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Solomon B.J.,Peter MacCallum Cancer Center | Mok T.,Chinese University of Hong Kong | Kim D.-W.,Seoul National University | Wu Y.-L.,Guangdong Lung Cancer Institute | And 11 more authors.
New England Journal of Medicine | Year: 2014

Background The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown.Methods We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of bodysurface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression- free survival as assessed by independent radiologic review.Results Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P = 0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life.Conclusions Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.). © 2014 Massachusetts Medical Society.


Marcet J.E.,University of South Florida | Nfonsam V.N.,Arizona Cancer Center | Larach S.,Florida Hospital Cancer Institute
Journal of Pain Research | Year: 2013

Background: Opioid analgesics are effective for postsurgical pain but are associated with opioid-related adverse events, creating a significant clinical and economic burden. Gastrointestinal surgery patients are at high risk for opioid-related adverse events. We conducted a study to assess the impact of an opioid-sparing multimodal analgesia regimen with liposome bupivacaine, compared with the standard of care (intravenous [IV] opioid-based, patient-controlled analgesia [PCA]) on postsurgical opioid use and health economic outcomes in patients undergoing ileostomy reversal. Methods: In this open-label, multicenter study, sequential cohorts of patients undergoing ileostomy reversal received IV opioid PCA (first cohort); or multimodal analgesia including a single intraoperative administration of liposome bupivacaine (second cohort). Rescue analgesia was available to all patients. Primary outcome measures were postsurgical opioid use, hospital length of stay, and hospitalization costs. Incidence of opioid-related adverse events was also assessed. Results: Twenty-seven patients were enrolled, underwent the planned surgery, and did not meet any intraoperative exclusion criteria; 16 received liposome bupivacaine-based multimodal analgesia and eleven received the standard IV opioid PCA regimen. The multimodal regimen was associated with significant reductions in opioid use compared with the IV opioid PCA regimen (mean, 20 mg versus 112 mg; median, 6 mg versus 48 mg, respectively; P<0.01), postsurgical length of stay (median, 3.0 days versus 5.1 days, respectively; P<0.001), and hospitalization costs (geometric mean, $6482 versus $9282, respectively; P = 0.01). Conclusion: A liposome bupivacaine-based multimodal analgesic regimen resulted in statistically significant and clinically meaningful reductions in opioid consumption, shorter length of stay, and lower inpatient costs than an IV opioid-based analgesic regimen. © 2013 Marcet et al, publisher and licensee Dove Medical Press Ltd.


The International Association of HealthCare Professionals is pleased to welcome Herbert B. Newton, MD, FAAN, Professor of Neurology and Neurosurgery, to their prestigious organization with his upcoming publication in The Leading Physicians of the World. He is a highly-trained and qualified neurologist with expertise in all facets of his work. Dr. Herbert B. Newton has been practicing for more than 32 years, 25 of which were spent at Ohio State University and the Arthur G. James Cancer Hospital in Columbus, Ohio, having retired in June 2015. He is currently on staff at the Kettering Cancer Center and the Florida Hospital Cancer Institute, serving patients in Neuro-Oncology. As of December 31, 2015, Dr. Newton will be leaving Kettering Cancer Center, transitioning to be the full time Director of the Neuro-Oncology Center and CNS Oncology Program at the Florida Hospital Cancer Institute. Dr. Herbert B. Newton gained his Doctor of Medicine degree from the University of Buffalo in New York State in 1984. An internship then followed at Buffalo University Hospital, prior to completing his residency in Neurology at the University of Michigan Medical Center, and fellowship in Neuro-Oncology at the Memorial Sloan Kettering Cancer Center. He is the author of eight published books, and numerous articles and papers, along with remaining a member of the American Association for Cancer Research and the American Society of Clinical Oncology. Dr. Newton has also earned the coveted title of Fellow of the American Academy of Neurology, and attributes his success to his hard work and dedication. When not assisting patients, he likes to play music, and enjoys scuba diving. Learn more about Dr. Newton here: https://www.floridahospitalcancer.com/ and by reading his upcoming publication in The Leading Physicians of the World. FindaTopDoc.com is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics.  Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review.  FindaTopDoc.com features each doctor’s full professional biography highlighting their achievements, experience, patient reviews and areas of expertise.  A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life.  For more information about FindaTopDoc, visit: http://www.findatopdoc.com


Mikhail M.,Imperial College London | Mekhail Y.,George Washington University | Mekhail T.,Florida Hospital Cancer Institute
Current Oncology Reports | Year: 2012

Thymoma is a unique neoplasm of the anterior mediastinum that is frequently associated with indolent growth and a variety of paraneoplastic syndromes. One third of cases are detected during the evaluation of myasthenia gravis. Classification systems of thymoma have limited ability in accurately predicting prognosis and course of disease. Thus, staging is the only way to predict clinical behavior. Encapsulated tumors that are surgically resected carry the best prognosis. Adjuvant radiotherapy is recommended for incompletely excised and most invasive thymomas. Chemotherapy in anthracyclinebased chemotherapy remains the most effective chemotherapy for neoadjuvant, adjuvant or palliative treatment. © Springer Science+Business Media, LLC 2012.


Mazzone P.,Cleveland Clinic | Mekhail T.,Florida Hospital Cancer Institute
Respiratory Medicine | Year: 2012

Pulmonary physicians commonly develop relationships with lung cancer patients through the evaluation and staging of the disease prior to the discussion of treatment options with oncologists. Given the relationship that develops, a pulmonologist is often asked about aspects of the treatment plan that may be slightly outside of their comfort zone. The aim of this overview of medical treatment of non-small cell lung cancer is to provide the pulmonologist with an overview of the evidence guiding current practice so that they can be more comfortable answering their patients' questions while awaiting the expert opinion of the oncologist. We discuss standard chemotherapeutic agents, their common side effects, and their use in the adjuvant and neoadjuvant setting, as definitive therapy for locally advanced disease, as palliative therapy for advanced disease, and as maintenance therapy. We also discuss the mechanisms of action and side effects of targeted therapies (including inhibitors of vascular endothelial growth factor [VEGF], epidermal growth factor receptor [EGFR] signaling and the anaplastic lymphoma kinase [ALK] protein), their currently accepted uses, and upcoming phase III trials, the results of which may influence standard practice. © 2012 Elsevier Ltd. All rights reserved.


Luszczek W.,Cleveland Clinic | Cheriyath V.,Cleveland Clinic | Mekhail T.M.,Cleveland Clinic | Mekhail T.M.,Florida Hospital Cancer Institute | Borden E.C.,Cleveland Clinic
Molecular Cancer Therapeutics | Year: 2010

Because epigenetic inhibitors can reduce cancer cell proliferation, we tested the hypothesis that concurrent inhibition of histone acetylation and DNA methylation could synergistically reduce the viability of small cell lung cancer (SCLC) cells. Sub-IC50 concentrations of the DNA methyltransferase (DNMT) inhibitor decitabine (5-AZA-dC) and the histone deacetylase (HDAC) inhibitors (LBH589 or MGCD0103) synergistically reduced the proliferation of five of nine SCLC cell lines. Loss of viability of sensitive SCLC cells did not correlate with the inhibition of either DNMT1 or HDACs, suggesting nonepigenetic mechanisms for synergy between these two classes of epigenetic modulators. Because combinations of 5-AZA-dC and HDAC inhibitors had marginal effects on the apoptosis index, Comet assay was undertaken to assess DNA damage. MGCD0103 and 5AZA-dC cotreatment augmented DNA damage in SCLC cells, resulting in increased tail length and moment in Comet assays by 24 hours in sensitive cell lines (P < 0.01). Consistent with augmented DNA damage, combination of a DNMT and HDAC inhibitor markedly increased the levels of phospho-H2A.X in sensitive cells but not in resistant ones. Comparison of basal gene expression between resistant and sensitive cells identified markedly higher basal expression of IFN-stimulated genes in the resistant cell lines, suggesting that IFN-stimulated gene expression may determine SCLC cell sensitivity to epigenetic modulators or other DNA damaging agents. ©2010 AACR.


Alemany C.,Florida Hospital Cancer Institute
Current oncology reports | Year: 2014

Irinotecan is a very active chemotherapeutic agent used for the treatment of several malignancies, including colorectal cancer, gastroesophageal tumors, lung cancer, breast cancer, ovarian cancer, and primary brain tumors. Irinotecan exerts its antineoplastic effects through its active metabolite 7-ethyl-10-hydroxycamptothecin. This metabolite is also responsible for the classic side effects associated with irinotecan that include diarrhea and neutropenia. A pegylated form of this agent, etirinotecan pegol, is undergoing clinical development with the main goal of increasing its therapeutic efficacy and its safety. This agent decreases the maximal exposure to 7-ethyl-10-hydroxycamptothecin while providing continuous exposure to the treated tumor. The half-life of etirinotecan pegol is 50 days and it has been studied in different schedules: weekly, every other week, and once every 3 weeks. The maximum tolerated dose of etirinotecan pegol was found to be 145 mg/m(2). There have already been two phase II clinical trials published showing the efficacy of this novel agent in the treatment of metastatic ovarian and breast cancer. The side effect profile was acceptable for most patients, with a number of patients experiencing diarrhea and even neutropenia.


Alemany C.,Florida Hospital Cancer Institute
Current Oncology Reports | Year: 2014

Irinotecan is a very active chemotherapeutic agent used for the treatment of several malignancies, including colorectal cancer, gastroesophageal tumors, lung cancer, breast cancer, ovarian cancer, and primary brain tumors. Irinotecan exerts its antineoplastic effects through its active metabolite 7-ethyl-10-hydroxycamptothecin. This metabolite is also responsible for the classic side effects associated with irinotecan that include diarrhea and neutropenia. A pegylated form of this agent, etirinotecan pegol, is undergoing clinical development with the main goal of increasing its therapeutic efficacy and its safety. This agent decreases the maximal exposure to 7-ethyl-10-hydroxycamptothecin while providing continuous exposure to the treated tumor. The half-life of etirinotecan pegol is 50 days and it has been studied in different schedules: weekly, every other week, and once every 3 weeks. The maximum tolerated dose of etirinotecan pegol was found to be 145 mg/m2. There have already been two phase II clinical trials published showing the efficacy of this novel agent in the treatment of metastatic ovarian and breast cancer. The side effect profile was acceptable for most patients, with a number of patients experiencing diarrhea and even neutropenia. © 2014 Springer Science+Business Media New York.


Chowdhary S.A.,Florida Hospital Cancer Institute | Ryken T.,Iowa Spine and Brain Institute | Newton H.B.,Ohio State University
Journal of Neuro-Oncology | Year: 2015

Carmustine wafers (CW; Gliadel® wafers) are approved to treat newly-diagnosed high-grade glioma (HGG) and recurrent glioblastoma. Widespread use has been limited for several reasons, including concern that their use may preclude enrollment in subsequent clinical trials due to uncertainty about confounding of results and potential toxicities. This meta-analysis estimated survival following treatment with CW for HGG. A literature search identified relevant studies. Overall survival (OS), median survival, and adverse events (AEs) were summarized. Analysis of variance evaluated effects of treatment (CW vs non-CW) and diagnosis (new vs recurrent) on median survival. The analysis included 62 publications, which reported data for 60 studies (CW: n = 3,162; non-CW: n = 1,736). For newly-diagnosed HGG, 1-year OS was 67 % with CW and 48 % without; 2-year OS was 26 and 15 %, respectively; median survival was 16.4 ± 21.6 months and 13.1 ± 29.9 months, respectively. For recurrent HGG, 1-year OS was 37 % with CW and 34 % without; 2-year OS was 15 and 12 %, respectively; median survival was 9.7 ± 20.9 months and 8.6 ± 22.6 months, respectively. Effects of treatment (longer median survival with CW than without; P = 0.043) and diagnosis (longer median survival for newly-diagnosed HGG than recurrent; P < 0.001) on median survival were significant, with no significant treatment-by-diagnosis interaction (P = 0.620). The most common AE associated with wafer removal was surgical site infection (SSI); the most common AEs for repeat surgery were mass effect, SSI, hydrocephalus, cysts in resection cavity, acute hematoma, wound healing complications, and brain necrosis. These data may be useful in the context of utilizing CW in HGG management, and in designing future clinical trials to allow CW-treated patients to participate in experimental protocols. © 2015, The Author(s).


Rakowski J.A.,Florida Hospital Cancer Institute | Ahmad S.,Florida Hospital Cancer Institute | Holloway R.W.,Florida Hospital Cancer Institute
Expert Review of Anticancer Therapy | Year: 2012

Pegylated liposomal doxorubicin (PLD) was first approved for platinum-refractory ovarian cancer in 1999 and then received full approval for platinum-sensitive recurrent disease in 2005 by the US FDA. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Phase-II and III clinical trials of single-agent PLD in patients with platinum-sensitive recurrent ovarian cancer have reported overall mean survival times up to 29 months. Recent interest in PLD/carboplatin combination therapy for patients with platinum-sensitive recurrent ovarian cancer has been stirred from Phase-III trials reporting response rates, progressive-free survival and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. Clinical trials combining PLD with poly (ADP-ribose) polymerase inhibitors, triple angiokinase inhibitors and folate receptor inhibitors are enrolling or under development and may further augment the therapeutic efficacy of PLD. © 2012 Expert Reviews Ltd.

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