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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/28346313/population-pharmacokinetics-of-gemcitabine-and-dfdu-in-pancreatic-cancer-patients-using-an-optimal-design-sparse-sampling-approach
#1
Cindy Serdjebi, Florence Gattacceca, Jean-François Seitz, Francine Fein, Johan Gagnière, Eric François, Abakar Abakar-Mahamat, Gael Deplanque, Madani Rachid, Bruno Lacarelle, Joseph Ciccolini, Laetitia Dahan
BACKGROUND: Gemcitabine remains a pillar in pancreatic cancer treatment. However, toxicities are frequently observed. Dose adjustment based on therapeutic drug monitoring might help decrease the occurrence of toxicities. In this context, this work aims at describing the pharmacokinetics (PK) of gemcitabine and its metabolite dFdU in pancreatic cancer patients and at identifying the main sources of their PK variability using a population pharmacokinetics approach, despite a sparse sampled-population and heterogeneous administration and sampling protocols...
March 24, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28344661/liposomal-irinotecan-in-gemcitabine-refractory-metastatic-pancreatic-cancer-efficacy-safety-and-place-in-therapy
#2
REVIEW
Emma Kipps, Kate Young, Naureen Starling
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. The majority of patients are diagnosed with locally advanced or metastatic disease with a prognosis of short months. Therapeutic options are limited and until recently, there was no standard second-line chemotherapy option. Liposomal constructs have been engineered to encapsulate chemotherapy thereby preventing premature metabolism, improving distribution and minimizing toxicity. Favourable preclinical data on liposomal irinotecan and early phase trials, led to a recently published phase III trial of liposomal irinotecan in combination with fluorouracil and folinic acid in patients with metastatic PDAC, who progressed after gemcitabine-based chemotherapy...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344046/long-term-outcomes-of-induction-carboplatin-and-gemcitabine-followed-by-concurrent-radiotherapy-with-low-dose-paclitaxel-and-gemcitabine-for-stage-iii-non-small-cell-lung%C3%A2-cancer
#3
Catherine Guilbault, Aurelie Garant, Sergio Faria, Scott Owen, Linda Ofiara, Marie Duclos, Vera Hirsh, Neil Kopek
BACKGROUND: Standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemo-radiation (CRT). A regimen of induction carboplatin and gemcitabine followed by CRT was developed at the McGill University Health Centre to prevent delays in treatment initiation. We report the long-term outcomes with this regimen based on a pooled analysis of both protocol patients from a phase II study and nonprotocol patients. METHODS AND MATERIALS: Outcomes and toxicity data were retrieved for 142 patients with stage III NSCLC: 43 patients treated on protocol between January 2003 and November 2004, and 101 patients treated off-protocol between December 2004 and August 2013...
March 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28341958/randomized-phase-ii-study-comparing-weekly-docetaxel-cisplatin-vs-gemcitabine-cisplatin-in-elderly-or-poor-performance-status-patients-with-advanced-non-small-cell-lung-cancer
#4
JoungSoon Jang, Hoon-Kyo Kim, Byoung Chul Cho, Kyung Hee Lee, Hwan-Jung Yun, In Sook Woo, Hong Suk Song, Hun-Mo Ryoo, Chi-Hong Kim, Der-Sheng Sun, Jong Wook Shin
BACKGROUND: Docetaxel/cisplatin (DP) and gemcitabine/cisplatin (GP) are standard treatment regimens for advanced non-small cell lung cancer (NSCLC). In spite of potent efficacy, the conventional 1-day DP is regarded as having more toxicity as compared with GP. There is increasing interest in a biweekly split administration of DP to reduce its toxicity. Hypothesis was that first-line biweekly DP is as safe as GP in the elderly or poor performance status (PS) patients. METHODS: Chemotherapy-naïve patients with advanced NSCLC (IIIB/IV) who were elderly (65<) or PS (ECOG 2) were randomized to DP or GP arm by balancing for ECOG (0-1 vs...
March 24, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28325092/effectiveness-of-low-dose-oral-etoposide-treatment-in-patients-with-recurrent-and-platinum-resistant-epithelial-ovarian-cancer
#5
Yakup Bozkaya, Mutlu Doğan, Gökmen Umut Erdem, Gökhan Tulunay, Hikmet Uncu, Zafer Arık, Umut Demirci, Ozan Yazıcı, Nurullah Zengin
The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment...
March 21, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28314319/multicenter-phase-ii-clinical-trial-of-genexol-pm%C3%A2-with-gemcitabine-in-advanced-biliary-tract-cancer
#6
Jin Young Kim, Young Rok DO, Hong Suk Song, Yoon Young Cho, Hun Mo Ryoo, Sung Hwa Bae, Jong Gwang Kim, Yee Soo Chae, Byung Woog Kang, Jin Ho Baek, Min Kyoung Kim, Kyung Hee Lee, Keonuk Park
This multicenter phase II clinical trial was designed to evaluate the efficacy and safety of weekly Genexol-PM® and gemcitabine combination chemotherapy in patients with unresectable or metastatic biliary tract cancer. PATIENTS AND METHODS: Patients received 100 mg/m(2) Genexol-PM® and 1,000 mg/m(2) gemcitabine intravenously on days 1 and 8 every 21 days. RESULTS: Out of 39 patients, there were 10 partial responses (25.6%) and 18 with stable diseases (46.2%) were confirmed with median response duration 4...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28293715/a-phase-1-study-of-gemcitabine-nab-paclitaxel-s-1-gas-combination-neoadjuvant-chemotherapy-for-patients-with-locally-advanced-pancreatic-adenocarcinoma
#7
Naru Kondo, Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Naoya Nakagawa, Shinya Takahashi, Hiroki Ohge, Taijiro Sueda
PURPOSE: To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). METHODS: Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m(2), day 1), nab-paclitaxel (mg/m(2), day 1), and S-1 (mg/day, days 1-7) were 800/100/60-100 at level 1, and 1000/125/60-100 at level 2...
March 14, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28286977/comparison-of-treatment-patterns-resource-utilization-and-cost-of-care-in-patients-with-metastatic-pancreatic-cancer-treated-with-first-line-nab-paclitaxel-plus-gemcitabine-or-folfirinox
#8
George P Kim, Monika F Parisi, Manish B Patel, Corey L Pelletier, Kathy W Belk
BACKGROUND: We compared real-world treatment patterns, resource utilization, and cost of care for patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel + gemcitabine or FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin). METHODS: This was a retrospective study of inpatient and hospital-based outpatient data in the United States. Primary endpoints included median time to treatment discontinuation (TTD) and total cost of care per patient per month...
March 13, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28282277/role-of-stereotactic-body-radiotherapy-in-the-treatment-of-elderly-and-poor-performance-status-patients-with-pancreatic-cancer
#9
Lauren M Rosati, Joseph M Herman
Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy...
March 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28280326/lymph-cancer-chemotherapy-delivery-of-doxorubicin-gemcitabine-prodrug-and-vincristine-by-nanostructured-lipid-carriers
#10
Shuqin Ni, Lei Qiu, Guodong Zhang, Haiyan Zhou, Yong Han
PURPOSE: Radiation and chemotherapy are the most common course of treatment for B-cell lymphoma. Doxorubicin (DOX), gemcitabine (GEM), and vincristine (VCR) are the commonly used antilymphoma chemotherapeutic drugs. The aim of this study is to construct a novel drug delivery system for the combination delivery of the three drugs on lymphoma. MATERIALS AND METHODS: DOX-GEM prodrug was synthesized. Novel nanostructured lipid carriers (NLCs) containing DOX-GEM prodrug and VCR were prepared and used to treat B-cell lymphoma through in vivo treatment to a lymph cancer animal model...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28277162/modulation-of-chemotherapy-induced-cytotoxicity-in-sh-sy5y-neuroblastoma-cells-by-caffeine-and-chlorogenic-acid
#11
Susan Hall, Shailendra Anoopkumar-Dukie, Gary D Grant, Ben Desbrow, Richard Lai, Devinder Arora, Yinna Hong
Chemotherapy is an important treatment modality for malignancy but is limited by significant toxicity and it susceptibility to numerous drug interactions. While the interacting effects with medications are well known, there is limited evidence on the interaction with commonly consumed food and natural products. The aim of this study was to evaluate the bioactive constituents of coffee (caffeine and chlorogenic acid) on the cytotoxicity of doxorubicin, gemcitabine, and paclitaxel in vitro. Pretreatment with caffeine (100 nM and 10 μM) sensitized SH-SY5Y cells to doxorubicin-induced toxicity and increased apoptosis and sensitized PC3 cells to gemcitabine-induced toxicity...
March 6, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28270698/gut-microbiota-modulation-of-chemotherapy-efficacy-and-toxicity
#12
REVIEW
James L Alexander, Ian D Wilson, Julian Teare, Julian R Marchesi, Jeremy K Nicholson, James M Kinross
Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies...
March 8, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28259838/enzyme-responsive-peptide-dendrimer-gemcitabine-conjugate-as-a-controlled-release-drug-delivery-vehicle-with-enhanced-antitumor-efficacy
#13
Chengyuan Zhang, Dayi Pan, Jin Li, Jiani Hu, Ashika Bains, Nicholas Guys, Hongyan Zhu, Xiaohui Li, Kui Luo, Qiyong Gong, Zhongwei Guc
Stimuli-responsive peptide dendrimer-drug conjugates have presented significant potential for cancer therapy. To develop an effective nanoscale chemotherapeutic prodrug, we developed a novel enzyme-responsive PEGylated lysine peptide dendrimer-gemcitabine conjugate (Dendrimer-GEM) based nanoparticle via the highly efficient click reaction. Owing to the glycylphenylalanylleucylglycine tetra-peptide (GFLG) as an enzyme-cleavable linker to conjugate gemcitabine (GEM), the prepared nanoparticles were able to release drug significantly faster in the tumor cellular environments, which specifically contains secreted Cathepsin B, quantifiably more than 80% GEM was released with Cathepsin B compared to the condition without Cathepsin B at 24h...
March 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28258623/difference-in-toxicity-reporting-between-patients-and-clinicians-during-systemic-chemotherapy-in-patients-with-urothelial-carcinoma
#14
Ken Fukushi, Takuma Narita, Shingo Hatakeyama, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
OBJECTIVES: To compare toxicity reporting between patients and clinicians in the case of systemic chemotherapy for urothelial carcinoma. METHODS: Between June 2013 and March 2016, 100 urothelial carcinoma patients received two courses of chemotherapy of gemcitabine plus cisplatin or gemcitabine plus carboplatin, and they were prospectively enrolled in the present study. During chemotherapy, patients answered European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire C30 quality-of-life questionnaires, including four toxicity-related symptoms (appetite loss, nausea, constipation and diarrhea)...
March 4, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28253833/emerging-antibodies-for-the-treatment-of-pancreatic-cancer
#15
Kalliopi Andrikou, Chiara Peterle, Stefania Pipitone, Massimiliano Salati, Stefano Cascinu
Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment...
March 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28253828/emerging-protein-kinase-inhibitors-for-treating-pancreatic-cancer
#16
Junji Furuse, Fumio Nagashima
Pancreatic cancer, the incidence and mortality of which are increasing around the world, has the most dismal prognosis among the commonly encountered cancers. Systemic chemotherapy plays an important role in the treatment of patients with pancreatic cancer, and development of more effective chemotherapies is being sought. Areas covered: This review article provides a summary about protein kinase inhibitors that have been investigated for the treatment of pancreatic cancer, not only existing agents targeting RAS, EGFR, VEGFR, MEK, etc...
March 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28244416/longitudinal-changes-in-active-bone-marrow-for-cervical-cancer-patients-treated-with-concurrent-chemoradiation-therapy
#17
Sonal S Noticewala, Nan Li, Casey W Williamson, Carl K Hoh, Hanjie Shen, Michael T McHale, Cheryl C Saenz, John Einck, Steven Plaxe, Florin Vaida, Catheryn M Yashar, Loren K Mell
PURPOSE: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). METHODS AND MATERIALS: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m(2)) and 14 were treated with cisplatin (40 mg/m(2)) plus gemcitabine (50-125 mg/m(2)) (C/G)...
March 15, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28244408/tolerability-of-concurrent-chemoradiation-therapy-with-gemcitabine-gemx-with-and-without-prior-neoadjuvant-chemotherapy-in-muscle-invasive-bladder-cancer
#18
Catherine Thompson, Nuradh Joseph, Benjamin Sanderson, John Logue, James Wylie, Tony Elliott, Jeanette Lyons, Carmel Anandadas, Ananya Choudhury
PURPOSE: The aim of this study is to assess the tolerability of concurrent chemoradiation therapy with gemcitabine (GemX) in muscle invasive bladder cancer following neoadjuvant chemotherapy (neoGemX) by use of patient- and provider-reported outcomes. METHODS AND MATERIALS: Seventy-eight patients were treated with GemX. Thirty-eight received prior neoadjuvant chemotherapy (NAC). Patients were prospectively assessed during treatment and at 6 weeks and 12 months after treatment completion...
March 15, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28230029/clinical-efficacy-and-safety-of-gemcitabine-plus-nedaplatin-in-the-treatment-of-advanced-nasopharyngeal-carcinoma
#19
Yan Hu, Jiang Tao Fu, Dongmei Shi, Biao Feng, Zhichao Shi
OBJECTIVE: The purpose was to explore the clinical effects and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma. MATERIALS AND METHODS: From March 2014 to August 2015, we recruited 63 advanced nasopharyngeal carcinoma patients in our hospital. Moreover, the 62 cases were randomly divided into control group (n = 31) and treatment group (n = 32). Patients in the control groups were treated with 5-fluorouracil 500 mg/m 2 + 500 ml 0...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28225482/a-case-report-of-posterior-reversible-encephalopathy-syndrome-in-a-patient-receiving-gemcitabine-and-cisplatin
#20
Hannah Cherniawsky, Neesha Merchant, Micheal Sawyer, Maria Ho
RATIONALE: Posterior reversible encephalopathy syndrome (PRES) is a subacute syndrome causing characteristic neurologic and radiologic findings. PRES is predominantly caused by malignant hypertension though it has been associated with immunosuppressive treatments such as chemotherapy. PATIENT CONCERNS: We describe a case of a 58 year old female who developed fluctuant level of consciousness, agitation. DIAGNOSIS: MRI findings were in keeping with posterior reversible encephalopathy syndrome following cycle 6 of palliative gemcitabine and cisplatin therapy for metastatic cholangiocarcinoma...
February 2017: Medicine (Baltimore)
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