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treatment escalation

Si Yeol Song, Kyu-Pyo Kim, Seong-Yun Jeong, Jin Park, Jaesook Park, Joohee Jung, Hye Kyung Chung, Sa-Won Lee, Min Hyo Seo, Jung-Shin Lee, Kyung Hae Jung, Eun Kyung Choi
We assessed the efficacy of the polymeric nanoparticle containing docetaxel (PNP-DTX) in preclinical mouse models and determined the maximum tolerated dose (MTD) through clinical study. Subcutaneous and orthotopic mouse models were dedicated. Tumor growth delay in orthotopic model and quantification of in vivo imaging in orthotopic model were evaluated. Phase I clinical study was a single-center, prospective, open-label trial in advanced solid tumors. PNP-DTX was injected intravenously and the starting dose was 20 mg/m2 escalated to 35 mg/m2, 45 mg/m2, 60 mg/m2 and 75 mg/m2...
October 14, 2016: Oncotarget
Michelle Hook, Sarah Woller, Eric Bancroft, Miriam Aceves, Mary Katherine Funk, John Hartman, Sandra M Garraway
Opioids and NSAIDs are commonly used to manage pain in the early phase of spinal cord injury (SCI). Despite its analgesic efficacy, however, our studies suggest that intrathecal (i.t.) morphine undermines locomotor recovery and increases lesion size in a rodent model of SCI. Similarly, intravenous (i.v.) morphine attenuates locomotor recovery. The current study explores whether i.v. morphine also increases lesion size after a spinal contusion (T12) injury, and quantifies the cell types that are affected by early opioid administration...
October 20, 2016: Journal of Neurotrauma
Matthew D Hall, Timothy E Schultheiss, David D Smith, Marwan G Fakih, Jeffrey Y C Wong, Yi-Jen Chen
BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision...
October 20, 2016: Acta Oncologica
Amita Trehan, Deepak Bansal, Neelam Varma, Ajay Vora
BACKGROUND: The outcome of malignancies in low- and middle-income countries (LMICs) is hampered owing to numerous factors. Current protocols are complex, demanding supportive care, often not optimally available. We de-escalated the UKALL 2003 protocol to improve the outcome of acute lymphoblastic leukemia (ALL) at our center. METHODS: In 2007-2009, children were treated as per the UKALL 2003 protocol (protocol 1). In 2010 and 2011, a modified version of the UKALL 2003 (protocol 2) was followed...
October 20, 2016: Pediatric Blood & Cancer
Firas El Chaer, Dimpy P Shah, Roy F Chemaly
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy...
October 19, 2016: Blood
Tatsuya Kondo, Rieko Goto, Kaoru Ono, Sayaka Kitano, Mary Ann Suico, Miki Sato, Motoyuki Igata, Junji Kawashima, Hiroyuki Motoshima, Takeshi Matsumura, Hirofumi Kai, Eiichi Araki
Activation of heat shock response (HSR) improves accumulated visceral adiposity and metabolic abnormalities in type 2 diabetes. To identify the optimal intervention strategy of the activation of the HSR provided by mild electrical stimulation (MES) with heat shock (HS) in type 2 diabetes. This study was a prospective, frequency-escalating, randomized, open-label, triple-arm trial in Japan. A total of 60 obese type 2 diabetes patients were randomized into three groups receiving two, four, or seven treatments per week for 12 weeks...
October 19, 2016: Scientific Reports
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Neil H Segal, Theodore F Logan, F Stephen Hodi, David F McDermott, Ignacio Melero, Omid Hamid, Henrik Schmidt, Caroline Robert, Vanna Chiarion-Sileni, Paolo A Ascierto, Michele Maio, Walter J Urba, Tara C Gangadhar, Satyendra Suryawanshi, Jaclyn Neely, Maria Jure-Kunkel, Suba Krishnan, Holbrook E Kohrt, Mario Sznol, Ronald Levy
PURPOSE: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma. PATIENTS AND METHODS: Three hundred and forty-six patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose-escalation, monotherapy studies...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Perparim Limani, Michael Linecker, Philipp Kron, Panagiotis Samaras, Bernhard Pestalozzi, Roger Stupp, Alexander Jetter, Philipp Dutkowski, Beat Müllhaupt, Andrea Schlegel, Claude Nicolau, Jean-Marie Lehn, Henrik Petrowsky, Bostjan Humar, Rolf Graf, Pierre-Alain Clavien
BACKGROUND: Solid tumors, such as hepato-pancreato-biliary cancer, develop tumor hypoxia with tumor growth. Despite advances in surgery, a majority of these patients are in an unresectable condition. At this stage standard cytotoxic chemotherapy regimens are applied with limited success. Novel biological treatment options based on an antiangiogenic mechanism of action neglect other hypoxia mediated mechanisms (e.g. epithelial-mesenchymal transition, Warburg effect, and immunological response) leading to an increased invasiveness with a poor outcome...
October 19, 2016: BMC Cancer
Jacqueline R Kelly, Zain A Husain, Barbara Burtness
Increasingly, squamous cell carcinoma of the oropharynx (OPSCC) is attributable to transformation resulting from high-risk human papillomavirus (HPV) infection. Such cancers are significantly more responsive to treatment than traditional tobacco- and alcohol-associated squamous cell cancers of the head and neck. Conventional management with definitive chemoradiation, surgery and adjuvant radiation, or radiation given with altered fractionation schemes, while effective, incurs long-term morbidity that escalates with treatment intensity and significantly impairs quality of life...
October 15, 2016: European Journal of Cancer
Sameer Bakhshi, Sainath Bhethanabhotla, Rakesh Kumar, Krishankant Agarwal, Punit Sharma, Sanjay Thulkar, Arun Malhotra, Deepa Dhawan, Sreenivas Vishnubhatla
BACKGROUND: Data about significance of (18)F-FDG positron emission tomography (PET) at interim assessment and end of treatment in pediatric Hodgkin lymphoma (HL) are limited. METHODS: Patients (≤18 years) with HL were prospectively evaluated with contrast-enhanced computed tomography (CECT) and PET combined with low-dose CT(PET-CT) at baseline, post 2 cycles of chemotherapy and post completion of treatment. Revised international working group criteria (RIW) and Deauville (DA) five point-scale for response assessment by PET-CT were used...
October 6, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Nazanin Ebrahimiadib, Bobeck S Modjtahedi, Samaneh Davoudi, C Stephen Foster
PURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3...
October 18, 2016: Ocular Immunology and Inflammation
Julie M Waldfogel, Suzanne Nesbit, Steven P Cohen, Sydney M Dy
Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA)...
October 18, 2016: Journal of Pain & Palliative Care Pharmacotherapy
Francesco Cappuccio
The evidence. Salt (i.e. sodium chloride) is causally related to blood pressure (BP). The higher the salt intake, the higher the BP, an effect seen since birth. A small and sustained reduction in salt intake causes a fall in BP. The evidence from controlled studies, small and large, short and long, all agree on the following: (1) salt intake is one of the major determinants of BP in populations and individuals; (2) a reduction in salt intake causes a dose-dependent reduction in BP - the lower the salt the lower the BP; (3) the effect is seen in both sexes, in people of all ages and ethnic groups, and with all starting BPs...
September 2016: Journal of Hypertension
A Venkatraman, A Khawaja, A K Bag, M Mirza, J P Szaflarski, S Pati
Lateralized Periodic Discharges (LPDs) are commonly seen on EEG in critically-ill patients. They are often associated with seizures, but some patients may have them without seizures. Therefore, they are considered to lie in the ictal-interictal continuum. When ictal, they require multiple antiepileptic drugs to treat effectively, which can expose the patient to iatrogenic complications. Therefore, optimal management is controversial. We present here two cases where perfusion-weighted Magnetic Resonance Imaging (pMRI) was useful in distinguishing ictal from interictal LPDs...
October 5, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Rugmani Padmanabhan Iyer, Lisandra E de Castro Brás, Nicolle L Patterson, Manishabrata Bhowmick, Elizabeth R Flynn, Majdouline Asher, Presley L Cannon, Kristine Y Deleon-Pennell, Gregg B Fields, Merry L Lindsey
Matrix metalloproteinase-9 (MMP-9) is robustly elevated in the first week post-myocardial infarction (MI). Targeted deletion of the MMP-9 gene attenuates cardiac remodeling post-MI by reducing macrophage infiltration and collagen accumulation through increased apoptosis and reduced inflammation. In this study, we used a translational experimental design to determine whether selective MMP-9 inhibition early post-MI would be an effective therapeutic strategy in mice. We enrolled male C57BL/6J mice (3-6months old, n=116) for this study...
October 13, 2016: Journal of Molecular and Cellular Cardiology
Rebecca B Goody, Helen MacKay, Bethany Pitcher, Amit Oza, Lillian L Siu, John Kim, Rebecca K S Wong, Eric Chen, Carol Swallow, Jennifer Knox, Zahra Kassam, Bernard Cummings, Ron Feld, David Hedley, Geoffrey Liu, Monika K Krzyzanowska, Robert Dinniwell, Anthony M Brade, Laura A Dawson, Melania Pintilie, Jolie Ringash
PURPOSE: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma...
August 31, 2016: International Journal of Radiation Oncology, Biology, Physics
Jaroslaw T Hepel, Kara Lynne Leonard, Howard Safran, Thomas Ng, Angela Taber, Humera Khurshid, Ariel Birnbaum, David E Wazer, Thomas DiPetrillo
PURPOSE: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). METHODS AND MATERIALS: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively)...
August 31, 2016: International Journal of Radiation Oncology, Biology, Physics
David K Packham, Ian R Fraser, Peter G Kerr, Karen R Segal
BACKGROUND: Diabetic nephropathy is the most common cause of end stage renal failure. We assessed the safety, tolerability, and explored therapeutic effects of adult allogeneic bone-marrow derived mesenchymal precursor cells (MPC) in patients with moderate to severe diabetic nephropathy. METHODS: Multicenter, randomized, double-blind, dose-escalating, sequential, placebo-controlled trial assessing a single intravenous (IV) infusion of allogeneic MPC (United States adopted name: rexlemestrocel-L) 150×10(6) (n=10), 300×10(6) (n=10) or placebo (n=10) in adults with diabetic nephropathy with an estimated glomerular filtration rate (eGFR) 20-50ml/min/1...
September 17, 2016: EBioMedicine
C Gzell, M Back, H Wheeler, D Bailey, M Foote
The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered...
October 13, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
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