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Cancer Chemotherapy and Pharmacology

Masahiro Zenitani, Takashi Nojiri, Toru Kimura, Hiroshi Hosoda, Koichi Miura, Jun Hino, Kengo Nakahata, Shuichiro Uehara, Mikiya Miyazato, Takaharu Oue, Hiroomi Okuyama, Kenji Kangawa
PURPOSE: Cisplatin is an effective chemotherapeutic agent used to treat a variety of malignant tumors. The major toxicity associated with cisplatin treatment is granulocytopenia. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, protects against toxicity in many organs, including the heart, blood vessels, lung, and kidney. The objective of this study was to investigate the myeloprotective effects of CNP in a mouse model of cisplatin-induced granulocytopenia...
January 18, 2017: Cancer Chemotherapy and Pharmacology
Jeffrey R Infante, Amita Patnaik, Claire F Verschraegen, Anthony J Olszanski, Montaser Shaheen, Howard A Burris, Anthony W Tolcher, Kyriakos P Papadopoulos, Muralidhar Beeram, Scott M Hynes, Jennifer Leohr, Aimee Bence Lin, Lily Q Li, Anna McGlothlin, Daphne L Farrington, Eric H Westin, Roger B Cohen
PURPOSE: This first-in-human report examined the recommended Phase 2 dose and schedule of litronesib, a selective allosteric kinesin Eg5 inhibitor. METHODS: Two concurrent dose-escalation studies investigated litronesib across the dose range of 0.125-16 mg/m(2)/day, evaluating the following schedules of administration on a 21-day cycle: Days 1, 2, 3; Days 1, 5, 9; Days 1, 8; Days 1, 5; or Days 1, 4, with or without pegfilgrastim. Best overall response was defined per Response Evaluation Criteria in Solid Tumors (RECIST Version 1...
January 17, 2017: Cancer Chemotherapy and Pharmacology
Samer Tabchi, Normand Blais, Marie-Pierre Campeau, Mustapha Tehfe
PURPOSE: To date, the best chemotherapy regimen to combine with concurrent radiotherapy in stage III non-small-cell lung cancer remains undetermined. We compared the survival outcomes and toxicities in patients who were treated with etoposide-cisplatin (EP), paclitaxel-carboplatin (PC), or vinblastine-cisplatin (VP) in one large cancer referral center. METHODS: We enrolled patients who received concurrent chemoradiotherapy at our university-affiliated hospital between January 1, 2009 and December 31, 2013...
January 12, 2017: Cancer Chemotherapy and Pharmacology
Angelica L Quartino, Hanbin Li, Jin Y Jin, D Russell Wada, Mark C Benyunes, Virginia McNally, Lucia Viganò, Ihsan Nijem, Bert L Lum, Amit Garg
PURPOSE: The NeoSphere trial evaluated pertuzumab in the neoadjuvant setting [early breast cancer (EBC)] with pathological complete response (pCR) as the primary efficacy end point. This analysis of pertuzumab aimed to (1) compare its pharmacokinetics (PK) in patients with EBC versus advanced cancers, (2) to further evaluate PK drug-drug interactions (DDIs) when given in combination with trastuzumab, and (3) to assess the relationship between exposure and efficacy to assess the clinical dosing regimen in the EBC patients...
January 10, 2017: Cancer Chemotherapy and Pharmacology
Ian Joseph Cohen
No abstract text is available yet for this article.
January 9, 2017: Cancer Chemotherapy and Pharmacology
Hong-Yan Zhang, Feng Liang, Jian-Wei Zhang, Fei Wang, Li Wang, Xi-Gang Kang
PURPOSE: To explore how long noncoding RNA-ROR (lncRNA-ROR) affects the tamoxifen resistance of breast cancer cells. METHODS: Breast epithelial (MCF10A), breast cancer (MCF7), and natural tamoxifen-resistant breast cancer (MDA-MB-231) cell lines were selected, and the relative lncRNA-ROR expressions were detected using quantitative real-time polymerase chain reaction (qRT-PCR). In vitro induction of TR5 cell line was performed. There were six groups: MCF7, MCF7/TR5, MDA-MB-231, MCF7-ROR, MCF7/TR5 ROR-siRNA, and the MDA-MB-231 ROR-siRNA groups...
January 6, 2017: Cancer Chemotherapy and Pharmacology
Sarah Cargnin, Salvatore Terrazzino
No abstract text is available yet for this article.
January 6, 2017: Cancer Chemotherapy and Pharmacology
John Sarantopoulos, Alain C Mita, Aiwu He, James L Wade, Chung-Tsen Hsueh, John C Morris, A Craig Lockhart, David I Quinn, Jimmy Hwang, James Mier, Wenping Zhang, Claudine Wack, Jian Yin, Pierre-François Clot, Olivier Rixe
PURPOSE: Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. METHODS: Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/m(2), respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs)...
January 5, 2017: Cancer Chemotherapy and Pharmacology
Manikandan Alagumuthu, Sivakumar Arumugam
PURPOSE: Substituted 2-(4-phenylquinolin-2-yl) phenols (PQPDs) emerged as the inhibitors of phosphoinositide 3-kinase (PI3K) and anticancer agents. METHOD: PI3K inhibition was assessed by competitive ELISA. Anticancer activity was evaluated against breast cancer (MCF-7), skin cancer (G-361), and colon cancer (HCT 116) cell lines. RESULTS: In PI3 Kinase assay, PQPDs 4c, 4d, and 4k were inactive with IC50 >5 µM. IC50 for 4a, 4b, 4f-h, and 4j was ≥0...
January 4, 2017: Cancer Chemotherapy and Pharmacology
Frank M Balis, Patrick A Thompson, Yael P Mosse, Susan M Blaney, Charles G Minard, Brenda J Weigel, Elizabeth Fox
PURPOSE: Characterize the pharmacokinetics of oral crizotinib in children with cancer. METHODS: Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m(2)/dose administered twice daily. Two capsule and two oral liquid formulations were used over the course of the trial...
December 28, 2016: Cancer Chemotherapy and Pharmacology
Muhammad Wasif Saif, Andrew Heaton, Kimberley Lilischkis, James Garner, David M Brown
PURPOSE: Recurrent, chemo-resistant ovarian cancer is thought to be due to a subgroup of slow-growing, drug-resistant cancer cells with stem-like properties and a high capacity for tumour repair. Cantrixil targets this sub-population of cells and is being developed as an intraperitoneal therapy to be used as first-line therapy in combination with carboplatin for epithelial ovarian cancer. The studies presented here justify further development. METHODS: A GLP dog CV study using a 4 × 4 Latin Square Crossover study was conducted using telemetric ECG recordings from dogs post IP administration to assess for cardiac abnormalities...
December 24, 2016: Cancer Chemotherapy and Pharmacology
Janet K Coller, Joanne M Bowen, Imogen A Ball, Hannah R Wardill, Ysabella Z A van Sebille, Romany L Stansborough, Zenab Lightwala, Anthony Wignall, Joseph Shirren, Kate Secombe, Rachel J Gibson
PURPOSE: Irinotecan-induced gut toxicity is mediated in part by Toll-Like receptor 4 (TLR4) signalling. The primary purpose of this preclinical study was to determine whether blocking TLR4 signalling by administering (-)-naloxone, a TLR4 antagonist, would improve irinotecan-induced gut toxicity. Our secondary aim was to determine the impact of (-)-naloxone on tumour growth. METHODS: Female Dark Agouti (DA) tumour-bearing rats were randomly assigned to four treatments (n = 6 in each); control, (-)-naloxone (100 mg/kg oral gavage at -2, 24, 48, and 72 h), irinotecan (175 mg/kg intraperitoneal at 0 h), and (-)-naloxone and irinotecan...
December 23, 2016: Cancer Chemotherapy and Pharmacology
Ji Young Lee, Cheryn Song, Bum Sik Hong, Jun Hyuk Hong, Hanjong Ahn, Jae Lyun Lee
PURPOSE: The standard regimen of high-dose interleukin-2 (HDIL-2) for metastatic renal cell carcinoma (RCC) is two cycles separated by 9 days, which constitutes one course. Each course is separated by an 8-12 weeks. However, the 9-day interval between each HDIL-2 cycle is often not long enough to allow recovery from adverse effects. Therefore, we modified HDIL-2 schedules by increasing the interval between each cycle without changing the total cumulative doses of IL-2. METHODS: Clinical data from 37 patients who were treated with modified HDIL-2 schedule were reviewed...
December 23, 2016: Cancer Chemotherapy and Pharmacology
Kyoichi Kaira, Yoshio Tomizawa, Hisao Imai, Reiko Sakurai, Masana Matsuura, Akihiro Yoshii, Mai Ochiai, Mie Kotake, Takeshi Ebara, Jun-Ichi Saitoh, Noriaki Sunaga, Koichi Minato, Ryusei Saito, Takeshi Hisada
BACKGROUND: The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC). METHODS: Weekly nab-paclitaxel plus carboplatin was administered intravenously for 6 weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 60/2; level 3, 80/2 (nab-paclitaxel [mg/m(2)]/carboplatin [area under the plasma concentration time curve mg/ml/min])...
December 19, 2016: Cancer Chemotherapy and Pharmacology
Kim Dao, Yimin Lu, Cody J Peer, William D Figg, Raphael Stadelmann, Michel Burnier, Thierry Buclin, Sebastien Kissling
INTRODUCTION: High cut-off dialysis, increasingly used in multiple myeloma patients, is susceptible to influence anticancer drug elimination. We report about lenalidomide disposition in a patient on high cut-off dialysis for renal failure secondary to myeloma cast nephropathy. METHODS: The patient received a higher dosage of lenalidomide (5 mg b.i.d.), owing to concerns about a potential decrease in lenalidomide exposure during dialysis sessions. A set of blood samples was taken in order to develop a pharmacokinetic model accounting for lenalidomide concentrations in this setting...
December 17, 2016: Cancer Chemotherapy and Pharmacology
Margarita B Belogurova, Zoryana P Kizyma, Miklós Garami, Mónika Csóka, Michael J Lamson, Anton Buchner, Peter Bias, Andreas Lammerich
PURPOSE: Neutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose of lipegfilgrastim and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy...
December 16, 2016: Cancer Chemotherapy and Pharmacology
Hironaga Satake, Masaaki Iwatsuki, Yoshikazu Uenosono, Takeshi Shiraishi, Hiroaki Tanioka, Hiroshi Saeki, Keishi Sugimachi, Dai Kitagawa, Mototsugu Shimokawa, Eiji Oki, Yasunori Emi, Yoshihiro Kakeji, Akihito Tsuji, Yoshito Akagi, Shoji Natsugoe, Hideo Baba, Yoshihiko Maehara
PURPOSE: Capecitabine plus cisplatin (XP) is a standard therapy for metastatic gastric cancer (mGC). However, while results from previous phase III trials suggested that the cisplatin dosage should be reduced in Japanese patients, no clinical data exist to support this. Here, we conducted a multicenter study to evaluate the efficacy and safety of modified XP (mXP) in Japanese patients with mGC. METHODS: Patients with previously untreated mGC received mXP (cisplatin 60 mg/m(2) on day 1 plus capecitabine 1000 mg/m(2) twice daily on days 1-14) every 3 weeks...
December 10, 2016: Cancer Chemotherapy and Pharmacology
Jan S Moreb, Deniz A Ucar-Bilyeu, Abdullah Khan
A large number of studies have investigated possible drug resistance mechanisms of cancer cells and suggested strategies to overcome it. In this review, we outline the role and function of aldehyde dehydrogenase (ALDH) activity in multiple cellular functions and in cancer stem cells (CSCs) and focus on the role of retinoic acid (RA), one of the products of ALDH isozymes. We discuss our observation that ATRA and other RAs can suppress ALDH activity and decrease different ALDH isozyme proteins and result in detrimental effects on cell proliferation, invasion and chemotherapy sensitivity...
December 10, 2016: Cancer Chemotherapy and Pharmacology
Changhoon Yoo, Hyungwoo Cho, Min Jeong Song, Seung-Mo Hong, Kyu-Pyo Kim, Heung-Moon Chang, Heejung Chae, Tae Won Kim, Yong Sang Hong, Min-Hee Ryu, Yoon-Koo Kang, Song Cheol Kim, Baek-Yeol Ryoo
PURPOSE: Efficacy of targeted agents, such as everolimus and sunitinib, has been demonstrated in prospective trials on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Considering the heterogeneous clinicopathological characteristics of neuroendocrine tumors (NETs), evaluation of treatment outcomes in a real-world setting is necessary. METHODS: Clinical records of 44 patients with GEP-NET who were treated with everolimus or sunitinib between March 2007 and October 2014 were retrospectively reviewed...
December 10, 2016: Cancer Chemotherapy and Pharmacology
Shunji Takahashi, Takayuki Kobayashi, Junichi Tomomatsu, Yoshinori Ito, Hisanobu Oda, Tatsuhiro Kajitani, Tomoyuki Kakizume, Takeshi Tajima, Hiromi Takeuchi, Heiko Maacke, Taito Esaki
PURPOSE: Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients...
December 9, 2016: Cancer Chemotherapy and Pharmacology
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