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Cancer Chemotherapy and Pharmacology

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https://www.readbyqxmd.com/read/29330636/a-randomised-trial-comparing-the-pharmacokinetics-and-safety-of-the-biosimilar-ct-p6-with-reference-trastuzumab
#1
Francisco J Esteva, Justin Stebbing, Rebecca N Wood-Horrall, Peter J Winkle, Sung Young Lee, Sang Joon Lee
PURPOSE: Access to trastuzumab, a valuable anti-cancer treatment, can be limited by cost. The primary aim of this study was to evaluate and compare the PK profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference trastuzumab (Herceptin®) in healthy subjects. Secondary study aims included comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in these subjects. METHODS: We performed a single-dose, randomised, double-blind, parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6 mg/kg, 90 min intravenous infusion) in 70 healthy adult males...
January 12, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29327274/first-line-therapy-for-advanced-non-small-cell-lung-cancer-with-activating-egfr-mutation-is-combined-egfr-tkis-and-chemotherapy-a-better-choice
#2
REVIEW
Shuyun Wang, Aiqin Gao, Jie Liu, Yuping Sun
As the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the median progression-free survival (PFS) up to 18.9 months. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, which limits the first-line PFS. To overcome the resistance and improve overall survival, researchers have tried to identify the resistance mechanisms and develop new treatment strategies, among which a combination of EGFR-TKIs and cytotoxic chemotherapy is one of the hotspots...
January 11, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29322231/the-effect-of-food-on-the-pharmacokinetics-of-niraparib-a-poly-adp-ribose-polymerase-parp-inhibitor-in-patients-with-recurrent-ovarian-cancer
#3
Kathleen Moore, Zhi-Yi Zhang, Shefali Agarwal, Howard Burris, Manish R Patel, Vikram Kansra
PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. In this open-label crossover study, we evaluated the effects of food on niraparib pharmacokinetics (PK) and safety. METHODS: Patients received a single 300-mg dose of niraparib either after a high-fat meal or under fasting conditions...
January 10, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29313067/combinatorial-effects-of-histone-deacetylase-inhibitors-hdaci-vorinostat-and-entinostat-and-adaphostin-are-characterized-by-distinct-redox-alterations
#4
Nilsa Rivera-Del Valle, Tiewei Cheng, Mary E Irwin, Hayley Donnella, Melissa M Singh, Joya Chandra
PURPOSE: Amongst the epigenetically targeted therapies, targeting of the histone deacetylases (HDACs) has yielded numerous drugs for clinical use in hematological malignancies, but none as yet for acute lymphocytic leukemia (ALL). Single agent activity of HDAC inhibitors (HDACi) has been elusive in ALL, and has prompted study of combinatorial strategies. Because several HDACi raise levels of intracellular oxidative stress, we evaluated combinations of two structurally distinct HDACi with the redox active compound adaphostin in ALL...
January 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29313066/retraction-note-to-quinoxaline-1-4-dioxides-induce-g2-m-cell-cycle-arrest-and-apoptosis-in-human-colon-cancer-cells
#5
Hala U Gali-Muhtasib, Mona Diab-Assaf, Makhluf J Haddadin
The authors have retracted this article because of overlap in images within the publication and with another previously published article. It was brought to our attention that there are inconsistencies in Figs. 3, 5 and 6. The left middle panel in Fig. 3, labeled "Ctrl", is the same as the left panel in Fig. 6, labeled "PD98059", except that the latter is flipped upside down and right-left. In Fig. 5, the gel in the middle left panel labeled TGF-β2 has been cropped in two different ways and used in Figs...
January 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29308536/rabdocoestin-b-exhibits-antitumor-activity-by-inducing-g2-m-phase-arrest-and-apoptosis-in-esophageal-squamous-cell-carcinoma
#6
Jingnan Wang, Zhirong Zhang, Yun Che, Zuyang Yuan, Zhiliang Lu, Yuan Li, Jun Wan, Handong Sun, Zhaoli Chen, Jianxin Pu, Jie He
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated. METHODS: The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry...
January 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29305639/a-phase-i-study-for-adjuvant-chemotherapy-of-gemcitabine-plus-s-1-in-patients-with-biliary-tract-cancer-undergoing-curative-resection-without-major-hepatectomy-khbo1202
#7
Hiroaki Yanagimoto, Hideyoshi Toyokawa, Daisuke Sakai, Hiroshi Wada, Sohei Satoi, Tomohisa Yamamoto, Hiroaki Nagano, Masanori Toyoda, Tetsuo Ajiki, Hironaga Satake, Akihito Tsuji, Atsushi Miyamoto, Masanori Tsujie, Shigekazu Takemura, Kazuhiro Yanagihara, Tatsuya Ioka
PURPOSE: To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy. METHODS: A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m2) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2)...
January 5, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29305638/pharmacokinetics-of-dacarbazine-dtic-in-pregnancy
#8
Ira Kantrowitz-Gordon, Karen Hays, Olumide Kayode, Aditya R Kumar, Henry G Kaplan, Joel M Reid, Stephanie L Safgren, Matthew M Ames, Thomas R Easterling, Mary F Hebert
PURPOSE: The purpose of this report is to describe, for the first time, the pharmacokinetics of dacarbazine (DTIC) and its metabolites [5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC), 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-aminoimidazole-4-carboxamide (AIC)] during pregnancy (n = 2) and postpartum (n = 1). METHODS: Non-compartmental DTIC, MTIC, HMMTIC, and AIC pharmacokinetics (PK) were estimated in one case at 29 week gestation and 18 day postpartum and a second case at 32 week gestation, in women receiving DTIC in combination with doxorubicin, bleomycin, and vinblastine for treatment of Hodgkin's lymphoma...
January 5, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29299639/b7-h3-in-tumors-friend-or-foe-for-tumor-immunity
#9
REVIEW
Gen Li, Yanchun Quan, Fengyuan Che, Lijuan Wang
B7-H3 is a type I transmembrane co-stimulatory molecule of the B7 family. B7-H3 mRNA is widely distributed in most tissues; however, B7-H3 protein is not constitutively expressed. Few molecules have been shown to mediate the regulation of B7-H3 expression, and their regulatory mechanisms remain unexplored. Recently, TREM-like transcript 2 (TLT-2) has been identified as a potential receptor of B7-H3. However, TLT-2 may not be the only receptor of B7-H3, as B7-H3 has many contradictory roles. As a co-stimulatory molecule, B7-H3 increases the proliferation of both CD4+ and CD8+ T-cells and enhances cytotoxic T-cell activity...
January 3, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29299638/prediction-of-neutrophil-reduction-using-plasma-paclitaxel-concentration-after-administration-in-patients-with-uterine-ovarian-or-cervical-cancers-in-an-outpatient-clinic
#10
Motoaki Ishikawa, Michiyasu Kawai, Toshio Maeda, Yoshiyuki Kagawa
PURPOSE: Plasma paclitaxel (PTX) concentration 24 h or later after PTX administration may predict myelosuppression. Here, we explored predictive markers for neutropenia induced by intravenous administration of PTX in an outpatient clinic. METHODS: Thirty women suffering from uterine, ovarian or cervical cancer were enrolled in this study. PTX (mean dose: 167 mg/m2) was intravenously infused and followed by carboplatin. Plasma samples were obtained 4 h after PTX administration...
January 3, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29294168/a-pilot-study-of-daunorubicin-augmented-hyper-cvad-induction-chemotherapy-for-adults-with-acute-lymphoblastic-leukemia
#11
Sung-Yong Kim, Ji Hyun Park, So Young Yoon, Yo-Han Cho, Mark Hong Lee
Induction of complete remission (CR) is imperative for long-term survival in adult acute lymphoblastic leukemia (ALL) patients regardless of transplantation eligibility. Hyper-CVAD chemotherapy is a widely-used frontline remission induction regimen for these patients. We conducted a pilot trial of frontline remission induction using daunorubicin-augmented hyper-CVAD regimen (hyper-CVDD) in adult ALL patients (n = 15). The CR rate after this modified regimen was 100% (n = 15). Twelve patients were able to proceed to allogeneic hematopoietic cell transplantation, two patients died before transplantation due to infection, and the remaining one who was ineligible for transplant due to her age received an additional five courses of consolidation chemotherapy...
January 2, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29290024/a-multi-institution-phase-ii-study-of-docetaxel-and-s-1-in-combination-with-trastuzumab-for-her2-positive-advanced-gastric-cancer-dash-study
#12
Shunsuke Kagawa, Atsushi Muraoka, Takeshi Kambara, Hiroshi Nakayama, Ryosuke Hamano, Norimitsu Tanaka, Kazuhiro Noma, Kohji Tanakaya, Hiroyuki Kishimoto, Kunitoshi Shigeyasu, Shinji Kuroda, Satoru Kikuchi, Kazuya Kuwada, Masahiko Nishizaki, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
BACKGROUND: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated. METHODS: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible...
December 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29290023/immunological-hallmarks-of-cis-ddp-resistant-lewis-lung-carcinoma-cells
#13
Olexandr Fedorchuk, Yaroslav Susak, Mariia Rudyk, Nataliia Senchylo, Nataliia Khranovska, Oksana Skachkova, Larysa Skivka
PURPOSE: Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated. METHODS: Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined...
December 30, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29285635/cellular-pharmacology-studies-of-anticancer-agents-recommendations-from-the-eortc-pamm-group
#14
REVIEW
Paola Perego, Georg Hempel, Stig Linder, Tracey D Bradshaw, Annette K Larsen, Godefridus J Peters, Roger M Phillips
An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumor agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible...
December 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29249039/advances-in-ovarian-cancer-therapy
#15
REVIEW
Alexander J Cortez, Patrycja Tudrej, Katarzyna A Kujawa, Katarzyna M Lisowska
Epithelial ovarian cancer is typically diagnosed at an advanced stage. Current state-of-the-art surgery and chemotherapy result in the high incidence of complete remissions; however, the recurrence rate is also high. For most patients, the disease eventually becomes a continuum of symptom-free periods and recurrence episodes. Different targeted treatment approaches and biological drugs, currently under development, bring the promise of turning ovarian cancer into a manageable chronic disease. In this review, we discuss the current standard in the therapy for ovarian cancer, major recent studies on the new variants of conventional therapies, and new therapeutic approaches, recently approved and/or in clinical trials...
December 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29242966/cyp1a1-genetic-polymorphism-is-a-promising-predictor-to-improve-chemotherapy-effects-in-patients-with-metastatic-breast-cancer-treated-with-docetaxel-plus-thiotepa-vs-docetaxel-plus-capecitabine
#16
Xinna Zhou, Guoliang Qiao, Xiaoli Wang, Qingkun Song, Michael A Morse, Amy Hobeika, William R Gwin, Jun Ren, H Kim Lyerly
PURPOSE: A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting clinical efficacy of these chemotherapies. METHODS: MBC patients (n = 130) were randomized to treatment with DT (n = 65) or DC (n = 65). Response rate, disease control rate, progression-free and overall survival were monitored...
December 14, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29238851/phase-i-ii-study-of-mocetinostat-in-combination-with-gemcitabine-for-patients-with-advanced-pancreatic-cancer-and-other-advanced-solid-tumors
#17
Emily Chan, E Gabriela Chiorean, Peter J O'Dwyer, Nashat Y Gabrail, Thierry Alcindor, Diane Potvin, Richard Chao, Herbert Hurwitz
PURPOSE: To evaluate the safety and efficacy of mocetinostat (a Class I/IV HDAC inhibitor) in combination with gemcitabine in patients with solid tumors, including pancreatic cancer. METHODS: In this open-label, non-randomized Phase I/II study (NCT00372437) sequential cohorts of patients with solid tumors received gemcitabine (1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) and oral mocetinostat [50-110 mg, three times per week (TIW)]. The maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) was determined based on dose-limiting toxicities in Cycle 1 (Phase I study)...
December 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29234922/pharmacokinetically-targeted-dosed-everolimus-maintenance-therapy-in-lymphoma-patients
#18
L K Schoch, A Asiama, M Zahurak, S Shanbhag, J Hurtt, K Sawyer, L J Swinnen, N Wagner-Johnston, R J Jones, R F Ambinder, Douglas E Gladstone
BACKGROUND: Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients. PATIENTS/METHODS: After HDC, everolimus was dosed to serum trough levels (goal 3-15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities...
December 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29234921/a-phase-ii-trial-of-ifosfamide-combination-with-recommended-supportive-therapy-for-recurrent-sclc-in-second-line-and-heavily-treated-setting
#19
Ichidai Tanaka, Kenji Kawada, Masahiro Morise, Tetsunari Hase, Hiroaki Hayashi, Akihiko Sokai, Asuki Fukatsu, Masashi Kondo, Fumio Nomura, Yoshinori Hasegawa
PURPOSE: The response rate of ifosfamide (IFM) monotherapy for small-cell lung cancer (SCLC) is reported as 42.4% in Japanese package insert. However, these efficacy data are based on clinical studies conducted in 1970s. This phase II study evaluated the efficacy and safety of IFM combination with recommended current supportive therapy for recurrent SCLC in second-line and heavily treated setting. METHODS: Recurrent SCLC patients pretreated with one to three prior regimens received IFM monotherapy (1...
December 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29230503/concordance-between-the-response-evaluation-criteria-in-solid-tumors-version-1-1-and-the-immune-related-response-criteria-in-patients-with-non-small-cell-lung-cancer-treated-with-nivolumab-a-multicenter-retrospective-cohort-study
#20
Yuki Kataoka, Katsuya Hirano, Tomoko Narabayashi, Satoshi Hara, Daichi Fujimoto, Tae Tanaka, Noriyuki Ebi, Keisuke Tomii, Hiroshige Yoshioka
PURPOSE: The immune-related response criteria (irRC) were proposed to incorporate pseudo-progression. However, the association between the irRC and overall survival (OS) has yet to be evaluated in non-small cell lung cancer (NSCLC). Therefore, the purpose of this study is to evaluate the concordance between the response evaluation criteria in solid tumors (RECIST) version 1.1 and the irRC in patients with NSCLC treated with nivolumab, as well as, to determine the relationship between these two response criteria and OS...
December 11, 2017: Cancer Chemotherapy and Pharmacology
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