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Cancer Chemotherapy and Pharmacology

Ian Joseph Cohen, Helen Toledano, Jerry Stein, Yehuda Kollender, Eyal Fenig, Osnat Konen, Zvi Bar-Sever, Josephine Issakov, Meora Feinmesser, Smadar Avigad, Shifra Ash
PURPOSE: We report the unexpected absence of early relapse (before 30 months) in 24 consecutive patients with isolated limb primary Ewing sarcoma treated with an intensified pilot protocol, SCMCIE94. METHODS: Clinical data for the study were collected retrospectively from the patient files. The protocol included 6 courses of chemotherapy, split radiation, and limb salvage surgery. This SCMCIE94 protocol had been used in almost all the patients described in an earlier report, in whom those with non-pelvic isolated tumors and low/absent CD56 expression in Ewing sarcoma tumor cells were all long-term survivors...
February 15, 2019: Cancer Chemotherapy and Pharmacology
Toshio Kawata, Mitsuo Higashimori, Yohji Itoh, Helen Tomkinson, Martin G Johnson, Weifeng Tang, Fredrik Nyberg, Haiyi Jiang, Yusuke Tanigawara
PURPOSE: A prospective, multicenter, large-scale cohort with a nested case-control study (NCT00252759) was conducted to identify and quantify risk factors for interstitial lung disease (ILD) in Japanese patients with non-small-cell lung cancer who received gefitinib. This study reports the association between gefitinib exposure and the occurrence of ILD. METHODS: A total of 1891 gefitinib plasma concentrations from 336 patients were measured after first dose, at steady state, and at time of ILD occurrence...
February 14, 2019: Cancer Chemotherapy and Pharmacology
Alexander MacDonald, Graeme Scarfe, Dominic Magirr, Tinnu Sarvotham, Julie Charlton, Wolfram Brugger, Emma Dean
PURPOSE: Vistusertib is an orally bioavailable dual target of rapamycin complex (TORC) 1/2 kinase inhibitor currently under clinical investigation in various solid tumour and haematological malignancy settings. The pharmacokinetic, metabolic and excretion profiles of 14 Carbon-isotope (14 C)-labelled vistusertib were characterised in this open-label phase I patient study. METHODS: Four patients with advanced solid malignancies received a single oral solution dose of 14 C-labelled vistusertib...
February 13, 2019: Cancer Chemotherapy and Pharmacology
Xujiao Chen, Zhihui Chang, Zhaoyu Liu
PURPOSE: To explore the clinical significance of plasma D-dimer increase for transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC). METHODS: The clinical data of 80 PLC patients who underwent TACE in our hospital from January 2015 to January 2017 were collected, including the plasma D-dimer level 1 week before TACE (D0), D-dimer level 1 month after TACE (D1) and D-dimer level when the disease begins to progress (D2). 1 Month after TACE, these patients were divided into two groups according to the mRecist criteria: disease-controlled group (CR + PR + SD) and disease-progressing group (PD)...
February 13, 2019: Cancer Chemotherapy and Pharmacology
Lydia Sanchez, Astrid Bacle, Thierry Lamy, Pascal Le Corre
PURPOSE: Studies have documented potential drug-drug interactions (pDDIs) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents, and supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay...
February 13, 2019: Cancer Chemotherapy and Pharmacology
Chandra Prakash, Bin Fan, Syed Altaf, Sam Agresta, Hua Liu, Hua Yang
PURPOSE: Pharmacokinetics, absorption, metabolism, and excretion of ivosidenib, a mutant isocitrate dehydrogenase-1 inhibitor, were determined in healthy male subjects. METHODS: In this open-label phase I study, a single dose of [14 C]ivosidenib (500 mg, 200 µCi/subject) was orally administered to eight subjects (CYP2D6 extensive, intermediate, or poor metabolizers) under fasted conditions. Blood, plasma, urine, and fecal samples were assayed for radioactivity and profiled for metabolites...
February 13, 2019: Cancer Chemotherapy and Pharmacology
Kentaro Miyake, Tasuku Kiyuna, Kei Kawaguchi, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Yunfeng Li, Scott D Nelson, Takashi Murakami, Yukihiko Hiroshima, Ryusei Matsuyama, Michael Bouvet, Sant P Chawla, Shree Ram Singh, Itaru Endo, Robert M Hoffman
PURPOSE: Ewing's sarcoma (ES) is a rare and recalcitrant disease which is in need of a development of a novel effective therapy. The aim of this study was to investigate the efficacy of regorafenib on an ES tumor in a patient-derived orthotopic xenograft (PDOX) model. METHODS: The ES PDOX models were established orthotopically in the right chest wall of nude mice to match the site of the tumor in the donor patient. The ES PDOX models were randomized into three groups (G) when the tumor volume reached 75 mm3 : G1: untreated control; G2: doxorubicin (DOX) (i...
February 13, 2019: Cancer Chemotherapy and Pharmacology
Ou Yamaguchi, Kyoichi Kaira, Atsuto Mouri, Ayako Shiono, Kosuke Hashimoto, Yu Miura, Fuyumi Nishihara, Yoshitake Murayama, Kunihiko Kobayashi, Hiroshi Kagamu
BACKGROUND: Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure. METHODS: From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study...
February 13, 2019: Cancer Chemotherapy and Pharmacology
E Baudry, S Huguet, A L Couderc, P Chaibi, F Bret, C Verny, S Weill, O Madar, S Urien, Keyvan Rezai
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in elderly patients, and R-CHOP chemotherapy is the standard treatment protocol for DLBCL. Elderly patients (often defined as 75 years of age) are treated with anticancer drugs with precaution; however, the pharmacokinetics and pharmacodynamics (PK and PD) of these agents have not been thoroughly investigated in this population. In this study, we investigated the PK of cyclophosphamide (CP) and doxorubicin (DOXO) in elderly patients in order to verify if there is an influence of age on the PK of these anticancer drugs...
January 28, 2019: Cancer Chemotherapy and Pharmacology
Al-Motassem Yousef, Rand Farhad, Daniah Alshamaseen, Abrar Alsheikh, Mohammed Zawiah, Taha Kadi
BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the major malignancies affecting children in Jordan. Methotrexate (MTX) is the cornerstone of chemotherapy for ALL, and works by targeting enzymes involved in the folate pathway. We hypothesize that genetic polymorphisms of the folate pathway are associated with MTX toxicity in children with ALL. METHODS: A total of 64 children with ALL were included in this study; 31 (48.4%) boys and 33 (51.6%) girls aged 2-16 years...
January 25, 2019: Cancer Chemotherapy and Pharmacology
Alexander Hoemme, Holger Barth, Manuel Haschke, Stephan Krähenbühl, Florian Strasser, Claudia Lehner, Alexander von Kameke, Thomas Wälti, Beat Thürlimann, Martin Früh, Christoph Driessen, Markus Joerger
The risk of potential drug-drug interactions (PDI) is poorly studied in oncology. We included 105 patients with advanced non-small-cell lung cancer (NSCLC), 100 patients with advanced breast cancer (BC) and 100 patients of the palliative care unit (PCU) receiving systemic palliative treatment between 2010 and 2015. All patients suffered from advanced incurable cancer and received basic palliative care. PDI were assessed using the hospINDEX of all drugs approved in Switzerland in combination with a specific drug interaction software...
January 25, 2019: Cancer Chemotherapy and Pharmacology
M Campone, T Bachelot, F Penault-Llorca, A Pallis, V Agrapart, M J Pierrat, C Poirot, F Dubois, L Xuereb, C J Bossard, N Guigal-Stephan, B Lockhart, F Andre
PURPOSE: The primary objective of this multicentric dose allocation and dose expansion study was to determine the MTD and the DLTs of the lucitanib (a tyrosine kinase inhibitor of the FGFR/VEGFR/PDFGR pathways)/fulvestrant combination. METHODS: Postmenopausal women with ER+/HER2- mBC, who have relapsed during or after treatment with fulvestrant, were eligible. The study had a dose allocation part to assess the tolerability of the combination followed by a dose expansion part...
January 25, 2019: Cancer Chemotherapy and Pharmacology
Lin Guo, Hao Peng, Hua-Lin Cai, Dan Tang, Hao Hu, Feng Wang, Jia Liu, Kai-Lin Que, Chen Han, Ying Zhang, Miao Yan, Jin-An Ma
PURPOSE: To compare efficacy and safety of postponing administration of aprepitant and routine triple-antiemetic treatment for chemotherapy-induced nausea and vomiting in patients who received docetaxel and cisplatin multi-day chemotherapy treatment, and to evaluate the effect of aprepitant on docetaxel pharmacokinetics in the Chinese population. METHODS: A total of 24 cancer patients (including 5 females and 19 males, 22-74 years old) received two cycles of high-emetic DP (docetaxel 75 mg/m2  on day 1 + cisplatin 25 mg/m2 on days 1-3) regimen...
January 24, 2019: Cancer Chemotherapy and Pharmacology
Osman Köstek, Erdem Yılmaz, Muhammet Bekir Hacıoğlu, Nazım Can Demircan, Ali Gökyer, Sernaz Uzunoğlu, Nermin Tunçbilek, İrfan Çiçin, Bülent Erdoğan
PURPOSE: To evaluate whether sunitinib and pazopanib treatments are associated with change in skeletal muscle area (SMA) and total lean body mass (LBM) as well as to compare their efficacies and safety profiles in patients with metastatic renal cell cancer (mRCC). METHODS: Thirty-six patients treated with a tyrosine kinase inhibitor were included. Eighteen of them received sunitinib and the rest/remaining received pazopanib in the first line of mRCC treatment. Baseline and follow-up computed tomography studies of the patients were performed to measure cross-sectional areas (cm2 ) of muscle tissues...
January 24, 2019: Cancer Chemotherapy and Pharmacology
Kathleen Moore, John K Chan, Angeles Alvarez Secord, Manish R Patel, Timothy Callahan, Wei Guo, Zhi-Yi Zhang
PURPOSE: Anticancer drugs may cause cardiovascular toxicities, including QT interval prolongation. Niraparib, a potent and selective once-daily oral poly (ADP-ribose) polymerase inhibitor, is approved as a maintenance therapy in platinum-sensitive recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC). Here, we present the effects of niraparib on cardiac repolarization, and the correlation between changes in baseline QT interval corrected by Fridericia's formula (ΔQTcF) and niraparib plasma concentrations...
January 24, 2019: Cancer Chemotherapy and Pharmacology
Mayu Osawa, Mayumi Hasegawa, Akintunde Bello, Amit Roy, Matthew W Hruska
PURPOSE: Nivolumab monotherapy provided clinically meaningful antitumor activity in Asian and non-Asian patients with chemotherapy-refractory gastric cancer (GC) or gastro-esophageal junction cancer (GEJC) in the ATTRACTION-2 and CheckMate 032 studies, respectively. This analysis assessed the population pharmacokinetics (PopPK) of nivolumab, the impact of covariates on pharmacokinetics (PK), and the PK of nivolumab flat dosing in GC/GEJC using samples from these studies. METHODS: PopPK analyses were conducted using data from 1302 patients with solid tumors, including 387 patients with GC/GEJC who had received nivolumab 3 mg/kg once every 2 weeks (Q2W)...
January 21, 2019: Cancer Chemotherapy and Pharmacology
Hannah Yejin Kim, Janna K Duong, Maria Gonzalez, Georgina V Long, Alexander M Menzies, Helen Rizos, Su Yin Lim, Jenny Lee, Alan V Boddy
PURPOSE: The combination of a BRAF inhibitor dabrafenib and a MEK inhibitor trametinib (CombiDT) has improved outcomes compared with chemotherapy or BRAF inhibitor monotherapy in advanced BRAF V600E/K melanoma. However, CombiDT causes a high incidence of pyrexia and treatment interruptions. Pharmacokinetic analysis may provide an explanation for the pyrexia. METHODS: 34 patients with Stage 3 BRAF V600 melanoma were treated with CombiDT on a clinical trial between August 2014 and June 2017...
January 19, 2019: Cancer Chemotherapy and Pharmacology
Maria Carolina Ruiz, Agustina Resasco, Ana Laura Di Virgilio, Miguel Ayala, Isabel Cavaco, Silvia Cabrera, Jose Aleman, Ignacio Esteban León
Platinum-based drugs, mainly cisplatin, are used for the treatment of several solid tumors such as OS. However, cisplatin treatment often results in the development of chemoresistance, leading therapeutic failure. We have previously reported that platinum complexes containing 8-hydroxyquinoline ligands have good antitumor activity against different cancer cell lines and with a different and better cytotoxic profile than cisplatin. Here, the anticancer properties of two different quinoline-platinum complexes [Pt(Cl)2 (quinoline)(dmso)] (1) [PtCl(8-O-quinoline)(dmso)] (2) on in vitro (2D and 3D) and in vivo models (xenograft tumor of human osteosarcoma in mice) are presented...
January 19, 2019: Cancer Chemotherapy and Pharmacology
Junya Sato, Hiroshi Ishikawa, Rei Tanaka, Michihiro Sino
PURPOSE: Hypomagnesemia is a common side effect of panitumumab. The effect of magnesium-containing supplement as a laxative and concomitant antacid (proton pump inhibitor and histamine H2 antagonist) administration on panitumumab-induced hypomagnesemia was retrospectively investigated. METHODS: Patients with advanced or recurrent colorectal cancer who received panitumumab were included in this study. Serum magnesium levels were extracted from the electronic medical records of 1753 administrations in 221 patients who received panitumumab...
January 19, 2019: Cancer Chemotherapy and Pharmacology
Yoriko Yamashita-Kashima, Yasushi Yoshimura, Takaaki Fujimura, Sei Shu, Mieko Yanagisawa, Keigo Yorozu, Koh Furugaki, Ryota Higuchi, Junichi Shoda, Naoki Harada
PURPOSE: Trastuzumab emtansine (T-DM1) provides clinical benefit in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2). However, its efficacy against biliary tract cancers (BTC) has not been evaluated. In this study, the effectiveness of T-DM1 in various BTC cell lines and xenograft models with different levels of HER2 expression was investigated. METHODS: HER2 expression status in xenografts and patient tissue microarrays was assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)...
January 18, 2019: Cancer Chemotherapy and Pharmacology
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