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Gemcitabine toxicity

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https://www.readbyqxmd.com/read/29338080/phase-1-trial-evaluating-cisplatin-gemcitabine-and-veliparib-in-2-patient-cohorts-germline-brca-mutation-carriers-and-wild-type-brca-pancreatic-ductal-adenocarcinoma
#1
Eileen M O'Reilly, Jonathan W Lee, Maeve A Lowery, Marinela Capanu, Zsofia K Stadler, Malcolm J Moore, Neesha Dhani, Hedy L Kindler, Hayley Estrella, Hannah Maynard, Talia Golan, Amiel Segal, Erin E Salo-Mullen, Kenneth H Yu, Andrew S Epstein, Michal Segal, Robin Brenner, Richard K Do, Alice P Chen, Laura H Tang, David P Kelsen
BACKGROUND: A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in Solid Tumors, version 1...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29332329/modified-3-week-schedule-of-gemcitabine-plus-cisplatin-for-non-small-cell-lung-cancer-treatment
#2
Antonello Veccia, Viviana Murgia, Mariachiara Dipasquale, Orazio Caffo
PURPOSE: Gemcitabine-cisplatin combination is one of the most used schedules for non small cell lung cancer (NSCLC). Aiming to enhance dose intensity and reduce toxicity, the original 4-week schedule was modified or transformed into a 3-week schedule. The purpose of this study was to report the efficacy and tolerability of a modified 3-week regimen of gemcitabine-cisplatin. METHODS: Our patients were treated with gemcitabine (1000 mg7sol;m2) on days 1, 8 and cisplatin on day 8 (75-100 mg/m2)...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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
#3
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/29301833/establishing-a-preclinical-multidisciplinary-board-for-brain-tumors
#4
Birgit Nimmervoll, Nidal Boulos, Brandon M Bianski, Jason Dapper, Michael DeCuypere, Anang A Shelat, Sabrina Terranova, Hope Elizabeth Terhune, Amar Gajjar, Yogesh T Patel, Burgess B Freeman, Arzu Onar-Thomas, Clinton F Stewart, Martine F Roussel, R Kiplin Guy, Thomas E Merchant, Christopher Calabrese, Karen D Wright, Richard J Gilbertson
PURPOSE: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies.  It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors.  Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials.  Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC)...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#5
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29299370/safety-of-selective-internal-radiation-therapy-sirt-with-yttrium-90-microspheres-combined-with-systemic-anticancer-agents-expert-consensus
#6
REVIEW
Andrew Kennedy, Daniel B Brown, Jonas Feilchenfeldt, John Marshall, Harpreet Wasan, Marwan Fakih, Peter Gibbs, Alexander Knuth, Bruno Sangro, Michael C Soulen, Gianfranco Pittari, Ricky A Sharma
Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible patients have usually been exposed to a variety of systemic anticancer therapies, including cytotoxic agents, targeted biologics, immunotherapy and peptide receptor radionuclide therapy (PRRT). All these treatments have potential interactions with SIRT; however, robust evidence on the safety of these potential combinations is lacking...
December 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29286192/combination-of-pegylated-liposomal-doxorubicin-plus-gemcitabine-in-heavily-pretreated-metastatic-breast-cancer-patients-long-term-results-from-a-single-institution-experience
#7
Patricia Martin-Romano, Iosune Baraibar, Jaime Espinós, Jairo Legaspi, Jose M López-Picazo, Jose Manuel Aramendía, Oscar A Fernández, Marta Santisteban
The combination of Pegylated Liposomal Doxorubicin (PLD) plus Gemcitabine (GEM) has been previously investigated in the treatment of metastatic breast cancer (MBC). PLD is a doxorubicin formulation with prolonged circulation time and better tissue distribution. GEM is a nucleoside analog with nonoverlapping toxicity compared to PLD. The aim of our study was to assess efficacy, toxicity, and long-term outcome of this combination. Patients with heavily treated MBC were retrospectively analyzed. Chemotherapy consisted of PLD 25 mg/m2 and GEM 800 mg/m2 day 1, on a three-week schedule...
December 29, 2017: Breast Journal
https://www.readbyqxmd.com/read/29285384/the-combination-of-paclitaxel-and-carboplatin-as-second-line-chemotherapy-can-be-a-preferred-regimen-for-patients-with-urothelial-carcinoma-after-the-failure-of-gemcitabine-and-cisplatin-chemotherapy
#8
Nobuki Furubayashi, Takahito Negishi, Takuya Yamashita, Shuhei Kusano, Kenichi Taguchi, Mototsugu Shimokawa, Motonobu Nakamura
There is no established standard second-line chemotherapy after the failure of the first-line cisplatin-based chemotherapy for patients with advanced or metastatic urothelial carcinoma. With regards to second-line chemotherapy, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) was used from July 2009 onwards, and paclitaxel and carboplatin (TC) was introduced in April 2014 at the National Kyushu Cancer Center. The present study aimed to assess the prognostic factors for overall survival (OS) in second-line treatment that included best supportive care (BSC), and the tolerability and efficacy of TC chemotherapy...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29285038/a-multicenter-phase-ii-trial-of-neoadjuvant-chemotherapy-with-docetaxel-and-gemcitabine-in-locally-advanced-breast-cancer
#9
Ye Won Jeon, Tae Hyun Kim, Hyun Jo Youn, Sehwan Han, Yongsik Jung, Geumhee Gwak, Young Sam Park, Jeong Soo Kim, Young Jin Suh
Purpose: The current multicenter phase II study was conducted to evaluate the efficacy and safety of the combination of docetaxel and gemcitabine as neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. Methods: A total of 98 patients with stage II-III breast cancer were enrolled. The primary endpoint was pathological complete response (pCR) rate of invasive cancer after the completion of the fourth cycle of NAC. The secondary endpoints included response rate (RR), rate of breast-conserving surgery, toxicity, and disease-free survival (DFS)...
December 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/29284644/cox-2-seh-dual-inhibitor-ptupb-potentiates-the-anti-tumor-efficacy-of-cisplatin
#10
Fuli Wang, Hongyong Zhang, Ai-Hong Ma, Weimin Yu, Maike Zimmermann, Jun Yang, Sung Hee Hwang, Daniel Zhu, Tzu-Yin Lin, Michael Malfatti, Kenneth W Turteltaub, Paul T Henderson, Susan Airhart, Bruce D Hammock, Jianlin Yuan, Ralph W de Vere White, Chong-Xian Pan
Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in anti-tumor activity, and has organ protective effects. The goal of this study was to determine the anti-tumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC or combinations thereof...
December 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29277822/bevacizumab-added-to-moderate-dose-chemotherapy-for-refractory-uterine-cancer
#11
Howard W Bruckner, Daniel Gurell, Azriel Hirschfeld
BACKGROUND/AIM: Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs. PATIENTS AND METHODS: Eligible patients (n=9) had high-grade endometrial tumors and had failed standard chemotherapy...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29273076/highly-conformal-combined-radiotherapy-with-cisplatin-and-gemcitabine-for-treatment-of-loco-regionally-advanced-cervical-cancer-a-retrospective-study
#12
Nikola Cihoric, Alexandros Tsikkinis, Eugenia Vlaskou Badra, Markus Glatzer, Urban Novak, Amina Scherz, Mohamed Shelan, Ivan Soldatovic, Chittazhathu Kurian Kuruvilla Yojena, Daniel M Aebersold, Kristina Lössl
BACKGROUND: Cisplatin and gemcitabine combined with conventional radiation therapy in the treatment of cervical cancer patients results in a favorable outcome but with excess toxicity. The purpose of this study was to evaluate the toxicity profile of dual chemotherapy and highly conformal external beam radiotherapy with image guided adaptive brachytherapy. METHODS: Seventeen patients with cervical carcinoma FIGO stage IB2-IIIB were treated with curative intent between 2011 and 2015...
December 22, 2017: Radiation Oncology
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
#13
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/29235457/serum-metabolic-profile-alteration-reveals-response-to-platinum-based-combination-chemotherapy-for-lung-cancer-sensitive-patients-distinguished-from-insensitive-ones
#14
Shan Xu, Yanping Zhou, Hui Geng, Dandan Song, Jing Tang, Xianmin Zhu, Di Yu, Sheng Hu, Yanfang Cui
Most lung cancers are diagnosed at fairly advanced stages due to limited clinical symptoms. Platinum-based chemotherapy, either as single regimen or in combination with radiation, is one of the major recommendations for the patients. Earlier evaluation of the effectiveness of the chemotherapies is critical for developing better treatment plan given the toxicity of the chemotherapeutic reagents. Drug efficacy could be reflected in the systemic metabolism characteristics though knowledge about which remains scarce...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233971/implication-of-4e-bp1-protein-dephosphorylation-and-accumulation-in-pancreatic-cancer-cell-death-induced-by-combined-gemcitabine-and-trail
#15
Androulla Elia, Ricky Henry-Grant, Charlotte Adiseshiah, Catherine Marboeuf, Rebecca J Buckley, Michael J Clemens, Satvinder Mudan, Stéphane Pyronnet
Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1...
December 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29228572/gemcitabine-cisplatin-induction-chemotherapy-before-concurrent-chemotherapy-and-intensity-modulated-radiotherapy-improves-outcomes-for-locoregionally-advanced-nasopharyngeal-carcinoma
#16
Wang Fangzheng, Sun Quanquan, Jiang Chuner, Wang Lei, Yan Fengqin, Ye Zhimin, Liu Tongxin, Xu Min, Wu Peng, Jiang Haitao, Rihito Aizawa, Masoto Sakamoto, Wang Yuezhen, Fu Zhenfu
Addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CC) is an encouraging first-line treatment strategy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We evaluated the clinical efficacy and toxicity of addition of gemcitabine plus cisplatin (GP) IC to intensity-modulated radiotherapy (IMRT) and CC for patients with locoregionally advanced NPC. At a median follow-up duration of 48 months (10-59 months), 4-year local relapse-free survival (LRFS) was 86.9%, regional relapse-free survival (RRFS) was 90...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215048/high-dose-parenteral-ascorbate-inhibited-pancreatic-cancer-growth-and-metastasis-mechanisms-and-a-phase-i-iia-study
#17
Kishore Polireddy, Ruochen Dong, Gregory Reed, Jun Yu, Ping Chen, Stephen Williamson, Pierre-Christian Violet, Ziyan Pessetto, Andrew K Godwin, Fang Fan, Mark Levine, Jeanne A Drisko, Qi Chen
Pancreatic cancer is among the most lethal cancers with poorly tolerated treatments. There is increasing interest in using high-dose intravenous ascorbate (IVC) in treating this disease partially because of its low toxicity. IVC bypasses bioavailability barriers of oral ingestion, provides pharmacological concentrations in tissues, and exhibits selective cytotoxic effects in cancer cells through peroxide formation. Here, we further revealed its anti-pancreatic cancer mechanisms and conducted a phase I/IIa study to investigate pharmacokinetic interaction between IVC and gemcitabine...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212973/-refractory-cd20-positive-peripheral-t-cell-lymphoma-showing-loss-of-cd20-expression-after-rituximab-therapy-and-gain-of-cd20-expression-after-administration-of-vorinostat-and-gemcitabine
#18
Kazuaki Teshima, Hideaki Ohyagi, Masaaki Kume, Satsuki Takahashi, Masahiro Saito, Naoto Takahashi
A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29203108/effect-of-taurine-on-immune-function-in-mice-with-t-cell-lymphoma-during-chemotherapy
#19
Jin-Feng Dong, Xiao-Qiang Zheng, Hong-Bing Rui
OBJECTIVE: To observe the effect of taurine on immune function in mice with T-cell lymphoma during chemotherapy. METHODS: A total of 40 C57BL/6 mice were selected and randomly divided into 4 groups, namely model group, chemotherapy group, taurine group and chemotherapy + taurine group, each containing 10 mice. Hypodermic injection was adopted to inoculate EL-4 cells in order to establish model of T-cell lymphoma. When the tumor achieved the size of 1 cm3, intervention treatments were given to the groups respectively...
November 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29199683/gemcitabine-and-carboplatin-in-metastatic-nonsmall-cell-lung-cancer-experience-from-a-tertiary-cancer-center-in-south-india
#20
T Devika, B Dubashi, D G Shewade, S Kayal, Rcs Kumar
BACKGROUND: Gemcitabine and carboplatin combination is widely used as one of the first-line chemotherapeutic regimens in patients with metastatic nonsmall cell lung cancer patients. METHODOLOGY: A total of 112 patients with metastatic disease were recruited. They were on standard 21-day gemcitabine 1.2 g/m2 and carboplatin AUC 5 dosing schedule. Each patient received at least four cycles and a maximum of 6 cycles of treatment. The patients were followed up, and the demographic, efficacy and toxicity profiles were analyzed...
January 2017: Indian Journal of Cancer
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