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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/28739504/improved-metabolic-stability-and-therapeutic-efficacy-of-a-novel-molecular-gemcitabine-phospholipid-complex
#1
Chander Parkash Dora, Varun Kushwah, Sameer S Katiyar, Pradeep Kumar, Viness Pillay, Sarasija Suresh, Sanyog Jain
The aim of the present research is to increase lipid solubility, metabolic stability and therapeutic efficacy of water soluble gemcitabine (GEM) via phospholipid complex (PC) formation. A novel phospholipid complex of GEM was successfully prepared and optimized. Physical interaction of GEM with phospholipid was evaluated by DSC, FT-IR, (1)H NMR, (31)P-NMR and P-XRD. SEM images of GEM-PC showed rough structure and TEM images of diluted aqueous dispersion of GEM-PC showed micellar structure. In silico study also revealed the significant interaction between drug and phospholipid...
July 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28736643/comparison-of-efficacy-and-toxicity-of-folfirinox-and-gemcitabine-with-nab-paclitaxel-in-unresectable-pancreatic-cancer
#2
Tetsuhito Muranaka, Masaki Kuwatani, Yoshito Komatsu, Kentaro Sawada, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Satoshi Yuki, Yoshimasa Kubota, Kimitoshi Kubo, Shuhei Kawahata, Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
BACKGROUND: Irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) and the combination regimen of gemcitabine and nanoparticle albumin-bound paclitaxel (GnP) (nab-PTX) improve the prognosis of patients with metastatic pancreatic cancer. However, no study has compared the efficacy of the two regimens. We compared retrospectively the efficacy and safety of the two regimens in patients with unresectable pancreatic cancer. METHODS: Thirty-eight patients with unresectable locally advanced or metastatic pancreatic cancer received FOLFIRINOX or GnP as first-line chemotherapy between December 2013 and September 2015...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736642/gemcitabine-nab-paclitaxel-as-second-line-therapy-following-folfirinox-in-metastatic-advanced-pancreatic-cancer-retrospective-analysis-of-response
#3
Khanh T Nguyen, Aparna Kalyan, H Scott Beasley, Aatur D Singhi, Weijing Sun, Herbert J Zeh, Daniel Normolle, Nathan Bahary
BACKGROUND: Given the tolerability of nPG in first-line therapy, we desired to evaluate the response and toxicity profiles of second-line gemcitabine with nab-paclitaxel (nPG) following FOLFIRINOX. Methods: We retrospectively identified 30 patients who received first-line FOLFIRINOX for unresectable or metastatic pancreatic adenocarcinoma followed by second-line nPG. Response was evaluated by RECIST criteria and carbohydrate antigen 19-9 (CA19-9) change. RESULTS: Median age was 63 years with 77% percent having metastatic disease...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28722678/optimal-adjuvant-chemotherapy-for-resected-pancreatic-adenocarcinoma-a-systematic-review-and-network-meta-analysis
#4
Jian-Bo Xu, Bin Jiang, Ya Chen, Fu-Zhen Qi, Jian-Huai Zhang, Hang Yuan
Adjuvant chemotherapy improves survival in patients with resected pancreatic cancer but the optimal regimen remains unclear. We aim to compare all possible adjuvant chemotherapy in terms of overall survival and toxic effects. Pubmed, Trial registries and Cochrane library databases for randomized controlled trials were searched until November 2016. Thirteen trials were included for network analysis and the hazard ratios (HRs) for survival and odds ratios for toxic effects were assessed via Aggregate Data Drug Information System software...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722661/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#5
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722177/metformin-induced-alterations-in-nucleotide-metabolism-cause-5-fluorouracil-resistance-but-gemcitabine-susceptibility-in-oesophageal-squamous-cell-carcinoma
#6
Charissa Mynhardt, Leonard Howard Damelin, Rupal Jivan, Jade Peres, Sharon Prince, Robin Bruce Veale, Demetra Mavri-Damelin
5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than 5-fold and 6-fold respectively, as assessed by MTT assay...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28716944/potent-competitive-inhibition-of-human-ribonucleotide-reductase-by-a-nonnucleoside-small-molecule
#7
Md Faiz Ahmad, Intekhab Alam, Sarah E Huff, John Pink, Sheryl A Flanagan, Donna Shewach, Tessianna A Misko, Nancy L Oleinick, William E Harte, Rajesh Viswanathan, Michael E Harris, Chris Godfrey Dealwis
Human ribonucleotide reductase (hRR) is crucial for DNA replication and maintenance of a balanced dNTP pool, and is an established cancer target. Nucleoside analogs such as gemcitabine diphosphate and clofarabine nucleotides target the large subunit (hRRM1) of hRR. These drugs have a poor therapeutic index due to toxicity caused by additional effects, including DNA chain termination. The discovery of nonnucleoside, reversible, small-molecule inhibitors with greater specificity against hRRM1 is a key step in the development of more effective treatments for cancer...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28709705/phase-ii-trial-of-neoadjuvant-chemotherapy-followed-by-chemoradiation-in-locally-advanced-cervical-cancer
#8
Carla Rameri Alexandre Silva de Azevedo, Luiz Cláudio Santos Thuler, Maria Júlia Gonçalves de Mello, Jurema Telles de Oliveira Lima, Ana Luiza Fassizoli da Fonte, Diógenes Fernando Santos Fontão, Vandré Cabral Gomes Carneiro, Tien Man Cabral Chang, Carlos Gil Ferreira
OBJECTIVE: Cervical cancer is a global public health challenge. Since 1999, platin based chemoradiation (CRT) is the standard treatment for those patients with locally advanced disease. However, this population still has a dismal prognosis and, alternatives approaches such as adjuvant chemotherapy are controversial, especially because of increased toxicity. Neoadjuvant chemotherapy (NACT) could be an option for more intensive treatment with manageable toxicity. METHODS: A phase II, prospective, non-randomized trial was conducted at a reference center in Recife, Brazil...
July 11, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28708229/adjuvant-chemoradiotherapy-gemcitabine-based-in-pancreatic-adenocarcinoma-the-pisa-university-experience
#9
Aldo Sainato, Sabrina Montrone, Francesco Pasqualetti, Marianna Coppola, Nunzia L V Cernusco, Marco Panichi, Alessandra Gonnelli, Enrico Vasile, Riccardo Morganti, Alfredo Falcone, Ugo Boggi, Fabiola Paiar
INTRODUCTION: The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. METHODS: 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly)...
July 11, 2017: Tumori
https://www.readbyqxmd.com/read/28703890/targeted-therapies-in-pancreatic-cancer-promises-and-failures
#10
Matineh Barati Bagherabad, Fahimeh Afzaljavan, Soodabeh ShahidSales, Seyed Mahdi Hassanian, Amir Avan
Pancreatic ductal adenocarcinoma (PDAC) is an incidence rate nearly equal to its mortality rate. The poor prognosis of the disease can be explained by the absence of effective biomarkers for screening and early detection, together with the aggressive behavior and resistance to the currently available chemotherapy. The therapeutic failure can also be attributed to the inter-/intra- tumor genetic heterogeneity and the abundance of tumor stroma that occupies the majority of the tumor mass. Gemcitabine is used in the treatment of PDAC, however, the response rate is less than 12%...
July 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28702772/a-phase-ii-trial-of-erlotinib-monotherapy-in-advanced-pancreatic-cancer-as-a-first-or-second-line-agent
#11
Christos Fountzilas, Ravi Chhatrala, Nikhil Khushalani, Wei Tan, Charles LeVea, Alan Hutson, Chris Tucker, Wen Wee Ma, Graham Warren, Patrick Boland, Renuka Iyer
INTRODUCTION: Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy. METHODS: Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression...
July 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28695246/intensity-modulated-radiation-therapy-followed-by-gdp-chemotherapy-for-newly-diagnosed-stage-i-ii-extranodal-natural-killer-t-cell-lymphoma-nasal-type
#12
Yu Huang, Jianliang Yang, Peng Liu, Shengyu Zhou, Lin Gui, Xiaohui He, Yan Qin, Changgong Zhang, Sheng Yang, Puyuan Xing, Yan Sun, Yuankai Shi
Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy...
July 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28694765/cellular-uptake-and-anti-tumor-activity-of-gemcitabine-conjugated-with-new-amphiphilic-cell-penetrating-peptides
#13
Parvin Zakeri-Milani, Samad Mussa Farkhani, Ali Shirani, Samaneh Mohammadi, Javid Shahbazi Mojarrad, Jafar Akbari, Hadi Valizadeh
Gemcitabine (Gem) is used as a single agent or in combination with other anticancer agents to treat many types of solid tumors. However, it has many limitations such as a short plasma half-life, dose-limiting toxicities and drug resistance. Cell-penetrating peptides (CPPs) are short peptides which may deliver a large variety of cargo molecules into the cancerous cells. The current study was designed to evaluate the antiproliferative activity of gemcitabine chemically conjugated to CPPs. The peptides were synthesized using solid phase synthesis procedure...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28693283/prospective-exploratory-study-of-gemcitabine-and-s-1-against-elderly-patients-with-advanced-non-small-cell-lung-cancer
#14
Kyoichi Kaira, Noriko Yanagitani, Noriaki Sunaga, Hisao Imai, Akihiro Ono, Yasuhiko Koga, Takeshi Hisada, Tamotsu Ishizuka, Masanobu Yamada
A prospective study was conducted to investigate the efficacy of a combined regimen of gemcitabine and S-1 for the treatment of elderly patients (>70 years) with advanced non-small cell lung cancer (NSCLC) as a first-line setting based on the dosage recommended in a previous phase I study. Chemotherapy-naïve patients with advanced NSCLC received gemcitabine plus S-1. S-1 (40 mg/m(2)) was administered orally twice daily for 14 days while gemcitabine (1,000 mg/m(2)) was administered on days 1 and 15 of each cycle, and this regimen was repeated every 4 weeks...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687003/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#15
Kelli L Goss, Stacia L Koppenhafer, Kathryn M Harmoney, William W Terry, David J Gordon
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28685064/identification-of-rhodamine-123-positive-stem-cell-subpopulations-in-canine-hepatocellular-carcinoma-cells
#16
Harumichi Itoh, Shimpei Nishikawa, Tomoya Haraguchi, Yu Arikawa, Masato Hiyama, Toshie Iseri, Yoshiki Itoh, Munekazu Nakaichi, Yasuho Taura, Kenji Tani, Kazuhito Itamoto
The majority of cases of chemotherapy for hepatocellular carcinoma (HCC) are not effective in human or veterinary medicine due to resistance against anticancer agents. In human medicine, hepatocellular carcinoma stem cells (HCSCs) were recently identified as cytokeratin 19 (CK19)-, cluster of differentiation (CD)-44-, and CD133-positive. However, there are few previous reports regarding canine HCSC (cHCSC). Additionally, to the best of our knowledge, the chemoresistance against anticancer agents of these cHCSCs has not been investigated...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28681936/toxicity-of-chemotherapy-regimens-in-advanced-and-metastatic-pancreatic-cancer-therapy-a-network-meta-analysis
#17
Xiao-Fang Wang, Wen-Feng Huang, Jian Nie, Yong Zhou, Ding-Wu Tan, Ji-Hao Jiang
This network meta-analysis is adopted in order to compare the toxicity of different chemotherapy regimens in the treatment of advanced/metastatic pancreatic cancer (PC). Randomized controlled trials (RCTs) about different chemotherapy regimens for advanced/metastatic PC were included in this network meta-analysis using Cochrane Library and PubMed electronic databases. The network meta-analysis was performed to combine direct and indirect evidence in order to calculate the odd ratios (OR) and draw a surface under the cumulative ranking (SUCRA) curve...
July 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28668866/histology-based-combination-induction-chemotherapy-for-elderly-patients-with-clinical-stage-iii-non-small-cell-lung-cancer
#18
Giuseppe L Banna, Hector Josè Soto Parra, Marine Castaing, Maria Vittoria Dieci, Giuseppe Anile, Maurizio Nicolosi, Salvatore Strano, Francesco Marletta, Valentina Guarneri, Pierfranco Conte, Rohit Lal
AIM: To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666261/chemosensitivity-directed-therapy-compared-to-dacarbazine-in-chemo-naive-advanced-metastatic-melanoma-a-multicenter-randomized-phase-3-decog-trial
#19
Selma Ugurel, Carmen Loquai, Patrick Terheyden, Dirk Schadendorf, Erika Richtig, Jochen Utikal, Ralf Gutzmer, Knuth Rass, Cord Sunderkötter, Annette Stein, Michael Fluck, Martin Kaatz, Uwe Trefzer, Katharina Kähler, Rudolf Stadler, Carola Berking, Christoph Höller, Laura Kerschke, Lutz Edler, Annette Kopp-Schneider, Jürgen C Becker
Chemotherapy still plays an important role in metastatic melanoma, particularly for patients who are not suitable or have no access to highly efficacious new therapies. Pre-therapeutic chemosensitivity testing might be useful to identify optimal chemotherapy regimens for individual patients. This multicenter randomized phase-3 trial was aimed to test for superiority of chemosensitivity-directed combination chemotherapy compared to standard dacarbazine monochemotherapy, and to demonstrate the chemosensitivity test result as prognostic in metastatic melanoma...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28664225/does-optinab-strategy-stop-and-go-work-in-treatment-of-advanced-pancreatic-cancer-apc-with-nab-paclitaxel-gemcitabine
#20
Valerie Relias, Antonia Maloney, Melissa H Smith, Muhammad Wasif Saif
BACKGROUND: MPACT demonstrated a survival benefit of nab-paclitaxel plus gemcitabine versus gemcitabine in advanced pancreatic cancer (APC). However, sensory peripheral neuropathy is a dose-limiting toxicity and neuromodulators have shown limited, if any activity in ameliorating neuropathy. In colorectal cancer, the OPTIMOX ("stop-and-go") approach offered a strategy to reduce neuropathy. No data exist to support this strategy for nab-paclitaxel in APC. METHODS: Retrospective study of APC patients who developed grade 3 neuropathy during nab-paclitaxel plus gemcitabine was done...
June 29, 2017: Cancer Chemotherapy and Pharmacology
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