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Cancer Chemotherapy and Pharmacology

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https://www.readbyqxmd.com/read/27904955/etirinotecan-pegol-administration-is-associated-with-lower-incidences-of-neutropenia-compared-to-irinotecan-administration
#1
S Kenneth Sy, Theresa D Sweeney, Chunmei Ji, Ute Hoch, Michael A Eldon
PURPOSE: The relationship between incidences of neutropenia and 10-hydroxy-7-ethyl camptothecin (SN38) exposure was explored using SN38 pharmacokinetic and neutrophil count data from toxicology studies of etirinotecan pegol (EP) and irinotecan in beagle dogs. METHODS: Dogs received four weekly intravenous infusions of either vehicle control (n = 22), EP (6, 15, 20, 25, 40/25 mg/kg; n = 3-9 dogs/dose group/sex; n = 48), or irinotecan (20 or 25 mg/kg n = 3-4 dogs/dose group/sex; n = 14)...
November 30, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27900441/successful-afatinib-treatment-of-advanced-non-small-cell-lung-cancer-patients-undergoing-hemodialysis
#2
Hisao Imai, Kyoichi Kaira, Ichiro Naruse, Hideki Hayashi, Hirotoshi Iihara, Yutaro Kita, Naoki Mizusaki, Takayuki Asao, Yoshinori Itoh, Tadashi Sugiyama, Koichi Minato, Masanobu Yamada
The treatment for patients with lung cancer undergoing hemodialysis, who are frequently elderly and have poor performance status, becomes a more important subject. However, the feasibility of afatinib in patients with chronic renal failure undergoing hemodialysis has not, so far, been reported. Here, afatinib was administered to three patients with NSCLC harboring EGFR mutation and chronic renal failure undergoing hemodialysis. Pharmacokinetic (PK) data of afatinib supported the safety of afatinib treatment...
November 29, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27889812/research-progress-of-hydroxychloroquine-and-autophagy-inhibitors-on-cancer
#3
REVIEW
Ting-Ting Shi, Xiao-Xu Yu, Li-Jun Yan, Hong-Tao Xiao
PURPOSE: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed. METHODS: A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study...
November 26, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878359/long-noncoding-rna-gas5-inhibits-malignant-proliferation-and-chemotherapy-resistance-to-doxorubicin-in-bladder-transitional-cell-carcinoma
#4
Hui Zhang, Yan Guo, Yongsheng Song, Chao Shang
PURPOSE: Bladder cancer is the most general malignant cancer in genitourinary system, more than 90% of BCs are bladder transitional cell carcinomas (BTCC). This study aimed to investigate the clinical significance of growth arrest-specific 5 (GAS5) gene and its regulatory effects of malignant proliferation and chemotherapy resistance to doxorubicin in BTCC cells. METHODS: The expression of GAS5 was detected by quantitative real-time PCR. Statistical analysis was used to determine the relationship between GAS5 expression and clinical features and the prognostic value of GAS5 for disease free survival...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878358/clinical-research-on-rare-diseases-of-children-neuroblastoma
#5
REVIEW
Chiara Gerardi, Rita Banzi, Vittorio Bertele', Silvio Garattini
PURPOSE: Early access to new treatment options should not preclude accurate research planning, especially for rare diseases and fragile populations. Taking neuroblastoma as a model case, we analyzed the rationale supporting the search for future therapeutic strategies in the light of preclinical and clinical evidence. METHODS: We reviewed ongoing randomized trials of pharmacological interventions for the treatment of neuroblastoma retrieved by searching ClinicalTrials...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878357/on-treatment-markers-as-predictors-to-guide-anti-egfr-moab-treatment-in-metastatic-colorectal-cancer-a-systematic-review-with-meta-analysis
#6
REVIEW
Jing Hu, Zhen Zhang, Rui Zheng, Lei Cheng, Mi Yang, Li Li, Baorui Liu, Xiaoping Qian
PURPOSE: Skin toxicity (ST) and early tumor shrinkage (ETS) are early phenomenon during the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) treatment. We conducted a meta-analysis and included relevant studies that reported the impact of ST and ETS on survival- and life quality-based outcome of metastatic colorectal cancer (mCRC) patients treated with anti-EGFR MoAb. METHODS: Relevant studies were identified from PubMed and Embase reporting the correlation of ST and ETS with the clinical outcome of mCRC patients treated with anti-EGFR MoAb...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878356/phase-i-trial-of-daily-triapine-in-combination-with-cisplatin-chemotherapy-for-advanced-stage-malignancies
#7
Charles A Kunos, Edward Chu, Jan H Beumer, Mario Sznol, S Percy Ivy
PURPOSE: Advanced-stage malignancies have increased deoxyribonucleotide demands in DNA replication and repair, making deoxyribonucleotide supply a potential exploitable target for therapy based on ribonucleotide reductase (RNR) inhibition. METHODS: A dose-finding phase I trial was conducted of intravenous (i.v.) triapine, a small-molecule RNR inhibitor, and cisplatin chemotherapy in patients with advanced-stage solid tumor malignancies. Patients received dose-finding levels of i...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878355/survival-impact-of-neoadjuvant-gemcitabine-plus-s-1-chemotherapy-for-patients-with-borderline-resectable-pancreatic-carcinoma-with-arterial-contact
#8
Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Naru Kondo, Naoya Nakagawa, Shinya Takahashi, Taijiro Sueda
PURPOSE: The aim of this study was to evaluate the efficacy of neoadjuvant gemcitabine plus S-1 (GS) chemotherapy as measured by overall survival for patients with pancreatic carcinoma with arterial contact. METHODS: Medical records of 77 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection were analyzed retrospectively. These patients were divided into two groups: patients who underwent upfront surgery and patients who underwent tumor resection after neoadjuvant GS chemotherapy...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27878354/randomized-phase-ii-study-of-cetuximab-versus-irinotecan-and-cetuximab-in-patients-with-chemo-refractory-kras-codon-g13d-metastatic-colorectal-cancer-g13d-study
#9
Masato Nakamura, Toru Aoyama, Keiichiro Ishibashi, Akihito Tsuji, Yasutaka Takinishi, Yoshiaki Shindo, Junichi Sakamoto, Koji Oba, Hideyuki Mishima
PURPOSE: This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation. PATIENTS AND METHODS: An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study comparing the cetuximab alone group (Cet group) and the combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27872953/a-phase-i-study-of-afatinib-combined-with-paclitaxel-and-bevacizumab-in-patients-with-advanced-solid-tumors
#10
James Spicer, Sheeba Irshad, Joo Ern Ang, Deborah Enting, Rebecca Kristeleit, Martina Uttenreuther-Fischer, Karine Pemberton, Katy Pelling, David Schnell, Johann de Bono
PURPOSE: The combination of afatinib, an irreversible ErbB family blocker, with paclitaxel and bevacizumab was assessed in patients with advanced solid tumors. METHODS: This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab. Safety, pharmacokinetics, and anti-tumor activity were also assessed. The starting dose was oral afatinib 40 mg once daily plus intravenous paclitaxel (fixed dose 80 mg/m(2), Days 1, 8, and 15 of a 4-week cycle) and intravenous bevacizumab 5 mg/kg every 2 weeks...
November 21, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27866244/efficacy-and-safety-of-nab-paclitaxel-in-patients-with-previously-treated-metastatic-colorectal-cancer-a-phase-ii-colo-001-trial
#11
Michel Ducreux, Jaafar Bennouna, Antoine Adenis, Thierry Conroy, Astrid Lièvre, Fabienne Portales, Julie Jeanes, Li Li, Alfredo Romano
PURPOSE: This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in pretreated patients with metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125 mg/m(2) days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator-assessed progression-free survival (PFS) rate at week 8; secondary endpoints included overall survival, overall response rate, and safety. Stage 1 planned enrollment was 15 patients per cohort per Simon 2-stage design...
November 19, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27837257/enhanced-anti-tumour-activity-of-the-combination-of-the-novel-mek-inhibitor-wx-554-and-the-novel-pi3k-inhibitor-wx-037
#12
Emma J Haagensen, Huw D Thomas, Wolfgang A Schmalix, Andrew C Payne, Lara Kevorkian, Rodger A Allen, Paul Bevan, Ross J Maxwell, David R Newell
PURPOSE: Tumours frequently have defects in multiple oncogenic pathways, e.g. MAPK and PI3K signalling pathways, and combinations of targeted therapies may be required for optimal activity. This study evaluated the novel MEK inhibitor WX-554 and the novel PI3K inhibitor WX-037, as single agents and in combination, in colorectal carcinoma cell lines and tumour xenograft-bearing mice. METHODS: In vitro growth inhibition, survival and signal transduction were measured using the Sulforhodamine B, clonogenic and Western blotting assays, respectively, in HCT116 and HT29 cell lines...
November 11, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27837256/pharmacokinetics-immunogenicity-and-safety-of-weekly-dosing-of-brentuximab-vedotin-in-pediatric-patients-with-hodgkin-lymphoma
#13
Jamie E Flerlage, Monika L Metzger, Jianrong Wu, John C Panetta
PURPOSE: Because of the observed success of phase I/II trials, the novel anti-CD30 agent brentuximab vedotin is now being evaluated as a frontline agent in the high-risk pediatric Hodgkin lymphoma trial HLHR13. The objectives of this study were to evaluate the pharmacokinetic variability during weekly dosing of 1.2 mg/kg of brentuximab vedotin, determine factors that may explain this variability, compare our drug exposure with published data, and evaluate toxicity of brentuximab vedotin in the pediatric population...
November 11, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27832327/dose-dense-paclitaxel-plus-carboplatin-as-neoadjuvant-chemotherapy-for-advanced-ovarian-fallopian-tube-or-primary-peritoneal-carcinomas
#14
T Ebata, M Yunokawa, S Bun, A Shimomura, T Shimoi, M Kodaira, K Yonemori, C Shimizu, Y Fujiwara, T Kato, K Tamura
PURPOSE: Weekly dose-dense paclitaxel with carboplatin every 3 weeks (dose-dense TC) provides good efficacy, and neoadjuvant chemotherapy is common for advanced-stage disease. However, it is unclear the efficacy and safety of dose-dense TC as neoadjuvant chemotherapy. Therefore, we evaluated neoadjuvant dose-dense TC chemotherapy for advanced-stage ovarian carcinoma. METHODS: We retrospectively reviewed cases of ovarian carcinoma that were not suited for primary debulking surgery (2003-2014)...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27832326/silencing-of-histone-deacetylase-2-suppresses-malignancy-for-proliferation-migration-and-invasion-of-glioblastoma-cells-and-enhances-temozolomide-sensitivity
#15
Zhiqiang Zhang, Yunmin Wang, Jiehan Chen, Qijia Tan, Caijun Xie, Cong Li, Wengang Zhan, Mei Wang
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27830320/pilot-study-of-fmc-5-fluorouracil-mitomycin-c-and-cisplatin-with-radiotherapy-for-patients-with-anal-cancer
#16
In Hee Lee, Soo Jung Lee, Byung Woog Kang, Yee Soo Chae, Dongwon Baek, Soyoon Hwang, Hye Jin Kim, Su Yeon Park, Jun Seok Park, Gyu Seog Choi, Jae Chul Kim, Jong Gwang Kim
OBJECTIVES: Concurrent chemoradiotherapy (CRT) is the current standard of treatment for anal squamous carcinoma. However, local or metastatic recurrences remain significant after CRT with 5-fluorouracil (5-FU) and mitomycin C (MMC). Therefore, the present study evaluated the feasibility and efficacy of adding cisplatin to the classic CRT (5-FU, MMC, and radiotherapy). METHODS: Twenty patients with histologically confirmed squamous cell carcinoma of the anus without metastatic disease were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between January 2005 and December 2014...
November 9, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27826729/pharmacodynamic-study-of-the-oral-hedgehog-pathway-inhibitor-vismodegib-in-patients-with-metastatic-castration-resistant-prostate-cancer
#17
Benjamin L Maughan, Daniel L Suzman, Brandon Luber, Hao Wang, Stephanie Glavaris, Robert Hughes, Rana Sullivan, Rana Harb, Karim Boudadi, Channing Paller, Mario Eisenberger, Angelo Demarzo, Ashely Ross, Emmanuel S Antonarakis
PURPOSE: Hedgehog (Hh) pathway signaling has been implicated in prostate cancer tumorigenesis and metastatic development and may be upregulated even further in the castration-resistant state. We hypothesized that antagonism of the Hh pathway with vismodegib in men with metastatic castration-resistant prostate cancer (mCRPC) would result in pathway engagement, inhibition and perhaps induce measurable clinical responses in patients. METHODS: This is a single-arm study of oral daily vismodegib in men with mCRPC...
November 8, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27817059/-18-f-flt-pet-ct-imaging-in-patients-with-advanced-solid-malignancies-treated-with-axitinib-on-an-intermittent-dosing-regimen
#18
Matthew Scarpelli, Justine Yang Bruce, Lakeesha Carmichael, Jens Eickhoff, Jill Kolesar, Scott Perlman, Robert Jeraj, Glenn Liu
PURPOSE: This study utilizes FLT PET/CT imaging to characterize changes in tumor cell proliferation and vasculature during intermittent treatment with VEGR-TKI axitinib. METHODS: Patients with metastatic solid malignancies underwent 3-week treatment cycles with axitinib (7 and 5 mg BID for safety and pharmacodynamic cohorts, respectively). Cycles consisted of 2 weeks of treatment (dosing period) followed by a 1-week treatment break (washout period). Patients in the pharmacodynamic cohort had up to six FLT PET/CT scans (three scans in each cycle 1 and cycle 3) and had plasma VEGF concentrations measured at imaging timepoints...
November 5, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27807652/pharmacokinetic-dose-adjustment-of-5-fu-in-modified-folfox7-plus-bevacizumab-for-metastatic-colorectal-cancer-in-japanese-patients-a-just-phase-ii-clinical-trial
#19
Tadamichi Denda, Mitsuro Kanda, Yoshitaka Morita, Ho Min Kim, Tomomi Kashiwada, Chu Matsuda, Shinji Fujieda, Ken Nakata, Kenta Murotani, Koji Oba, Junichi Sakamoto, Hideyuki Mishima
PURPOSE: Dose adjustment of 5-fluorouracil (FU) based on pharmacokinetic monitoring has been shown to reduce toxicities and increase efficacy compared with dosing based on body surface area in patients with metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of pharmacokinetic dose adjustment of FU in a modified FOLFOX7 (mFOLFOX7) plus bevacizumab regimen in Japanese patients with previously untreated mCRC. METHODS: This single-arm, multicenter phase II trial enrolled 48 patients with mCRC...
November 2, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27796540/effects-of-elotuzumab-on-qt-interval-and-cardiac-safety-in-patients-with-multiple-myeloma
#20
Chaitali Passey, Raymond Darbenzio, Ying-Ming Jou, Mark Lynch, Manish Gupta
PURPOSE: To assess the effect of elotuzumab on corrected QT (QTc) intervals and cardiac safety. METHODS: Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (treatment cycles 1-3). ECG intervals and changes relative to baseline were assessed. The key ECG endpoint was change from baseline in QT interval corrected with Fridericia's method (ΔQTcF)...
October 28, 2016: Cancer Chemotherapy and Pharmacology
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