, CDC45L, NKFB1, and MTHFR), (ii) HNI: pts give n IV 250 MBq-99mTc-IDA, data deri...
Source: Cancer Chemotherapy and Pharmacology - March 23, 2021 Category: Cancer & Oncology Source Type: research

Dynamics of leucocyte DNA thioguanine nucleotide levels during maintenance therapy of childhood acute lymphoblastic leukemia
AbstractPurposeMethotrexate (MTX)/6-Mercaptopurine (6MP)-based maintenance therapy is crucial to cure childhood acute lymphoblastic leukemia (ALL). Cytotoxicity is mediated by incorporation of thioguanine nucleotides (TGN) into DNA (DNA-TG) with higher levels in leucocytes being associated with reduced relapse risk. To further understand the dynamics of DNA-TG formation, we measured DNA-TG levels in leucocyte subsets during maintenance therapy and in the months following its discontinuation.MethodsDNA-TG levels were measured in leucocytes (DNA-TGTotal), polymorph nucleated granulocytes (neutrophils, eosinophils, basophils ...
Source: Cancer Chemotherapy and Pharmacology - March 23, 2021 Category: Cancer & Oncology Source Type: research

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)
ConclusionsThese results support the choice of niraparib 200  mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC.Trial registration no.NCT02924766 (ClinicalTrials.gov). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 22, 2021 Category: Cancer & Oncology Source Type: research

Pharmacokinetics of docetaxel and ritonavir after oral administration of ModraDoc006/r in patients with prostate cancer versus patients with other advanced solid tumours
ConclusionThe exposure to docetaxel and ritonavir was significantly lower in prostate cancer patients as compared to patients with other types of solid tumours, treated on ModraDoc006/r 30 –20/100–100. An increase of the ritonavir dose increased the docetaxel exposure in mCRPC patients. Therefore, a different RP2D of ModraDoc006/r is pursued in castrated prostate cancer patients as compared to patients with other types of solid tumours.Trial registrationStudy 1: ClinicalTrials.gov Identifier NCT01173913, date of registration August 2, 2010. Study 2: ClinicalTrials.gov Identifier NCT03066154, date of registratio...
Source: Cancer Chemotherapy and Pharmacology - March 20, 2021 Category: Cancer & Oncology Source Type: research

Anticancer potential of metformin: focusing on gastrointestinal cancers
AbstractGastrointestinal cancers are one of the most common types of cancer that have high annual mortality; therefore, identification and introduction of safe drugs in the control and prevention of these cancers are of particular importance. Metformin, a lipophilic biguanide, is the most commonly prescribed agent for type 2 diabetes management. In addition to its great effects on lowering the blood glucose concentrations, the anti-cancer properties of this drug have been reported in many types of cancers such as gastrointestinal cancers. Hence the effects of this agent as a safe drug on the reduction of gastrointestinal c...
Source: Cancer Chemotherapy and Pharmacology - March 20, 2021 Category: Cancer & Oncology Source Type: research

Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients
AbstractPurposeResistance to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in some patients with locally advanced breast cancer remains one of the main obstacles to first-line treatment. We investigated clinical and pathological responses to FAC neoadjuvant chemotherapy in Mexican women with breast cancer and their possible association with SNPs present in ABC transporters as predictors of chemoresistance.MaterialsA total of 102 patients undergoing FAC neoadjuvant chemotherapy were included in the study. SNP analysis was performed by RT-PCR from genomic DNA. Two SNPs were analyzed: A...
Source: Cancer Chemotherapy and Pharmacology - March 19, 2021 Category: Cancer & Oncology Source Type: research

Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition
ConclusionThe results indicated that foretinib might have the therapeutic potential against human GBM which deserve further investigation. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 10, 2021 Category: Cancer & Oncology Source Type: research

Comparison of a thymine challenge test and endogenous uracil –dihydrouracil levels for assessment of fluoropyrimidine toxicity risk
ConclusionsThe endogenous uracil-based parameters, adjusted to CrCL, were more predictive of increased risk of severe fluoropyrimidine toxicity thanDPYD genotyping. However, endogenous U measurement detected fewer cases of severe toxicity than the THY challenge test. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 9, 2021 Category: Cancer & Oncology Source Type: research

Detecting DPD deficiency: when perfect is the enemy of good
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 9, 2021 Category: Cancer & Oncology Source Type: research

A pharmacologically-based approach to high dose methotrexate administration to investigate nephrotoxicity and acute kidney injury biomarkers in children and adolescents with newly diagnosed osteosarcoma
ConclusionsReducing peak serum and urine MTX concentration by prolonging the infusion duration did not alter risk of acute kidney injury. GFRcysC was decreased at the end of therapy. Proteinuria and elevations in AKI biomarkers indicate that direct tubular damage contributes to HDMTX nephrotoxicity.Clinical TrialNCT01848457. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 7, 2021 Category: Cancer & Oncology Source Type: research

Pharmacokinetics of UGN-101, a mitomycin-containing reverse thermal gel instilled via retrograde catheter for the treatment of low-grade upper tract urothelial carcinoma
AbstractPurposeTo evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial.MethodsPharmacokinetic parameters (Cmax,Tmax, AUC(0 –6),λz,t½, and AUCinf) were evaluated in six participants (male or female,  ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma s...
Source: Cancer Chemotherapy and Pharmacology - March 7, 2021 Category: Cancer & Oncology Source Type: research

Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens
AbstractPurposeAsparaginases, key agents in treatment of acute lymphoblastic leukemia (ALL), are associated with venous thromboembolism (VTE). While risks of short-acting asparaginase-related VTE is well-known, we studied VTE incidence and risk factors in adult ALL patients treated with and without long-acting pegylated asparaginase (PegA).MethodsSingle-center, retrospective analysis of 89 ALL patients treated with (n = 61) or without (n = 28) PegA at Greenebaum Comprehensive Cancer Center. Reviewed patient and disease characteristics, treatment, and VTE incidence.ResultsVTE during treatment occ...
Source: Cancer Chemotherapy and Pharmacology - March 7, 2021 Category: Cancer & Oncology Source Type: research

Clinical significance of circulating tumor cells in the response to trastuzumab for HER2-negative metastatic gastric cancer
ConclusionThe present results indicate the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 28, 2021 Category: Cancer & Oncology Source Type: research

Associations among plasma concentrations of regorafenib and its metabolites, adverse events, and ABCG2 polymorphisms in patients with metastatic colorectal cancers
This study assessed the trough plasma concentrations (Ctrough) of regorafenib and its N-oxide (M2) and N-oxide/desmethyl (M5)  metabolites, and evaluated the associations among these levels, adverse events, and pharmacokinetic-related genetic polymorphisms in patients with metastatic colorectal cancer.MethodsTheCtrough levels of regorafenib and its metabolites were assessed in a single-center, prospective, observational study, 7  days after the initial treatment. The correlation between those values and adverse events was then examined. In addition, the genetic polymorphisms ofABCG2,SLCO1B1, andUGT1A9 were determ...
Source: Cancer Chemotherapy and Pharmacology - February 26, 2021 Category: Cancer & Oncology Source Type: research