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Cancer Chemotherapy and Pharmacology

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https://www.readbyqxmd.com/read/30413868/real-world-use-of-sunitinib-in-japanese-patients-with-pancreatic-neuroendocrine-tumors-results-from-a-post-marketing-surveillance-study
#1
Kazuo Sato, Yasuharu Toyoshima, Shiho Moriyama, Yutaka Endo, Tetsuhide Ito, Emiko Ohki
BACKGROUND: Sunitinib is approved for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable, locally advanced or metastatic disease. Safety and efficacy data in Japanese patients are limited. We report outcomes from a post-marketing surveillance study of sunitinib treatment in Japanese patients. METHODS: Sunitinib 37.5 mg once daily was orally administered in Japanese patients aged ≥ 15 years with pNETs...
November 9, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30406840/exposure-response-relationship-of-olaratumab-for-survival-outcomes-and-safety-when-combined-with-doxorubicin-in-patients-with-soft-tissue-sarcoma
#2
Robin L Jones, Gary Mo, John R Baldwin, Patrick M Peterson, Robert L Ilaria, Ilaria Conti, Damien M Cronier, William D Tap
PURPOSE: Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab exposure-response relationship for progression-free survival (PFS), overall survival (OS), and safety. METHODS: PFS and OS data from the 133 patients enrolled in the phase 2 study were analysed using time-to-event modelling...
November 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30406839/steroidal-dimer-by001-inhibits-proliferation-and-migration-of-esophageal-cancer-cells-via-multiple-mechanisms
#3
Sai-Qi Wang, Kai-Rui Zhou, Xiao-Li Shi, Hui-Fang Lv, Liang-Yu Bie, Wei-Jie Zhao, Xiao-Bing Chen
OBJECTIVE: To investigate the potential inhibitory effects of structurally novel steroidal dimer by001 in esophageal cancer in vitro. METHODS: The cytotoxicity of by001 on esophageal, gastric, neuroblastoma and prostate cancer cells was examined MTT assay and colony formation assay. By001 induced apoptosis and production of intracellular reactive oxygen species on esophageal cancer cells Ec109, TE-1 and human normal gastric epithelial cells GES-1 was detected by flow cytometry...
November 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30406838/oral-administration-of-irinotecan-in-patients-with-solid-tumors-an-open-label-phase-i-dose-escalating-study-evaluating-safety-tolerability-and-pharmacokinetics
#4
I Kümler, P Grundtvig Sørensen, J Palshof, E Høgdall, W Skovrider-Ruminski, S Theile, A Fullerton, P G Nielsen, B Vittrup Jensen, D L Nielsen
BACKGROUND: Oral drug formulations have several advantages compared to intravenous formulation. Apart from patient convenience and favorable pharmacoeconomics, they offer the possibility of frequent drug administration at home. In this study, we present a new oral irinotecan formulation designed as an enteric coated immediate release tablet which in pre-clinical studies has shown good exposure with low variability. METHODS: A phase I, dose escalating study to assess safety, tolerability, pharmacokinetics and efficacy of an oral irinotecan formulation and to establish the maximum tolerated dose (MTD)...
November 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30406285/a-dose-escalation-study-of-docetaxel-oxaliplatin-and-s-1-dos-as-a-first-line-therapy-for-patients-with-unresectable-metastatic-gastric-cancer
#5
Yasushi Sato, Tamotsu Sagawa, Hiroyuki Ohnuma, Masahiro Hirakawa, Yasuo Takahashi, Kyoko Hamaguchi, Koshi Fujikawa, Takayuki Nobuoka, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Ichiro Takemasa, Tetsuji Takayama
PURPOSE: The aim of this study was to determine the recommended dose (RD) for a docetaxel/oxaliplatin/S-1 (DOS) regimen in patients with unresectable gastric cancer and to preliminarily evaluate its efficacy. METHODS: Previously untreated patients with histologically proven unresectable metastatic gastric cancer were enrolled (n = 16). Docetaxel and oxaliplatin were administered intravenously on day 8 and S-1 was administered orally twice a day on days 1-14...
November 7, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30386887/nonclinical-pharmacokinetics-and-in-vitro-metabolism-of-h3b-6545-a-novel-selective-er%C3%AE-covalent-antagonist-serca
#6
Nathalie Rioux, Sherri Smith, Manav Korpal, Morgan O'Shea, Sudeep Prajapati, Guo Zhu Zheng, Markus Warmuth, Peter G Smith
PURPOSE: H3B-6545, a novel selective estrogen receptor (ER)α covalent antagonist (SERCA) which inactivates both wild-type and mutant ERα, is in clinical development for the treatment of metastatic breast cancer. Preclinical studies were conducted to characterize the pharmacokinetics and metabolism of H3B-6545 in rat and monkeys. METHODS: The clearance and metabolic profiles of H3B-6545 were studied using rat, monkey and human hepatocytes, and reaction phenotyping was done using recombinant human cytochrome P450 enzymes...
November 1, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30386886/safety-of-intraperitoneal-paclitaxel-combined-with-conventional-chemotherapy-for-colorectal-cancer-with-peritoneal-carcinomatosis-a-phase-i-trial
#7
Koji Murono, Hiroshi Nagata, Kazuhiro Ishimaru, Shigenobu Emoto, Manabu Kaneko, Masaya Hiyoshi, Kazuhito Sasaki, Kensuke Otani, Yasutaka Shuno, Takeshi Nishikawa, Toshiaki Tanaka, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Kei Muro, Soichiro Ishihara
PURPOSE: Peritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis...
November 1, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30377778/pertuzumab-trastuzumab-and-taxane-based-treatment-for-visceral-organ-metastatic-trastuzumab-na%C3%A3-ve-breast-cancer-real-life-practice-outcomes
#8
Ece Esin, B Oksuzoglu, A Bilici, I Cicin, O Kostek, M A Kaplan, S Aksoy, B Y Aktas, O Ozdemir, A Alacacioglu, D Cabuk, A T Sumbul, A Sakin, S Paydas, E Yetisir, O Er, T Korkmaz, N Yildirim, T Sakalar, H Demir, M Artac, M Karaagac, H Harputluoglu, E Bilen, E Erdur, S Degirmencioglu, A Aliyev, T Cil, P Olgun, G Basaran, O Gumusay, A Demir, E Tanrikulu, P F Yumuk, Inanc Imamoglu, B Oyan, B Cetin, V Haksoyler, N Karadurmus, I Erturk, T Evrensel, H Yilmaz, I Beypinar, M Kocer, K N Pilanci, M Seker, Y Urun, N Yildirim, T Eren, U Demirci
PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4...
October 30, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30377777/dose-adjustment-of-irinotecan-based-on-ugt1a1-polymorphisms-in-patients-with-colorectal-cancer
#9
Hironori Fujii, Yunami Yamada, Daichi Watanabe, Nobuhisa Matsuhashi, Takao Takahashi, Kazuhiro Yoshida, Akio Suzuki
PURPOSE: Irinotecan is effective for metastatic colorectal cancer (mCRC). SN-38 is an active metabolite of irinotecan, which is formed by carboxylesterase and inactivated by UDP-glucuronyltransferase (UGT) 1A1. The UGT enzyme activity is reduced in patients with homozygous mutation in UGT1A1 genes (*6/*6, *28/*28 and *6/*28); thus dose reduction is required for prevention of severe adverse events associated with irinotecan. The present study was designed to investigate the relationship between UGT1A1 polymorphisms and the incidence of adverse events or the therapeutic effect in mCRC patients who received irinotecan...
October 30, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30374523/regorafenib-or-rechallenge-chemotherapy-which-is-more-effective-in-the-third-line-treatment-of-metastatic-colorectal-cancer
#10
Osman Köstek, Muhammet Bekir Hacıoğlu, Abdullah Sakin, Tarık Demir, Murat Sarı, Ozlem Ozkul, Murat Araz, Aysun Fatma Doğan, Nazım Can Demircan, Sernaz Uzunoğlu, İrfan Çiçin, Bülent Erdoğan
PURPOSE: To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting. MATERIALS AND METHODS: The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months...
October 29, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30368586/associations-among-regorafenib-concentrations-severe-adverse-reactions-and-abcg2-and-oatp1b1-polymorphisms
#11
Akimitsu Maeda, Kei Irie, Hitoshi Ando, Ayako Hasegawa, Hiroya Taniguchi, Shigenori Kadowaki, Kei Muro, Masahiro Tajika, Masahiro Aoki, Kazuhide Inaguma, Masaki Kajita, Akio Fujimura, Shoji Fukushima
PURPOSE: The ability of predicting severe adverse reactions caused by regorafenib is important. We evaluated regorafenib concentrations for adverse reaction risks and assessed the relevance of laboratory values and gene polymorphisms. METHODS: A total of 28 Japanese cancer patients who were treated with regorafenib were evaluated for the steady state of serum regorafenib concentrations and adverse reactions for 28 days. In addition, we determined the association of regorafenib concentrations with ABCG2 and OATP1B1 polymorphisms, which are regorafenib transporters...
October 27, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30368585/phase-i-study-of-bnc105p-carboplatin-and-gemcitabine-in-partially-platinum-sensitive-ovarian-cancer-patients-in-first-or-second-relapse-anzgog-1103
#12
Kristina Lindemann, Philip J Beale, Emma Rossi, Jeff C Goh, Michelle M Vaughan, Meaghan E Tenney, Julie K Martyn, Dirkje Sommeijer, Jose L Iglesias, Gabriel Kremmidiotis, Jeremy Simpson, Elizabeth Doolin, Tina C Lavranos, Annabell Leske, Anneso S Veillard, David Espinoza, Martin R Stockler, Danny Rischin
PURPOSE: The primary objective of this study was to determine the recommended dose of the vascular disrupting agent, BNC105P, in combination with gemcitabine and carboplatin in patients with ovarian cancer in first or second relapse with a minimum 4 month progression-free interval after last platinum. METHODS: Patients received carboplatin AUC4 on day 1 in combination with escalating doses of 800 or 1000 mg/m2 gemcitabine on days 1 and 8 and escalating doses of 12 or 16 mg/m2 BNC105P on days 2 and 9 every 21 days for a maximum for six cycles...
October 27, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30368584/effect-of-a-high-fat-meal-on-the-relative-bioavailability-of-h3b-6527-a-novel-fgfr4-inhibitor-in-healthy-volunteers
#13
Nathalie Rioux, Amy Kim, Darrell Nix, Todd Bowser, Markus Warmuth, Peter G Smith, Joanne Schindler
PURPOSE: This Phase I study estimated the effect of a high-fat meal on the pharmacokinetics (PK) of H3B-6527, a covalent inhibitor of the fibroblast growth factor receptor (FGFR) 4 in clinical development for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS: In this randomized, single center, single-dose, open-label, 2-period crossover study 12 healthy male volunteers, aged 18-55 years old, received a single 200-mg dose of H3B-6527 (capsule) following an overnight fast or a high-fat breakfast...
October 27, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30357450/plasma-and-brain-pharmacokinetics-of-letrozole-and-drug-interaction-studies-with-temozolomide-in-nod-scid-gamma-mice-and-sprague-dawley-rats
#14
Priyanka Arora, Courtney Huff Adams, Gary Gudelsky, Biplab DasGupta, Pankaj B Desai
PURPOSE: The aromatase inhibitor, letrozole, is being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs). To facilitate optimal dosing for such studies, we evaluated the plasma and brain pharmacokinetics (PK) of letrozole in NOD-scid gamma (NSG) mice, which are frequently employed for assessing efficacy against patient-derived tumor cells. Furthermore, we evaluated the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague-Dawley rats...
October 24, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30357449/effects-of-cyp2d6-10-polymorphism-on-tamoxifen-pharmacokinetics-in-patients-with-breast-cancer-in-asia-a-meta-analysis
#15
Yu Bai, Hai-Wei Wu, Yan-Hua Zhang
PURPOSE: Insufficient serum metabolite concentrations of tamoxifen can compromise treatment efficacy in patients with breast cancer. The purpose of this meta-analysis was to explore correlations between cytochrome P450 (CYP) 2D6*10 gene polymorphisms and serum concentrations of tamoxifen and its active metabolites in patients with breast cancer in Asia. METHODS: The study included a systematic literature search for cohort studies published before March 2018 in English databases (PubMed, Embase, Cochrane Library, and Web of Science) and Chinese databases (Chinese National Knowledge Infrastructure and Wan Fang database)...
October 24, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30353226/autophagy-and-its-potent-modulators-from-phytochemicals-in-cancer-treatment
#16
REVIEW
Chao-Yue Sun, Qian-Yu Zhang, Guang-Juan Zheng, Bing Feng
Autophagy is a ubiquitous catabolic process by which damaged or harmful intracellular components are delivered to the lysosomes for self-digestion and recycling. It is critical in cancer treatment. Therapy-induced autophagy predominantly acts as a pro-survival mechanism, but progressive autophagy can lead to non-apoptotic cell death, also known as autophagic cell death. Plants or herbs contain various natural compounds that are widely used in the treatment of many types of malignancies. Emerging evidence indicates that phytochemicals targeting the autophagic pathway are promising agents for cancer treatment...
October 23, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30350179/safety-of-trifluridine-tipiracil-in-an-open-label-expanded-access-program-in-elderly-and-younger-patients-with-metastatic-colorectal-cancer
#17
Robert J Mayer, Howard S Hochster, Steven J Cohen, Robert Winkler, Lukas Makris, Axel Grothey
PURPOSE: Trifluridine/tipiracil (FTD/TPI; TAS-102, Lonsurf®), a novel form of chemotherapy for metastatic colorectal cancer (mCRC), has shown clinical benefit in the global, phase III RECOURSE trial, regardless of patient age. Here, we report the safety and tolerability profile of FTD/TPI from an expanded-access program (EAP) in the US patients with mCRC whose disease has progressed on the standard therapies. METHODS: A total of 549 patients (≥ 18 years) with histologically confirmed mCRC following two or more regimens of standard therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1 participated in this open-label EAP...
October 22, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30350178/phase-i-trial-of-afatinib-and-3-weekly-trastuzumab-with-optimal-anti-diarrheal-management-in-patients-with-her2-positive-metastatic-cancer
#18
Nicolas Martin, Nicolas Isambert, Carlos Gomez-Roca, Rainer-Georg Goeldner, Sylvie Zanetta, Behbood Sadrolhefazi, Hélène de Mont-Serrat, Mario Campone, Jean-Pierre Delord
BACKGROUND: Trastuzumab is the mainstay of therapy for patients with HER2-positive breast and gastric cancer but resistance frequently occurs. Afatinib, an irreversible oral ErbB family blocker, shows clinical activity in trastuzumab-refractory HER2-positive metastatic breast cancer. MATERIALS AND METHODS: This phase I study used a modified 3 + 3 dose escalation design to determine the maximum tolerated dose (MTD) of oral once-daily afatinib in combination with 3-weekly intravenous trastuzumab (8 mg/kg week 1; 6 mg/kg 3-weekly thereafter) for patients with confirmed advanced or metastatic HER2-positive cancer...
October 22, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30327876/mononuclear-phagocyte-system-function-and-nanoparticle-pharmacology-in-obese-and-normal-weight-ovarian-and-endometrial-cancer-patients
#19
Brittney R Starling, Parag Kumar, Andrew T Lucas, David Barrow, Laura Farnan, Laura Hendrix, Hugh Giovinazzo, Gina Song, Paola Gehrig, Jeannette T Bensen, William C Zamboni
PURPOSE: Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. METHODS: Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured...
October 16, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/30324220/methotrexate-polyglutamate-levels-and-co-distributions-in-childhood-acute-lymphoblastic-leukemia-maintenance-therapy
#20
Jacob Nersting, Stine Nygaard Nielsen, Kathrine Grell, Maria Paerregaard, Jonas Abrahamsson, Bendik Lund, Olafur Gisli Jonsson, Kaie Pruunsild, Goda Vaitkeviciene, Jukka Kanerva, Kjeld Schmiegelow
PURPOSE: Methotrexate polyglutamates (MTXpg) facilitate incorporation of thioguanine nucleotides into DNA (DNA-TG, the primary cytotoxic thiopurine metabolite and outcome determinant in MTX/6-mercaptopurine treatment of childhood ALL). We hypothesized that mapping erythrocyte levels of MTXpg with 1-6 glutamates and their associations with DNA-TG formation would facilitate future guidelines for maintenance therapy dosing. METHODS AND RESULTS: Summed MTX with 1-6 glutamates resolved by LCMS [median (interquartile): 5...
October 15, 2018: Cancer Chemotherapy and Pharmacology
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