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Viviana Izzo, Bruno Charlier, Elena Bloise, Marine Pingeon, Marianna Romano, Antonietta Finelli, Alfonso Vietri, Valeria Conti, Valentina Manzo, Maria Alfieri, Amelia Filippelli, Fabrizio Dal Piaz
Exposure of healthcare workers to anticancer drugs requires the combined action of environmental and biological monitoring to assess the effective level of exposure to these chemicals, to improve awareness and to avoid adverse health effects on this category of workers. Cancer chemotherapeutic drugs show different mechanisms of action due to diverse chemical structures; consequently, they differ in hydrophobicity, pharmacokinetics and pharmacodynamics. Therefore, the appearance, accumulation and elimination of each of these molecules in body fluids and tissues might be extremely variable; this prompts the need for a rapid and versatile analytical protocol for the biological monitoring of possible exposure of workers involved in the manipulation, administration and disposal of cancer chemotherapeutic drugs...
March 13, 2018: Journal of Pharmaceutical and Biomedical Analysis
Matthieu Germain, Marie-Edith Meyre, Laurence Poul, Marion Paolini, Céline Berjaud, Francis Mpambani, Maxime Bergere, Laurent Levy, Agnès Pottier
Many therapeutic agents offer a low useful dose (dose responsible for efficacy)/useless dose (dose eliminated or responsible for toxicity) ratio, mainly due to the fact that therapeutic agents must ensure in one single object all the functions required to deliver the treatment, which leads to compromises in their physico-chemical design. Here we introduce the concept of priming the body to receive the treatment by uncorrelating these functions into two distinct objects sequentially administered: a nanoprimer occupying transiently the main pathway responsible for therapeutic agent limited benefit/risk ratio followed by the therapeutic agent...
March 19, 2018: Scientific Reports
Timothy J Price
No abstract text is available yet for this article.
March 16, 2018: Lancet Oncology
Rui-Hua Xu, Kei Muro, Satoshi Morita, Satoru Iwasa, Sae Won Han, Wei Wang, Masahito Kotaka, Masato Nakamura, Joong Bae Ahn, Yan-Hong Deng, Takeshi Kato, Sang-Hee Cho, Yi Ba, Hiroshi Matsuoka, Keun-Wook Lee, Tao Zhang, Yasuhide Yamada, Junichi Sakamoto, Young Suk Park, Tae Won Kim
BACKGROUND: Studies of a modified XELIRI (mXELIRI; capecitabine plus irinotecan) regimen suggest promising efficacy and tolerability profiles in the first-line and second-line settings. Therefore, we aimed to compare the efficacy and safety of the mXELIRI regimen with that of standard FOLFIRI (leucovorin, fluorouracil, and irinotecan), with or without bevacizumab in both regimens, as a second-line therapy for metastatic colorectal cancer. METHODS: We did a multicentre, open-label, randomised, non-inferiority, phase 3 trial...
March 16, 2018: Lancet Oncology
Hongyang Lu, Bo Chen, Jing Qin, Fajun Xie, Na Han, Zhiyu Huang
The present study describes the case of a 48-year-old man who was diagnosed with lung adenocarcinoma with an epidermal growth factor receptor (EGFR) 21 L858R mutation. The patient received surgery and adjuvant chemotherapy. When multiple lung metastases appeared, icotinib was administered. Following resistance to icotinib, biopsy by endobroncheal ultrasonography for a right lung hilar lymph node revealed transformation to a neuroendocrine morphology. Neuron-specific enolase (NSE) levels were elevated, accompanied with disease progression following transformation to the neuroendocrine morphology...
April 2018: Oncology Letters
Maha S Al-Keilani, Dua H Alsmadi, Ruba S Darweesh, Karem H Alzoubi
Background: Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus. Objectives: To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53...
2018: Clinical Pharmacology: Advances and Applications
Roberto Petrioli, Martina Chirra, Luciana Messuti, Anna Ida Fiaschi, Vinno Savelli, Ignazio Martellucci, Edoardo Francini
BACKGROUND: In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC...
February 21, 2018: Clinical Colorectal Cancer
Karen Kinsley, Wendy Pritchett
Recent approaches in treating pancreatic adenocarcinoma, an aggressive disease with limited survival, include the use of liposomal irinotecan as an option when first-line therapy has failed. Liposomal irinotecan has been approved in combination with 5-fluorouracil and leucovorin for patients with metastatic pancreatic cancer. Liposomal irinotecan is a newer therapy requiring oncology nurses to obtain knowledge and skills for proper administrating, monitoring of hypersensitivity reactions during infusion, managing side effects, and providing patient education...
April 1, 2018: Clinical Journal of Oncology Nursing
Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Brianne R O'Leary, Frederick K Houwen, Chase L Johnson, Bryan G Allen, James J Mezhir, Daniel J Berg, Joseph J Cullen, Douglas R Spitz
Gastric adenocarcinoma most often presents at an advanced stage and overall five-year survival of ∼30%. Pharmacological ascorbate (high-dose IV ascorbate) has been proposed as a promising nontoxic adjuvant to standard radio-chemotherapies in several cancer types. In the current study, pharmacological ascorbate (0.5-2 m M) caused a dose-dependent decrease (70-85% at 2 m M) in clonogenic survival of gastric adenocarcinoma cells (AGS and MNK-45), but was relatively nontoxic to a small intestinal epithelial nonimmortalized human cell isolate (FHs 74 Int)...
March 16, 2018: Radiation Research
Michael K Krapf, Jennifer Gallus, Sahel Vahdati, Michael Wiese
Multidrug resistance occurring during cancer chemotherapy is a major obstacle for effectiveness and response to therapy and is often caused by ATP-binding cassette (ABC) efflux transporters. Belonging to the family of ABC transporters, breast cancer resistance protein is getting more and more in the spotlight of research. As a strategy to overcome multidrug resistance, inhibitors of ABC transporters were synthesized, which could be applied in combination with cytostatic drugs. For this purpose, 2,4-disubstituted pyridopyrimidine derivatives were synthesized...
March 16, 2018: Journal of Medicinal Chemistry
Midori Tanaka, Hidenobu Ishii, Hayato Moribuchi, Yoshiko Naito, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Koichi Azuma, Kazuhiko Yamada, Tomoaki Hoshino
Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...
March 15, 2018: Investigational New Drugs
Shuko Hakata, Jun Terashima, Yu Shimoyama, Kouji Okada, Shiho Fujioka, Erika Ito, Wataru Habano, Shogo Ozawa
Irinotecan (CPT-11) is a key therapeutic drug used in the treatment of colorectal cancer, although acquired or constitutive resistance to CPT-11 (and its activated metabolite SN-38) can lead to tumor progression. Since the acquisition of drug resistance can result from DNA hypermethylation, the antitumor activity of CPT-11 and SN-38 was assessed in combination with a known DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, also known as decitabine (DAC). DAC potentiated the antitumor activity of CPT-11 additively, and that of SN-38 synergistically, as measured by colony formation in the human colorectal cancer HCT116 cell line...
April 2018: Oncology Letters
Michael Nagel, Julia Schulz, Annett Maderer, Katrin Goepfert, Nadine Gehrke, Thomas Thomaidis, Peter C Thuss-Patience, Salah E Al-Batran, Susanna Hegewisch-Becker, Peter Grimminger, Peter Robert Galle, Markus Möhler, Jörn Markus Schattenberg
BACKGROUND: Gastric cancer is common malignancy and exhibits a poor prognosis. At the time of diagnosis, the majority of patients present with metastatic disease which precludes curative treatment. Non-invasive biomarkers which discriminate early from advanced stages or predict the response to treatment are urgently required. This study explored the cytokeratin-18 fragment M30 and full-length cytokeratin-18 M65 in predicting treatment response and survival in a randomized, placebo-controlled trial of advanced gastric cancer...
March 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
E Palmerini, R L Jones, E Setola, P Picci, E Marchesi, R Luksch, G Grignani, M Cesari, A Longhi, M E Abate, A Paioli, Z Szucs, L D'ambrosio, K Scotlandi, F Fagioli, S Asaftei, S Ferrari
BACKGROUND: Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. METHODS: Patients receiving TEM 100 mg/m2 /day oral, and IRI 40 mg/m2 /day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed...
March 13, 2018: Acta Oncologica
Chiara Cremolini, Massimo Milione, Federica Marmorino, Federica Morano, Gemma Zucchelli, Alessia Mennitto, Michele Prisciandaro, Sara Lonardi, Alessio Pellegrinelli, Daniele Rossini, Francesca Bergamo, Giuseppe Aprile, Lucio Urbani, Luca Morelli, Marta Schirripa, Giovanni Gerardo Cardellino, Matteo Fassan, Gabriella Fontanini, Filippo de Braud, Vincenzo Mazzaferro, Alfredo Falcone, Filippo Pietrantonio
BACKGROUND: Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs...
March 13, 2018: British Journal of Cancer
Eiji Oki, Takeshi Kato, Hideaki Bando, Takayuki Yoshino, Kei Muro, Hiroya Taniguchi, Yoshinori Kagawa, Kentaro Yamazaki, Tatsuro Yamaguchi, Akihito Tsuji, Shigeyoshi Iwamoto, Goro Nakayama, Yasunori Emi, Tetsuo Touyama, Masato Nakamura, Masahito Kotaka, Hideki Sakisaka, Takeharu Yamanaka, Akiyoshi Kanazawa
BACKGROUND: FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. PATIENTS AND METHODS: This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab...
February 9, 2018: Clinical Colorectal Cancer
Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo
Purpose: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). Materials and Methods: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8 + cisplatin 70 mg/m2 intravenously on day1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred...
March 12, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Hiroshi Ishii, Natsumi Yamashita, Makoto Ueno, Shinichi Ohkawa, Akiko M Saito, Mitsugu Sekimoto
Introduction: In Japan, the age of patients with pancreatic cancer has increased. Combination chemotherapies such as 5-fluorouracil/leucovorin, oxaliplatin and irinotecan therapy and gemcitabine hydrochloride (GEM) +nab paclitaxel therapy have been developed as the standard treatments for young patients with advanced recurrent pancreatic cancer. However, both therapies produce toxicity and their administration is limited by the patients' age or performance status. The efficacy and safety data obtained in the GEST study-a large-scale randomised controlled study conducted in patients with pancreatic cancer in Japan-suggested that GEM +S-1 (GS) combination therapy is a promising candidate for those aged between 75 and 80 years...
2018: BMJ Open Gastroenterology
Jordan Berlin, Ramesh K Ramanathan, John H Strickler, Deepa S Subramaniam, John Marshall, Yoon-Koo Kang, Robert Hetman, Matthew W Dudley, Jiewei Zeng, Caroline Nickner, Hao Xiong, Philip Komarnitsky, Stacie Peacock Shepherd, Herbert Hurwitz, Heinz-Josef Lenz
BACKGROUND: Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours. METHODS: Patients received veliparib (10-270 mg BID, days 1-5, 15-19) and FOLFIRI (days 1-3, 15-17) in three regimens containing 5-fluorouracil 2,400 mg/m2 : irinotecan 150 mg/m2 and folinic acid 400 mg/m2 (part 1); irinotecan 180 mg/m2 , folinic acid 400 mg/m2 , and 5-fluorouracil 400 mg/m2 bolus (part 2), or irinotecan 180 mg/m2 (part 3)...
March 12, 2018: British Journal of Cancer
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