8,486 results match your criteria Cancer chemotherapy and pharmacology[Journal]


A randomized, double-blind, parallel-group, single‑dose, pharmacokinetic bioequivalence study of INTP24 and bevacizumab in healthy adult men.

Cancer Chemother Pharmacol 2020 Jul 5. Epub 2020 Jul 5.

Intas Pharmaceuticals Ltd. (Biopharma Division), Plot No: 423/P/A, Sarkhej-Bavla Highway, Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India.

Purpose: To demonstrate pharmacokinetic (PK) equivalence and to compare safety of INTP24 (bevacizumab biosimilar) with that of US-bevacizumab and EU-bevacizumab in healthy male subjects.

Methods: In this randomized, parallel-group, double-blind study, male subjects were randomized (1:1:1) to receive a single 1 mg/kg intravenous infusion of either INTP24, US-bevacizumab, or EU-bevacizumab. The primary endpoint was area under serum concentration (AUC) from time zero to infinity (AUC). Read More

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http://dx.doi.org/10.1007/s00280-020-04111-2DOI Listing

Population pharmacokinetics-pharmacodynamics of sunitinib in pediatric patients with solid tumors.

Cancer Chemother Pharmacol 2020 Jul 4. Epub 2020 Jul 4.

Pfizer Global Product Development, 10646 Science Center Drive, CB10, La Jolla, CA, 92121, USA.

Purpose: The safety profile of sunitinib in children, including the impact of sunitinib exposure on safety endpoints, was assessed using population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) models.

Methods: Data were from two clinical studies in 59 children with solid tumors (age range 2-21 years, 28 male/31 female, body weight range 16.2-100 kg, body surface are [BSA] range 0. Read More

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http://dx.doi.org/10.1007/s00280-020-04106-zDOI Listing

Berberine chloride suppresses non-small cell lung cancer by deregulating Sin3A/TOP2B pathway in vitro and in vivo.

Cancer Chemother Pharmacol 2020 Jul 30;86(1):151-161. Epub 2020 Jun 30.

The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, China.

Purpose: Berberine chloride (BBC) is a well-known plant isoquinoline alkaloid derived from Berberis aristata. In this study, we aim to explore the effect of BBC on non-small cell lung cancer (NSCLC), and further expound the underlying mechanism of BBC induces NSCLC cell death in vitro and in vivo.

Methods: CCK-8 assay and colony formation assay were used to test the viability and colony formation ability of NSCLC cells. Read More

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http://dx.doi.org/10.1007/s00280-020-04050-yDOI Listing

Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study.

Cancer Chemother Pharmacol 2020 Jul 27;86(1):141-150. Epub 2020 Jun 27.

Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center (RUMC), P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.

Purpose: In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored.

Methods: Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Read More

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http://dx.doi.org/10.1007/s00280-020-04107-yDOI Listing

Sorafenib exposure and its correlation with response and safety in advanced hepatocellular carcinoma: results from an observational retrospective study.

Cancer Chemother Pharmacol 2020 Jul 25;86(1):129-139. Epub 2020 Jun 25.

Department of Pharmacy, Shiga University of Medical Science Hospital, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.

Purpose: Severe adverse events frequently occur in patients treated with sorafenib, whereas some patients have suboptimal response to sorafenib. We aimed to evaluate the association of sorafenib-induced toxicities and clinical outcomes with the pharmacokinetics of sorafenib in patients with hepatocellular carcinoma (HCC).

Methods: This was a retrospective, observational study in which 26 HCC patients who had been treated with sorafenib were enrolled between September 2010 and March 2015. Read More

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http://dx.doi.org/10.1007/s00280-020-04105-0DOI Listing

Reactive oxygen species in cancer: a paradox between pro- and anti-tumour activities.

Cancer Chemother Pharmacol 2020 Jul 22;86(1):1-13. Epub 2020 Jun 22.

Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, UNC, INICSA (CONICET-UNC), Pabellón Argentina, 2do Piso, Ciudad Universitaria, 5000, Córdoba, Argentina.

Cancer constitutes a group of heterogeneous diseases that share common features. They involve the existence of altered cellular pathways which result in uncontrolled cell proliferation. Deregulation of production and/or elimination of reactive oxygen species (ROS) appear to be a relevant issue in most of them. Read More

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http://dx.doi.org/10.1007/s00280-020-04103-2DOI Listing

A randomized phase II trial of cisplatin plus gemcitabine versus carboplatin plus gemcitabine in patients with completely resected non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT0703).

Cancer Chemother Pharmacol 2020 Jul 20;86(1):117-127. Epub 2020 Jun 20.

First Department of Medicine, Hokkaido University Hospital, Sapporo, Japan.

Purpose: This study evaluated the efficacy and safety of platinum plus gemcitabine (P/G) combinations as postoperative adjuvant chemotherapies for non-small cell lung cancer.

Methods: Patients with postoperative stage IB-IIIA non-small cell lung cancer were randomly assigned to receive either cisplatin plus gemcitabine (GP arm) or carboplatin plus gemcitabine (GC arm) every 3 weeks for four cycles. The primary endpoint was 2-year disease-free survival (DFS). Read More

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http://dx.doi.org/10.1007/s00280-020-04104-1DOI Listing

First evidence for the antitumor activity of nanoliposomal irinotecan with 5-fluorouracil and folinic acid in metastatic biliary tract cancer.

Cancer Chemother Pharmacol 2020 Jul 18;86(1):109-115. Epub 2020 Jun 18.

Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Background: Therapeutic options are limited for advanced, metastatic biliary tract cancer. The pivotal NAPOLI-1 trial demonstrated the superior clinical benefit of nanoliposomal irinotecan (Nal-IRI) in gemcitabine-pretreated patients with metastatic pancreatic ductal adenocarcinoma; however, the antitumor activity of Nal-IRI in biliary tract cancer is unknown. This is the first report describing the efficacy of Nal-IRI in biliary tract cancer. Read More

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http://dx.doi.org/10.1007/s00280-020-04094-0DOI Listing

Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2020 Jul 16;86(1):97-108. Epub 2020 Jun 16.

Clinical Pharmacology and Quantitative Pharmacology, R&D Clinical Pharmacology and Safety Sciences, AstraZeneca, 35 Gatehouse Drive, Waltham, MA, 02451, USA.

Purpose: To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors.

Methods: In this Phase I, open-label, randomized, two-period, two-sequence crossover study, the pharmacokinetics of a single 300 mg adavosertib dose were investigated in fed versus fasted states.

Results: Compared with the fasted state, a high-fat, high-calorie meal (fed state) decreased adavosertib maximum plasma concentration (C) by 16% and systemic exposure (area under the plasma concentration-time curve [AUC]) by 6%; AUC decreased by 7% and time to maximum plasma concentration was delayed by 1. Read More

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http://dx.doi.org/10.1007/s00280-020-04101-4DOI Listing
July 2020
2.769 Impact Factor

Assessment of effects of repeated oral doses of fedratinib on inhibition of cytochrome P450 activities in patients with solid tumors using a cocktail approach.

Cancer Chemother Pharmacol 2020 Jul 14;86(1):87-95. Epub 2020 Jun 14.

Bristol Myers Squibb, Summit, NJ, USA.

Purpose: Fedratinib, an oral selective kinase inhibitor with activity against both wild type and mutationally activated Janus kinase 2, has been approved for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis by the US Food and Drug Administration. In vitro studies indicated that fedratinib was an inhibitor of several cytochrome P450 (CYP) enzymes. The primary objective of this study was to evaluate the effects of repeated doses of fedratinib on the activity of CYP2D6, CYP2C19, and CYP3A4 in patients with solid tumors using a CYP probe cocktail. Read More

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http://dx.doi.org/10.1007/s00280-020-04102-3DOI Listing

C-reactive protein at 1 month after treatment of nivolumab as a predictive marker of efficacy in advanced renal cell carcinoma.

Cancer Chemother Pharmacol 2020 Jul 14;86(1):75-85. Epub 2020 Jun 14.

Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 2360004, Japan.

Purpose: Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Read More

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http://dx.doi.org/10.1007/s00280-020-04088-yDOI Listing

Comparison between single-agent and combination chemotherapy as second-line treatment for advanced non-small cell lung cancer: a multi-institutional retrospective analysis.

Cancer Chemother Pharmacol 2020 Jul 12;86(1):65-74. Epub 2020 Jun 12.

Basic Laboratory, Department of Oncology Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, Shandong, China.

Purpose: Doublet combination chemotherapy is commonly considered a second-line treatment for advanced non-small cell lung cancer (NSCLC) in China. This multi-institutional retrospective analysis evaluated and compared the efficacy between combination and mono-therapy after platinum-based first-line chemotherapy in Chinese patients with advanced NSCLC.

Methods: We retrospectively reviewed 335 patients who received second-line chemotherapy for advanced NSCLC. Read More

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http://dx.doi.org/10.1007/s00280-020-04091-3DOI Listing

Influences of preoperative metformin on immunological factors in early breast cancer.

Cancer Chemother Pharmacol 2020 Jul 12;86(1):55-63. Epub 2020 Jun 12.

Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 7008558, Japan.

Purpose: Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer. Read More

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http://dx.doi.org/10.1007/s00280-020-04092-2DOI Listing

New DPYD variants causing DPD deficiency in patients treated with fluoropyrimidine.

Cancer Chemother Pharmacol 2020 Jul 11;86(1):45-54. Epub 2020 Jun 11.

Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Doctor Esquerdo 46, 28007, Madrid, Spain.

Purpose: Several clinical guidelines recommend genetic screening of DPYD, including coverage of the variants c.1905 + 1G>A(DPYD*2A), c.1679T>G(DPYD*13), c. Read More

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http://dx.doi.org/10.1007/s00280-020-04093-1DOI Listing

Correction to: Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization.

Cancer Chemother Pharmacol 2020 Jul;86(1):163

Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

In the original publication of the article, the second author name has been misspelled. Read More

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http://dx.doi.org/10.1007/s00280-020-04090-4DOI Listing

YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects.

Cancer Chemother Pharmacol 2020 Jul 9;86(1):33-43. Epub 2020 Jun 9.

Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

Purpose: Polo-like kinase 4 (PLK4), a member of the polo-like kinase family, plays several important roles in mitotic regulation, including centrosome duplication, spindle formation, and cytokinesis. PLK4 overexpression is frequently detected in many human cancers, including ovarian cancer, and the inhibition of PLK4 activity results in cancer cell mitotic arrest and apoptosis. Therefore, PLK4 might be a valid therapeutic target for antitumor therapy. Read More

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http://dx.doi.org/10.1007/s00280-020-04098-wDOI Listing

Pharmacokinetics of tablet and liquid formulations of oral 6-mercaptopurine in children with acute lymphoblastic leukemia.

Cancer Chemother Pharmacol 2020 Jul 9;86(1):25-32. Epub 2020 Jun 9.

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.

Purpose: Mercaptopurine (6MP) is essential to cure childhood acute lymphoblastic leukemia (ALL). A liquid 6MP formulation was recently introduced to facilitate oral 6MP administration, especially to children. Its approval and bioequivalence with 6MP tablet were based on comparative pharmacokinetics in 60 healthy adults. Read More

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http://dx.doi.org/10.1007/s00280-020-04097-xDOI Listing

Validation of an online tool for early prediction of the failure-risk in gestational trophoblastic neoplasia patients treated with methotrexate.

Cancer Chemother Pharmacol 2020 Jul 4;86(1):15-24. Epub 2020 Jun 4.

Oncology Medical Department, CITOHL, Université Claude Bernard Lyon-1, Hospices Civils de Lyon, Lyon, France.

Purpose: In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics. Read More

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http://dx.doi.org/10.1007/s00280-020-04086-0DOI Listing

In vitro drug sensitivity (IDS) of patient-derived primary osteosarcoma cells as an early predictor of the clinical outcomes of osteosarcoma patients.

Cancer Chemother Pharmacol 2020 Jun 31;85(6):1165-1176. Epub 2020 May 31.

Musculoskeletal Science and Translational Research Center, Chiang Mai University, Chiang Mai, 50200, Thailand.

Purpose: Early prediction of clinical response to conventional chemotherapy is a significant factor in determining an overall treatment strategy for osteosarcoma.

Methods: Cells were extracted from treatment-naïve biopsies from 16 osteosarcoma patients who received a doxorubicin and cisplatin-based neoadjuvant chemotherapy regimen and their sensitivities to doxorubicin and cisplatin were measured as IC50 values. Associations of in vitro drug sensitivity (IDS) levels and clinical outcomes were examined. Read More

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http://dx.doi.org/10.1007/s00280-020-04081-5DOI Listing
June 2020
2.769 Impact Factor

NUC-1031 in biliary tract cancer: from bench to bedside and back?

Cancer Chemother Pharmacol 2020 Jun 31;85(6):1011-1014. Epub 2020 May 31.

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands.

In preclinical models of biliary tract cancer, NUC-1031 showed less potency than gemcitabine, no correlation with potential biomarkers and only moderate additive interaction in combination with cisplatin. These findings should prompt further careful pharmacological and translational studies to better define the purported therapeutic advantage of NUC-1031 over gemcitabine. That would be a more cautious approach than the phase III clinical trial which is planning to enrol 828 patients with biliary tract tumours to compare gemcitabine/cisplatin "conventional" treatment with or without NUC-1031. Read More

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http://dx.doi.org/10.1007/s00280-020-04080-6DOI Listing

Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug.

Cancer Chemother Pharmacol 2020 Jun 30;85(6):1153-1163. Epub 2020 May 30.

Instituto Nacional de Cancerologia, Mexico City, Mexico.

Purpose: Ivermectin is an antiparasitic drug that exhibits antitumor effects in preclinical studies, and as such is currently being repositioned for cancer treatment. However, divergences exist regarding its employed doses in preclinical works. Therefore, the aim of this study was to determine whether the antitumor effects of ivermectin are observable at clinically feasible drug concentrations. Read More

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http://dx.doi.org/10.1007/s00280-020-04041-zDOI Listing

Exposure-response analysis of endoxifen serum concentrations in early-breast cancer.

Cancer Chemother Pharmacol 2020 Jun 29;85(6):1141-1152. Epub 2020 May 29.

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.

Purpose: Tamoxifen is part of endocrine therapy in breast cancer treatment. Studies have indicated the use of endoxifen concentrations, tamoxifen active metabolite, to guide tamoxifen efficacy. Three endoxifen thresholds have been suggested (5. Read More

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http://dx.doi.org/10.1007/s00280-020-04089-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305085PMC

Protein expression profiling identifies differential modulation of homologous recombination by platinum-based antitumor agents.

Cancer Chemother Pharmacol 2020 Jun 28;85(6):1129-1140. Epub 2020 May 28.

Department of Experimental Therapeutics-1950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.

Purpose: Oxaliplatin and satraplatin demonstrate activity against cisplatin-resistant tumor cells. Although the two platinum analogs are structurally-related, oxaliplatin is more active. Therefore, studies focusing on protein expression profiling were undertaken to identify the molecular mechanism for the difference in antitumor activity. Read More

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http://dx.doi.org/10.1007/s00280-020-04085-1DOI Listing

Variants of carboxylesterase 1 have no impact on capecitabine pharmacokinetics and toxicity in capecitabine plus oxaliplatin treated-colorectal cancer patients.

Cancer Chemother Pharmacol 2020 Jun 26;85(6):1119-1128. Epub 2020 May 26.

Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

Purpose: Capecitabine is a prodrug that undergoes metabolism in three steps to form an active 5-fluorouracil (5-FU). The first step is primarily catalyzed by liver carboxylesterases (CES) 1. Here, we examined the effects of CES1 variants on pharmacokinetics and toxicity of capecitabine. Read More

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http://dx.doi.org/10.1007/s00280-020-04087-zDOI Listing

Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway.

Cancer Chemother Pharmacol 2020 Jun 24;85(6):1097-1108. Epub 2020 May 24.

The Second Clinical Medical College, Guangzhou Medical University, Guangzhou, 511436, Guangdong, People's Republic of China.

Purpose: Brusatol, a natural quassinoid that is isolated from a traditional Chinese herbal medicine known as Bruceae Fructus, possesses biological activity in various types of human cancers, but its effects in nasopharyngeal carcinoma (NPC) have not been reported. This study aimed to explore the effect and molecular mechanism of brusatol in NPC in vivo and in vitro.

Methods: The antiproliferative effect of brusatol was assessed by MTT and colony formation assays. Read More

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http://dx.doi.org/10.1007/s00280-020-04083-3DOI Listing

Pharmacokinetics and tolerability of fedratinib, an oral, selective Janus kinase 2 inhibitor, in subjects with renal or hepatic impairment.

Cancer Chemother Pharmacol 2020 Jun 24;85(6):1109-1117. Epub 2020 May 24.

Bristol Myers Squibb, 556 Morris Ave, Summit, NJ, 07901, USA.

Purpose: Fedratinib is an oral, selective Janus kinase 2 inhibitor that is approved in the United States for the treatment of patients with intermediate-2 or high-risk myelofibrosis. Pharmacokinetics and tolerability of fedratinib in subjects with renal impairment (RI) and hepatic impairment (HI) were evaluated in two separate studies.

Methods: In the renal study, male and female subjects with stable, chronic mild, moderate, and severe RI, as well as those with end-stage renal disease, were included. Read More

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http://dx.doi.org/10.1007/s00280-020-04084-2DOI Listing

A phase I dose-escalation study of the polyamine analog PG-11047 in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2020 Jun 23;85(6):1089-1096. Epub 2020 May 23.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, CRB 1, Room 551, Baltimore, MD, 21287, USA.

Purpose: Polyamines are essential for the sustained proliferation and biomass required by tumor cells. Bis-alkylated polyamine analogs are nonfunctional competitors of natural polyamines. Of these, PG-11047, a second-generation unsaturated analog of the polyamine spermine, has demonstrated anticancer activity in cell lines and animal models of multiple cancer types. Read More

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http://dx.doi.org/10.1007/s00280-020-04082-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337042PMC

MEK inhibition overcomes everolimus resistance in gastric cancer.

Cancer Chemother Pharmacol 2020 Jun 22;85(6):1079-1087. Epub 2020 May 22.

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 39 Jingzhou Street, Xiangyang, 441021, Hubei, People's Republic of China.

Background: Although substantial evidence has shown that the mammalian target of rapamycin (mTOR) pathway is an important therapeutic target in gastric cancer, the overall response rates in patients to mTOR inhibitor everolimus have been less than initially expected. We hypothesized that the limited efficacy of everolimus in gastric cancer is due to the activation of extracellular signal-regulated kinase (ERK).

Methods: ERK activation was investigated using western blot. Read More

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http://dx.doi.org/10.1007/s00280-020-04078-0DOI Listing

Evaluation of NUC-1031: a first-in-class ProTide in biliary tract cancer.

Cancer Chemother Pharmacol 2020 Jun 21;85(6):1063-1078. Epub 2020 May 21.

Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA.

Purpose: NUC1031 is a first-in-class ProTide, that is a gemcitabine pro-drug designed to overcome putative mechanisms of resistance, including decreased expression of hENT/hCNT transporters, absence of activating enzymes such as deoxycytidine kinase (dCK) and presence of degrading enzymes such as cytidine deaminase (CDA). We undertook comprehensive pre-clinical evaluation of NUC1031 in biliary tract cancer (BTC) models, given that gemcitabine/cisplatin is a standard first-line therapy in advanced BTC.

Methods: Here, we compared the in vitro activity of NUC1031 in comparison to gemcitabine, validate putative mechanism(s) of action, assessed potential biomarkers of sensitivity or resistance, and performed combination studies with cisplatin. Read More

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http://dx.doi.org/10.1007/s00280-020-04079-zDOI Listing
June 2020
2.769 Impact Factor

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.

Cancer Chemother Pharmacol 2020 Jun 18;85(6):1015-1027. Epub 2020 May 18.

Roche Innovation Center, New York City, New York, USA.

Purpose: To assess the translational value of anticancer preclinical models, we retrospectively investigated the relationships between preclinical data and clinical response rate for 42 small-molecule targeted anticancer drugs approved by the US FDA from 2001 to 2018.

Methods: For 42 FDA-approved drugs, relevant pre-clinical (IC, mouse PK/efficacy) and clinical (overall response rates [ORR], PK) data were extracted from the public domain. Relationships were investigated overall and separately by mechanism of action and solid vs liquid tumors. Read More

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http://dx.doi.org/10.1007/s00280-020-04076-2DOI Listing

CD73 as a target to improve temozolomide chemotherapy effect in glioblastoma preclinical model.

Cancer Chemother Pharmacol 2020 Jun 16;85(6):1177-1182. Epub 2020 May 16.

Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil.

Glioblastoma 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. Read More

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http://dx.doi.org/10.1007/s00280-020-04077-1DOI Listing

The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.

Cancer Chemother Pharmacol 2020 Jun 15;85(6):1049-1062. Epub 2020 May 15.

Department of Integrated Traditional Chinese and Western Medicine, Cancer Hospital of the University of Chinese Academy of Sciences/Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.

Background: Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Read More

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http://dx.doi.org/10.1007/s00280-020-04060-wDOI Listing

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats.

Cancer Chemother Pharmacol 2020 Jun 11;85(6):1039-1048. Epub 2020 May 11.

Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, 14 Św. Marii Magdaleny Str., 61-861, Poznań, Poland.

Purpose: Sorafenib 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. Read More

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http://dx.doi.org/10.1007/s00280-020-04075-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305075PMC

Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.

Cancer Chemother Pharmacol 2020 Jun 22;85(6):1029-1038. Epub 2020 Apr 22.

Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Purpose: Trifluridine (FTD) is the active component of the nucleoside chemotherapeutic drug trifluridine/tipiracil (FTD/TPI), which is approved worldwide for the treatment of patients with metastatic gastrointestinal cancer. FTD exerts cytotoxic effects via its incorporation into DNA, but FTD has not been detected in the tumor specimens of patients. The purpose of this study was to detect FTD in tumors resected from metastatic colorectal cancer (mCRC) patients who were administered FTD/TPI. Read More

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http://dx.doi.org/10.1007/s00280-020-04072-6DOI Listing

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.

Cancer Chemother Pharmacol 2020 May 22;85(5):995-1001. Epub 2020 Apr 22.

Bristol Myers Squibb, 556 Morris Ave, Summit, NJ, 07901, USA.

Purpose: Fedratinib, an oral, selective Janus kinase 2 inhibitor with activity against both wild-type and mutant Janus kinase 2, has pH-dependent solubility, with free solubility at pH 1. Concomitant administration of drugs that reduce gastric acid secretion, such as pantoprazole, may decrease the absorption of fedratinib and affect patient outcomes. The aim of this study was to evaluate the impact of 7-day repeated 40-mg doses of pantoprazole on the pharmacokinetic (PK) properties of a single 500-mg dose of fedratinib in healthy male subjects. Read More

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http://dx.doi.org/10.1007/s00280-020-04074-4DOI Listing

Intravenous 5-fluoro-2'-deoxycytidine administered with tetrahydrouridine increases the proportion of p16-expressing circulating tumor cells in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2020 May 20;85(5):979-993. Epub 2020 Apr 20.

Division of Cancer Treatment and Diagnosis, National Cancer Institute, 31 Center Drive, Bldg. 31 Room 3A-44, Bethesda, MD, 20892, USA.

Purpose: Following promising responses to the DNA methyltransferase (DNMT) inhibitor 5-fluoro-2'-deoxycytidine (FdCyd) combined with tetrahydrouridine (THU) in phase 1 testing, we initiated a non-randomized phase 2 study to assess response to this combination in patients with advanced solid tumor types for which tumor suppressor gene methylation is potentially prognostic. To obtain pharmacodynamic evidence for DNMT inhibition by FdCyd, we developed a novel method for detecting expression of tumor suppressor protein p16/INK4A in circulating tumor cells (CTCs).

Methods: Patients in histology-specific strata (breast, head and neck [H&N], or non-small cell lung cancers [NSCLC] or urothelial transitional cell carcinoma) were administered FdCyd (100 mg/m) and THU (350 mg/m) intravenously 5 days/week for 2 weeks, in 28-day cycles, and progression-free survival (PFS) rate and objective response rate (ORR) were evaluated. Read More

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http://dx.doi.org/10.1007/s00280-020-04073-5DOI Listing

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.

Cancer Chemother Pharmacol 2020 May 20;85(5):969-978. Epub 2020 Apr 20.

Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, China.

Purpose: 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.

Methods: A 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. Read More

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http://dx.doi.org/10.1007/s00280-020-04069-1DOI Listing

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib.

Cancer Chemother Pharmacol 2020 May 18;85(5):1003-1007. Epub 2020 Apr 18.

Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.

Purpose: Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment. This study aims to evaluate plasma pharmacokinetic parameters and estimate CNS penetrance of pexidartinib in a non-human primate (NHP) cerebrospinal fluid (CSF) reservoir model.

Methods: Five male rhesus macaques, each with a previously implanted subcutaneous CSF ventricular reservoir and central venous lines, were used. Read More

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http://dx.doi.org/10.1007/s00280-020-04071-7DOI Listing

Clinical pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation.

Cancer Chemother Pharmacol 2020 May 15;85(5):959-968. Epub 2020 Apr 15.

Agios Pharmaceuticals, Inc., Cambridge, MA, USA.

Purpose: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. Ivosidenib (AG-120) is a targeted, potent, oral inhibitor of the mutant IDH1 protein. We describe detailed pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation treated in a phase I study (ClinicalTrials. Read More

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http://dx.doi.org/10.1007/s00280-020-04064-6DOI Listing
May 2020
2.769 Impact Factor

Inhibition of cyclin-dependent kinases by AT7519 enhances nasopharyngeal carcinoma cell response to chemotherapy.

Cancer Chemother Pharmacol 2020 May 11;85(5):949-957. Epub 2020 Apr 11.

Medical Center, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No.19, Xinhua Road, Xiuying Distric, Haikou, 570311, Hainan Province, China.

Background: The poor outcomes in nasopharyngeal carcinoma (NPC) necessitate new treatments. AT7519 is a potent inhibitor of several cyclin-dependent kinases (CDKs) and is currently in the early phase of clinical development for cancer treatment. The potent anti-cancer activities of AT7519 have been reported in various cancers, but not in NPC. Read More

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http://dx.doi.org/10.1007/s00280-020-04068-2DOI Listing

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.

Cancer Chemother Pharmacol 2020 May 11;85(5):941-947. Epub 2020 Apr 11.

Departments of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Saitama, 359-8513, Japan.

Purpose: The 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.

Methods: Platinum-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. Read More

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http://dx.doi.org/10.1007/s00280-020-04070-8DOI Listing

Expression of Concern: shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells.

Cancer Chemother Pharmacol 2020 Jun;85(6):1183

Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, People's Republic of China.

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http://dx.doi.org/10.1007/s00280-020-04044-wDOI Listing

Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study.

Cancer Chemother Pharmacol 2020 May 9;85(5):931-940. Epub 2020 Apr 9.

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VUmc University Medical Center Amsterdam, Amsterdam, The Netherlands.

Background: (Pre)clinical evidence is accumulating that intermittent exposure to increased doses of protein kinase inhibitors may improve their treatment benefit. In this phase I trial, the safety of high-dose, pulsatile sorafenib was studied.

Patients And Methods: High-dose sorafenib was administered once weekly in exposure escalation cohorts according to a 3 + 3 design. Read More

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http://dx.doi.org/10.1007/s00280-020-04065-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188706PMC

Phase I study of lapatinib plus trametinib in patients with KRAS-mutant colorectal, non-small cell lung, and pancreatic cancer.

Cancer Chemother Pharmacol 2020 May 9;85(5):917-930. Epub 2020 Apr 9.

Utrecht University, Utrecht, The Netherlands.

Purpose: KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Read More

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http://dx.doi.org/10.1007/s00280-020-04066-4DOI Listing

A phase I study investigation of metabolism, and disposition of [C]-anlotinib after an oral administration in patients with advanced refractory solid tumors.

Cancer Chemother Pharmacol 2020 May 7;85(5):907-915. Epub 2020 Apr 7.

Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China.

Purpose: Anlotinib is a novel oral multi-targeted receptor tyrosine kinase inhibitor, which selectively inhibits VEGFR2/3, FGFR1-4, PDGFR α/β, c-kit, and Ret. It shows antitumor effect in patients with advanced refractory solid tumors. The detailed absorption, metabolism, and excretion pathways of anlotinib have not yet been fully investigated. Read More

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http://dx.doi.org/10.1007/s00280-020-04062-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188728PMC
May 2020
2.769 Impact Factor

Effects of repeated oral doses of ketoconazole on a sequential ascending single oral dose of fedratinib in healthy subjects.

Cancer Chemother Pharmacol 2020 May 4;85(5):899-906. Epub 2020 Apr 4.

Bristol Myers Squibb, 556 Morris Ave, Summit, NJ, 07901, USA.

Purpose: Fedratinib is an orally administered Janus kinase 2-selective inhibitor that is indicated for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis in the United States. Fedratinib is metabolized by multiple cytochrome P450s (CYPs) in vitro, with the predominant contribution from CYP3A4. The primary objective of this study was to evaluate the effects of 14-day repeated 200 mg twice daily (BID) oral doses of a strong CYP3A4 inhibitor, ketoconazole, on a sequential ascending single oral dose of fedratinib in healthy male subjects. Read More

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http://dx.doi.org/10.1007/s00280-020-04067-3DOI Listing

Pharmacokinetics and pharmacogenetics of high-dose methotrexate in Chinese adult patients with non-Hodgkin lymphoma: a population analysis.

Cancer Chemother Pharmacol 2020 May 3;85(5):881-897. Epub 2020 Apr 3.

Department of Pharmacy, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuma Road 420, Fuzhou, 350014, China.

Purpose: High-dose methotrexate (HD-MTX) is widely used in the treatment of non-Hodgkin lymphoma (NHL), but the pharmacokinetic properties of HD-MTX in Chinese adult patients with NHL have not yet been established through an approach that integrates genetic covariates. The purposes of this study were to identify both physiological and pharmacogenomic covariates that can explain the inter- and intraindividual pharmacokinetic variability of MTX in Chinese adult patients with NHL and to explore a new sampling strategy for predicting delayed MTX elimination.

Methods: A total of 852 MTX concentrations from 91 adult patients with NHL were analyzed using the nonlinear mixed-effects modeling method. Read More

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http://dx.doi.org/10.1007/s00280-020-04058-4DOI Listing

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

Cancer Chemother Pharmacol 2020 May 2;85(5):863-868. Epub 2020 Apr 2.

The Ottawa Hospital Cancer Centre and University of Ottawa, Ottawa, ON, Canada.

Background: Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS).

Methods: All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. Read More

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http://dx.doi.org/10.1007/s00280-020-04063-7DOI Listing

Assessment of pharmacokinetic variations of capecitabine after multiple administration in rats: a physiologically based pharmacokinetic model.

Cancer Chemother Pharmacol 2020 May 2;85(5):869-880. Epub 2020 Apr 2.

Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.

Purpose: Capecitabine is a prodrug of 5-fluorouracil (5-FU) used for the treatment of colorectal cancer, with a two-week course of administration. However, the variance in plasma concentration and metabolic enzyme activities after multiple administration of capecitabine and its metabolites is unknown. The aim of this study was to identify the variance and predict the plasma concentration profile of capecitabine and its metabolites, using metabolic enzyme activities, to develop a more effective and safer medication. Read More

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http://dx.doi.org/10.1007/s00280-020-04057-5DOI Listing

Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2020 May 31;85(5):855-862. Epub 2020 Mar 31.

Department of Gastroenterology and Gastrointestinal Oncology Division, National Cancer Center Hospital East, Kashiwa, Japan.

Purpose: Napabucasin is a cancer stemness inhibitor that targets a number of oncogenic pathways, including signal transducer and activator of transcription 3 (STAT3). Phase 1/2 studies suggest tolerability and anti-tumor activity in various types of cancer; a Phase 3 study of napabucasin plus standard therapy in colorectal cancer is ongoing. This is a Phase 1 dose-escalation study in patients with advanced solid tumors, and the first study of napabucasin in Japanese patients. Read More

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http://dx.doi.org/10.1007/s00280-020-04059-3DOI Listing