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Sai-Hong Ignatius Ou, Ramaswamy Govindan, Keith D Eaton, Gregory A Otterson, Martin E Gutierrez, Alain C Mita, Athanassios Argiris, Nicoletta M Brega, Tiziana Usari, Weiwei Tan, Steffan N Ho, Francisco Robert
INTRODUCTION: This phase I trial was conducted to determine the safety, maximum tolerated dose (MTD)/recommended phase II dose, and efficacy of crizotinib plus erlotinib in patients with advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: NSCLC patients with an Eastern Cooperative Oncology Group performance status of 0-2 after failure of 1-2 prior chemotherapy regimens were eligible. Erlotinib 100 mg was given continuously once daily (QD) starting between day -14 and -7; crizotinib 200 mg twice daily (BID; dose level 1) or 150 mg BID (dose level -1) was added continuously beginning on treatment cycle 1, day 1...
September 30, 2016: Journal of Thoracic Oncology
Fred R Hirsch, Ramaswamy Govindan, Zanete Zvirbule, Fadi Braiteh, Achim Rittmeyer, Cristóbal Belda-Iniesta, Dolores Isla, Thomas Cosgriff, Michelle Boyer, Masamichi Ueda, See Phan, David R Gandara
INTRODUCTION: The treatment options for squamous cell non-small-cell lung cancer (NSCLC) are limited. We assessed the efficacy and safety of onartuzumab plus platinum-doublet chemotherapy in previously untreated advanced squamous cell NSCLC. PATIENTS AND METHODS: The patients were randomized to receive onartuzumab plus paclitaxel plus carboplatin/cisplatin (n = 55) or placebo plus paclitaxel plus carboplatin/cisplatin (n = 54). Randomization was stratified by MET diagnostic status: MET immunohistochemistry (IHC)-positive (MET IHC 3+/2+) or MET IHC-negative (MET IHC 1+/0)...
June 4, 2016: Clinical Lung Cancer
David S Ettinger, Douglas E Wood, Wallace Akerley, Lyudmila A Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T Cheney, Lucian R Chirieac, Thomas A D'Amico, Thomas Dilling, Michael Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M Jahan, Ritsuko Komaki, Rudy P Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W Loo, Renato Martins, Gregory A Otterson, Jyoti D Patel, Katherine M Pisters, Karen Reckamp, Gregory J Riely, Steven E Schild, Theresa A Shapiro, Neelesh Sharma, Scott J Swanson, James Stevenson, Kurt Tauer, Stephen C Yang, Kristina Gregory, Miranda Hughes
These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN...
July 2016: Journal of the National Comprehensive Cancer Network: JNCCN
Saiama N Waqar, Philip D Bonomi, Ramaswamy Govindan, Fred R Hirsch, Gregory J Riely, Vassiliki Papadimitrakopoulou, Dickran Kazandjian, Sean Khozin, Erin Larkins, Dane J Dickson, Shakun Malik, Leora Horn, Andrea Ferris, Alice T Shaw, Pasi A Jänne, Tony S K Mok, Roy Herbst, Patricia Keegan, Richard Pazdur, Gideon M Blumenthal
Recent advances in molecularly targeted therapy and immunotherapy offer a glimmer of hope for potentially realizing the dream of personalized therapy for lung cancer. This article highlights current questions in clinical trial design, enrollment strategies and patient focused drug development, with particular emphasis on unique issues in trials of targeted therapy and immunotherapy.
September 2016: Journal of Thoracic Oncology
Daniel Morgensztern, Lingling Du, Saiama N Waqar, Aalok Patel, Pamela Samson, Siddhartha Devarakonda, Feng Gao, Cliff G Robinson, Jeffrey Bradley, Maria Baggstrom, Ashiq Masood, Ramaswamy Govindan, Varun Puri
BACKGROUND: Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC. METHODS: Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection between 2004 and 2011 were identified from the National Cancer Data Base and classified into four groups based on tumor size: 3...
October 2016: Journal of Thoracic Oncology
Balaji Govindan, Anil John Johnson, Sadasivan Nair Ajikumaran Nair, Bhaskaran Gopakumar, Karuna Sri Lakshmi Mallampalli, Ramaswamy Venkataraman, Konnath Chacko Koshy, Sabulal Baby
Melocanna baccifera is a unique bamboo which produces the largest fruits in the grass family. Its gregarious flowering once in 45-50 years in north east India and adjacent regions is a botanical enigma, resulting in a glut of fruits. Proper utilization of M. baccifera fruits is not extant, and huge quantities of fruits are left underexploited due to lack of scientific information on their chemical composition and nutritional potential. Here we report the nutritional properties of M. baccifera fruits, and the ecological significance of its fruiting...
2016: Scientific Reports
Charles Swanton, Ramaswamy Govindan
No abstract text is available yet for this article.
May 12, 2016: New England Journal of Medicine
Joshua D Campbell, Anton Alexandrov, Jaegil Kim, Jeremiah Wala, Alice H Berger, Chandra Sekhar Pedamallu, Sachet A Shukla, Guangwu Guo, Angela N Brooks, Bradley A Murray, Marcin Imielinski, Xin Hu, Shiyun Ling, Rehan Akbani, Mara Rosenberg, Carrie Cibulskis, Aruna Ramachandran, Eric A Collisson, David J Kwiatkowski, Michael S Lawrence, John N Weinstein, Roel G W Verhaak, Catherine J Wu, Peter S Hammerman, Andrew D Cherniack, Gad Getz, Maxim N Artyomov, Robert Schreiber, Ramaswamy Govindan, Matthew Meyerson
To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types...
June 2016: Nature Genetics
Saiama N Waqar, Janelle Mann, Maria Q Baggstrom, Muhammad Atif Waqar, Pooja Chitneni, Kristina Williams, Feng Gao, Daniel Morgensztern, Ramaswamy Govindan
BACKGROUND: Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis comprising of a 5-HT3 antagonist and dexamethasone. We performed a prospective study to define the incidence and risk factors for delayed chemotherapy-induced nausea and vomiting (CINV). METHODS: Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing chemotherapy (AUC 5 or above), but no prophylactic aprepitant were enrolled in the study...
June 2016: Acta Oncologica
David S Ettinger, Douglas E Wood, Wallace Akerley, Lyudmila A Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T Cheney, Lucian R Chirieac, Thomas A D'Amico, Thomas J Dilling, M Chris Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M Jahan, Ritsuko Komaki, Rudy P Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W Loo, Renato Martins, Gregory A Otterson, Jyoti D Patel, Katherine M Pisters, Karen Reckamp, Gregory J Riely, Steven E Schild, Theresa A Shapiro, Neelesh Sharma, James Stevenson, Scott J Swanson, Kurt Tauer, Stephen C Yang, Kristina Gregory, Miranda Hughes
These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies)...
March 2016: Journal of the National Comprehensive Cancer Network: JNCCN
Paul A Bunn, John D Minna, Alexander Augustyn, Adi F Gazdar, Youcef Ouadah, Mark A Krasnow, Anton Berns, Elisabeth Brambilla, Natasha Rekhtman, Pierre P Massion, Matthew Niederst, Martin Peifer, Jun Yokota, Ramaswamy Govindan, John T Poirier, Lauren A Byers, Murry W Wynes, David G McFadden, David MacPherson, Christine L Hann, Anna F Farago, Caroline Dive, Beverly A Teicher, Craig D Peacock, Jane E Johnson, Melanie H Cobb, Hans-Guido Wendel, David Spigel, Julien Sage, Ping Yang, M Catherine Pietanza, Lee M Krug, John Heymach, Peter Ujhazy, Caicun Zhou, Koichi Goto, Afshin Dowlati, Camilla Laulund Christensen, Keunchil Park, Lawrence H Einhorn, Martin J Edelman, Giuseppe Giaccone, David E Gerber, Ravi Salgia, Taofeek Owonikoko, Shakun Malik, Niki Karachaliou, David R Gandara, Ben J Slotman, Fiona Blackhall, Glenwood Goss, Roman Thomas, Charles M Rudin, Fred R Hirsch
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
Suresh Senan, Anthony Brade, Lu-Hua Wang, Johan Vansteenkiste, Shaker Dakhil, Bonne Biesma, Maite Martinez Aguillo, Joachim Aerts, Ramaswamy Govindan, Belén Rubio-Viqueira, Conrad Lewanski, David Gandara, Hak Choy, Tony Mok, Anwar Hossain, Neill Iscoe, Joseph Treat, Andrew Koustenis, Bélen San Antonio, Nadia Chouaki, Everett Vokes
PURPOSE: The phase III PROCLAIM study evaluated overall survival (OS) of concurrent pemetrexed-cisplatin and thoracic radiation therapy (TRT) followed by consolidation pemetrexed, versus etoposide-cisplatin and TRT followed by nonpemetrexed doublet consolidation therapy. PATIENTS AND METHODS: Patients with stage IIIA/B unresectable nonsquamous non-small-cell lung cancer randomly received (1:1) pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) intravenously every 3 weeks for three cycles plus concurrent TRT (60 to 66 Gy) followed by pemetrexed consolidation every 3 weeks for four cycles (arm A), or standard therapy with etoposide 50 mg/m(2) and cisplatin 50 mg/m(2) intravenously, every 4 weeks for two cycles plus concurrent TRT (60 to 66 Gy) followed by two cycles of consolidation platinum-based doublet chemotherapy (arm B)...
March 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Saiama N Waqar, Maria Q Baggstrom, Daniel Morgensztern, Kristina Williams, Caron Rigden, Ramaswamy Govindan
BACKGROUND: Pemetrexed is an antifolate chemotherapeutic agent approved for use in non-small cell lung cancer (NSCLC). The mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development and inhibited by temsirolimus. METHODS: We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC. RESULTS: Eight patients were enrolled in this study. The dose-limiting toxicities included grade 4 thrombocytopenia, grade 3 leukopenia and grade 3 neutropenia...
2016: Chemotherapy
Charles Lu, Mingchao Xie, Michael C Wendl, Jiayin Wang, Michael D McLellan, Mark D M Leiserson, Kuan-Lin Huang, Matthew A Wyczalkowski, Reyka Jayasinghe, Tapahsama Banerjee, Jie Ning, Piyush Tripathi, Qunyuan Zhang, Beifang Niu, Kai Ye, Heather K Schmidt, Robert S Fulton, Joshua F McMichael, Prag Batra, Cyriac Kandoth, Maheetha Bharadwaj, Daniel C Koboldt, Christopher A Miller, Krishna L Kanchi, James M Eldred, David E Larson, John S Welch, Ming You, Bradley A Ozenberger, Ramaswamy Govindan, Matthew J Walter, Matthew J Ellis, Elaine R Mardis, Timothy A Graubert, John F Dipersio, Timothy J Ley, Richard K Wilson, Paul J Goodfellow, Benjamin J Raphael, Feng Chen, Kimberly J Johnson, Jeffrey D Parvin, Li Ding
Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4% (acute myeloid leukaemia (AML)) to 19% (ovarian cancer), with a notably high frequency of 11% in stomach cancer. Burden testing identifies 13 cancer genes with significant enrichment of rare truncations, some associated with specific cancers (for example, RAD51C, PALB2 and MSH6 in AML, stomach and endometrial cancers, respectively)...
2015: Nature Communications
Ramaswamy Govindan, Sumithra J Mandrekar, David E Gerber, Geoffrey R Oxnard, Suzanne E Dahlberg, Jamie Chaft, Shakun Malik, Margaret Mooney, Jeffrey S Abrams, Pasi A Jänne, David R Gandara, Suresh S Ramalingam, Everett E Vokes
The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens...
December 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Saiama N Waqar, Leigh Boehmer, Daniel Morgensztern, Andrea Wang-Gillam, Steven Sorscher, Steven Lawrence, Feng Gao, Kalin Guebert, Kristina Williams, Ramaswamy Govindan
BACKGROUND: Influenza leads to significant morbidity and mortality in patients with cancer. Patients with cancer receiving chemotherapy may not mount an adequate immune response to the vaccine. We performed this pilot study to evaluate the immunogenicity of influenza vaccination in patients with cancer receiving chemotherapy. MATERIALS AND METHODS: During the 2011 to 2012 influenza season, patients undergoing chemotherapy for solid tumors were given trivalent inactivated influenza vaccine either on the day of chemotherapy (schedule A) or a week before chemotherapy (schedule B) by a single 0...
December 14, 2015: American Journal of Clinical Oncology
Sai-Hong Ignatius Ou, Jin Seok Ahn, Luigi De Petris, Ramaswamy Govindan, James Chih-Hsin Yang, Brett Hughes, Hervé Lena, Denis Moro-Sibilot, Alessandra Bearz, Santiago Viteri Ramirez, Tarek Mekhail, Alexander Spira, Walter Bordogna, Bogdana Balas, Peter N Morcos, Annabelle Monnet, Ali Zeaiter, Dong-Wan Kim
PURPOSE: Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. PATIENTS AND METHODS: Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC)...
March 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Marianne Paesmans, Camilo Garcia, Ching-Yee Oliver Wong, Edward F Patz, Ritsuko Komaki, Susanne Eschmann, Ramaswamy Govindan, Johan Vansteenkiste, Anne-Pascale Meert, Wouter K de Jong, Nasser Khaled Altorki, Kotaro Higashi, Angela Van Baardwijk, Gerben R Borst, Lieveke Ameye, Jean-Jacques Lafitte, Thierry Berghmans, Patrick Flamen, Ramon Rami-Porta, Jean-Paul Sculier
(18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients...
December 2015: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Saiama N Waqar, Sadaf H Waqar, Kathryn Trinkaus, Carlos A Gadea, Cliff G Robinson, Jeffrey Bradley, Mark A Watson, Varun Puri, Ramaswamy Govindan, Daniel Morgensztern
OBJECTIVE: We used brain radiotherapy as a surrogate for the presence of brain metastases in patients with non-small cell lung cancer (NSCLC) to determine the prevalence of brain metastases using the Surveillance Epidemiology and End Results database. METHODS: Patients with NSCLC diagnosed between 1988 and 1997 were subdivided according to brain radiotherapy status at presentation into: "none" or "radiation therapy indicated." We calculated the frequency of brain radiotherapy use in all patients...
October 15, 2015: American Journal of Clinical Oncology
Lakshmi Nayak, Lisa M DeAngelis, H Ian Robins, Ramaswamy Govindan, Shirish Gadgeel, Karen Kelly, James R Rigas, David M Peereboom, Steven S Rosenfeld, Alona Muzikansky, Ming Zheng, Patrick Urban, Lauren E Abrey, Antonio Omuro, Patrick Y Wen
BACKGROUND: Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. METHODS: Adult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m(2) every 3 weeks...
December 1, 2015: Cancer
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