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Melanoma: HELP
Articles by Kari L. Kendra
Based on 22 articles published since 2010
(Why 22 articles?)
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Between 2010 and 2020, K. Kendra wrote the following 22 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials. 2019

Jeter, Joanne M / Bowles, Tawnya L / Curiel-Lewandrowski, Clara / Swetter, Susan M / Filipp, Fabian V / Abdel-Malek, Zalfa A / Geskin, Larisa J / Brewer, Jerry D / Arbiser, Jack L / Gershenwald, Jeffrey E / Chu, Emily Y / Kirkwood, John M / Box, Neil F / Funchain, Pauline / Fisher, David E / Kendra, Kari L / Marghoob, Ashfaq A / Chen, Suephy C / Ming, Michael E / Albertini, Mark R / Vetto, John T / Margolin, Kim A / Pagoto, Sherry L / Hay, Jennifer L / Grossman, Douglas / Ellis, Darrel L / Kashani-Sabet, Mohammed / Mangold, Aaron R / Markovic, Svetomir N / Meyskens, Frank L / Nelson, Kelly C / Powers, Jennifer G / Robinson, June K / Sahni, Debjani / Sekulic, Aleksandar / Sondak, Vernon K / Wei, Maria L / Zager, Jonathan S / Dellavalle, Robert P / Thompson, John A / Weinstock, Martin A / Leachman, Sancy A / Cassidy, Pamela B. ·Department of Medicine, Divisions of Genetics and Oncology, The Ohio State University, Columbus, Ohio. · Department of Surgery, Intermountain Health Care, Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah. · Department of Medicine, The University of Arizona Cancer Center, Tucson, Arizona. · Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center Cancer Institute, Veterans Affairs Palo Alto Health Care System, Palo Alto, California. · Systems Biology and Cancer Metabolism, Program for Quantitative Systems Biology, University of California Merced, Merced, California. · Department of Dermatology, University of Cincinnati, Cincinnati, Ohio. · Department of Dermatology, Cutaneous Oncology Center, Columbia University Medical Center, New York, New York. · Department of Dermatologic Surgery, Mayo Clinic Minnesota, Rochester, Minnesota. · Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia. · Division of Dermatology, Veterans Affairs Medical Center, Atlanta, Georgia. · Departments of Surgical Oncology and Cancer Biology, Melanoma and Skin Cancer Center, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Melanoma and Skin Cancer Program, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. · Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. · Dermatology Service, U.S. Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, Colorado. · Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado. · Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. · Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts. · Department of Internal Medicine, Medical Oncology Division, The Ohio State University, Columbus, Ohio. · Memorial Sloan Kettering Skin Cancer Center and Department of Dermatology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, University of Wisconsin, School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. · Division of Surgical Oncology, Oregon Health & Science University, Portland, Oregon. · Department of Medical Oncology, City of Hope National Medical Center, Duarte, California. · Department of Allied Health Sciences, UConn Institute for Collaboration in Health, Interventions, and Policy, University of Connecticut, Storrs, Connecticut. · Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York. · Departments of Dermatology and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah. · Department of Dermatology, Vanderbilt University Medical Center and Division of Dermatology, Vanderbilt Ingram Cancer Center, Nashville, Tennessee. · Department of Medicine, Tennessee Valley Healthcare System, Nashville Veterans Affairs Medical Center, Nashville, Tennessee. · Center for Melanoma Research and Treatment, California Pacific Medical Center, San Francisco, California. · Department of Dermatology, Mayo Clinic, Scottsdale, Arizona. · Department of Hematology and Oncology, Mayo Clinic, Rochester, Minnesota. · Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Dermatology, University of Iowa, Iowa City, Iowa. · Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Dermatology, Boston Medical Center, Boston, Massachusetts. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida. · Departments of Oncologic Sciences and Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida. · Department of Dermatology, University of California, San Francisco, San Francisco, California. · Dermatology Service, San Francisco Veterans Affairs Medical Center, San Francisco, California. · Department of Sarcoma, H. Lee Moffitt Cancer Center, Tampa, Florida. · Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington. · Center for Dermatoepidemiology, Veterans Affairs Medical Center, Providence, Rhode Island. · Department of Dermatology, Brown University, Providence, Rhode Island. · Department of Epidemiology, Brown University, Providence, Rhode Island. · Department of Dermatology, Rhode Island Hospital, Providence, Rhode Island. · Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. ·Cancer · Pubmed #30281145.

ABSTRACT: Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

2 Review Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy. 2017

Johnson, Mariah M / Leachman, Sancy A / Aspinwall, Lisa G / Cranmer, Lee D / Curiel-Lewandrowski, Clara / Sondak, Vernon K / Stemwedel, Clara E / Swetter, Susan M / Vetto, John / Bowles, Tawnya / Dellavalle, Robert P / Geskin, Larisa J / Grossman, Douglas / Grossmann, Kenneth F / Hawkes, Jason E / Jeter, Joanne M / Kim, Caroline C / Kirkwood, John M / Mangold, Aaron R / Meyskens, Frank / Ming, Michael E / Nelson, Kelly C / Piepkorn, Michael / Pollack, Brian P / Robinson, June K / Sober, Arthur J / Trotter, Shannon / Venna, Suraj S / Agarwala, Sanjiv / Alani, Rhoda / Averbook, Bruce / Bar, Anna / Becevic, Mirna / Box, Neil / E Carson, William / Cassidy, Pamela B / Chen, Suephy C / Chu, Emily Y / Ellis, Darrel L / Ferris, Laura K / Fisher, David E / Kendra, Kari / Lawson, David H / Leming, Philip D / Margolin, Kim A / Markovic, Svetomir / Martini, Mary C / Miller, Debbie / Sahni, Debjani / Sharfman, William H / Stein, Jennifer / Stratigos, Alexander J / Tarhini, Ahmad / Taylor, Matthew H / Wisco, Oliver J / Wong, Michael K. ·Department of Dermatology, Oregon Health & Science University, 3303 SW Bond Ave., Portland, OR, USA. · University of Utah, Salt Lake City, UT, USA. · University of Washington, Seattle, WA, USA. · University of Arizona Cancer Center, Tucson, AZ, USA. · Moffitt Cancer Center, Tampa, FL, USA. · Oregon Health & Science University, Portland, OR, USA. · Stanford University Medical Center & VA Palo Alto Health Care System, Palo Alto, CA, USA. · Intermountain Healthcare & University of Utah, Salt Lake City, UT, USA. · University of Colorado, Aurora, CO, USA. · Columbia University, New York, NY, USA. · The Ohio State University, Columbus, OH, USA. · Harvard Medical School, Boston, MA, USA. · University of Pittsburgh, Pittsburgh, PA, USA. · Mayo Clinic Arizona, Scottsdale, AZ, USA. · University of California, Irvine, Orange, CA, USA. · University of Pennsylvania, Philadelphia, PA, USA. · The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Emory University & Atlanta VA Medical Center, Atlanta, GA, USA. · Northwestern University Feinberg School of Medicine, Chicago, IL USA. · Inova Medical Group, Fairfax, VA, USA. · St Luke's University Hospital & Temple University, Bethlehem, PA, USA. · Boston University, Boston, MA, USA. · Case Western Reserve University, Cleveland, OH, USA. · University of Missouri, Columbia, MO, USA. · Vanderbilt University, Nashville, TN, USA. · Harvard Medical School & Massachusetts General Hospital, Charlestown, MA, USA. · Winship Cancer Institute of Emory University, Atlanta, GA, USA. · The Christ Hospital, Cincinnati, OH, USA. · City of Hope National Cancer Center, Duarte, CA, USA. · Mayo Clinic Rochester, MN, USA. · Johns Hopkins University, Baltimore, MD. · NYU Langone Medical Center, New York, NY, USA. · Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece. · Bend Memorial Clinic, Bend, OR, USA. · University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Melanoma Manag · Pubmed #28758010.

ABSTRACT: Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

3 Clinical Trial A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma. 2019

Suarez-Kelly, Lorena P / Levine, Kala M / Olencki, Thomas E / Del Campo, Sara E Martin / Streacker, Elizabeth A / Brooks, Taylor R / Karpa, Volodymyr I / Markowitz, Joseph / Bingman, Anissa K / Geyer, Susan M / Kendra, Kari L / Carson, William E. ·Comprehensive Cancer Center, The Ohio State University, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, N924 Doan Hall 410 W. 10th Ave, Columbus, OH, 43210-1228, USA. · Medical Oncology, Department of Internal Medicine, The Ohio State University, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA. · Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. · Promedica Toledo Hospital, Toledo, OH, USA. · Division of Rheumatology and Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA. · Hematology, Department of Internal Medicine, The Ohio State University, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA. · Comprehensive Cancer Center, The Ohio State University, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, N924 Doan Hall 410 W. 10th Ave, Columbus, OH, 43210-1228, USA. william.carson@osumc.edu. · Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. william.carson@osumc.edu. ·Cancer Immunol Immunother · Pubmed #30725205.

ABSTRACT: -- No abstract --

4 Clinical Trial Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases. 2017

Williams, Noelle L / Wuthrick, Evan J / Kim, Hyun / Palmer, Joshua D / Garg, Shivank / Eldredge-Hindy, Harriet / Daskalakis, Constantine / Feeney, Kendra J / Mastrangelo, Michael J / Kim, Lyndon J / Sato, Takami / Kendra, Kari L / Olencki, Thomas / Liebner, David A / Farrell, Christopher J / Evans, James J / Judy, Kevin D / Andrews, David W / Dicker, Adam P / Werner-Wasik, Maria / Shi, Wenyin. ·Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University and Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Ohio State University, Columbus, Ohio. · Department of Radiation Oncology, Baystate Medical Center, Springfield, Massachusetts. · Department of Biostatistics, Thomas Jefferson University, Philadelphia, Pennsylvania. · Department of Medical Oncology, Sidney Kimmel Medical College at Thomas Jefferson University and Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania. · Division of Medical Oncology, Ohio State University, Columbus, Ohio. · Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University and Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania. · Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University and Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania. Electronic address: Wenyin.Shi@jefferson.edu. ·Int J Radiat Oncol Biol Phys · Pubmed #28816150.

ABSTRACT: PURPOSE: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. METHODS AND MATERIALS: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design. The primary endpoint was to determine the maximum tolerable dose of ipilimumab combined with radiation therapy. The secondary endpoints were overall survival, intracranial and extracranial control, progression-free survival, and toxicity. The ClinicalTrials.gov registration number is NCT01703507. RESULTS: The characteristics of the 16 patients enrolled between 2011 and 2014 were mean age, 60 years; median number of brain metastases, 2 (range 1->10); and number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), and ipilimumab 3 mg/kg (n=7) or 10 mg/kg (n=9). The median follow-up was 8 months (arm A) and 10.5 months (arm B). A total of 21 grade 1 to 2 neurotoxic effects occurred, with no dose-limiting toxicities. One patient experienced grade 3 neurotoxicity before ipilimumab administration. Ten additional grade 3 toxicities were reported, with gastrointestinal toxicities (n=5; 31%) the most common. No patient developed grade 4 or 5 toxicity. The median progression-free survival and overall survival in arm A was 2.5 months and 8 months and in arm B was 2.1 months and not reached, respectively. CONCLUSIONS: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early because of slow accrual but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced dose-limiting toxicity. Larger studies, including those with combination checkpoint inhibitor therapy and SRS, are warranted.

5 Clinical Trial A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. 2015

Hersh, E M / Del Vecchio, M / Brown, M P / Kefford, R / Loquai, C / Testori, A / Bhatia, S / Gutzmer, R / Conry, R / Haydon, A / Robert, C / Ernst, S / Homsi, J / Grob, J J / Kendra, K / Agarwala, S S / Li, M / Clawson, A / Brachmann, C / Karnoub, M / Elias, I / Renschler, M F / Hauschild, A. ·Department of Medicine, Arizona Cancer Center, Tucson, USA ehersh@azcc.arizona.edu. · Department of Medical Oncology, Fondazione IRCCS National Tumor Institute, Milan, Italy. · Cancer Clinical Trials Unit, Royal Adelaide Hospital and School of Medicine, University of Adelaide, Adelaide. · Sydney West Cancer Trials Centre/Westmead Hospital and Melanoma Institute Australia, University of Sydney, North Sydney, Australia. · Department of Dermatology, University of Mainz, Mainz, Germany. · Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milan, Italy. · Department of Medicine, Seattle Cancer Care Alliance, Seattle, USA. · Department of Dermatology and Oncology, Hannover Medical School, Hannover, Germany. · Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA. · Department of Medical Oncology, Alfred Hospital, Melbourne, Australia. · Demartology Unit, Department of Medicine, The Gustave Roussy Cancer Institute, Villejuif, France. · Department of Medical Oncology, London Health Sciences Center-London Regional Cancer Program, London, Canada. · Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA. · Department of Dermatology, Timone Hospital, APHM and Aix-Marseille University, Marseille, France. · Department of Internal Medicine, Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus. · Department of Hematology and Oncology, St Luke's Cancer Center and Temple University, Bethlehem. · Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA. · Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany. ·Ann Oncol · Pubmed #26410620.

ABSTRACT: BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.

6 Clinical Trial A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. 2014

Monk, Paul / Lam, Elaine / Mortazavi, Amir / Kendra, Kari / Lesinski, Gregory B / Mace, Thomas A / Geyer, Susan / Carson, William E / Tahiri, Sanaa / Bhinder, Arvinder / Clinton, Steven K / Olencki, Thomas. ·*Division of Medical Oncology, Comprehensive Cancer Center, The Ohio State University, and Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, OH †Division of Medical Oncology, University of Colorado Denver School of Medicine, Denver, CO. ·J Immunother · Pubmed #24598448.

ABSTRACT: This study was designed to evaluate the safety and feasibility of high-dose interleukin-2 (HD IL-2) followed by sorafenib in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC). Biomarkers relevant to the antitumor effects of IL-2 that may be altered by sorafenib including the percentages of natural T-regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and STAT5 phosphorylation (pSTAT5) in T cells were evaluated. We hypothesized that the proposed treatment schedule is feasible and safe and may lead to enhanced tumor response. A phase I dose escalation trial was conducted in patients with either metastatic RCC or MM. HD IL-2 (600,000 IU/kg IV q8h × 8-12 doses) was administered on days 1-5 and 15-19, followed by sorafenib on days 29-82. The sorafenib dose was escalated. The percentage of Tregs, MDSC, and pSTAT5 in T cells were evaluated in peripheral blood by flow cytometry. Twelve of the 18 patients were evaluable for dose-limiting toxicity. No dose-limiting toxicity was observed. The treatment-related toxicity was predictable and did not seem to be additive with this schedule of administration. Partial responses were seen in 3 patients. No significant changes in the percentage of circulating Treg and MDSC were observed, whereas sorafenib did not adversely affect the ability of IL-2 to induce pSTAT5 in T cells. HD IL-2 followed by sorafenib was safe and feasible in patients with MM and RCC and did not adversely affect T-cell signaling through STAT5 in response to IL-2.

7 Clinical Trial A phase I trial of bortezomib and interferon-α-2b in metastatic melanoma. 2014

Markowitz, Joseph / Luedke, Eric A / Grignol, Valerie P / Hade, Erinn M / Paul, Bonnie K / Mundy-Bosse, Bethany L / Brooks, Taylor R / Dao, Thao-Vi / Kondalasula, Sri V / Lesinski, Gregory B / Olencki, Thomas / Kendra, Kari L / Carson, William E. ·Divisions of *Medical Oncology †Surgical Oncology ‡Center for Biostatistics, The Ohio State University, Columbus, OH. ·J Immunother · Pubmed #24316557.

ABSTRACT: The possibility that cytokine administration could enhance the antitumor effects of proteasome inhibition was explored. It was found that coadministration of bortezomib and interferon-α (IFN-α) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. A phase I study was conducted to determine the tolerability and the maximum tolerated dose of bortezomib when administered in combination with IFN-α-2b to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-α subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-α thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-α. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men; median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3), and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1). The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a partial response, and 7 had stable disease. Progression-free survival was 2.5 months, and overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-α to induce phosphorylation of STAT1 in circulating immune cells; however, it did lead to reduced plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-α can be safely administered to melanoma patients.

8 Clinical Trial Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. 2013

Ribas, Antoni / Kefford, Richard / Marshall, Margaret A / Punt, Cornelis J A / Haanen, John B / Marmol, Maribel / Garbe, Claus / Gogas, Helen / Schachter, Jacob / Linette, Gerald / Lorigan, Paul / Kendra, Kari L / Maio, Michele / Trefzer, Uwe / Smylie, Michael / McArthur, Grant A / Dreno, Brigitte / Nathan, Paul D / Mackiewicz, Jacek / Kirkwood, John M / Gomez-Navarro, Jesus / Huang, Bo / Pavlov, Dmitri / Hauschild, Axel. ·Division of Hematology-Oncology, 11-934 Factor Building, UCLA Medical Center, 10833 Le Conte Ave, Los Angeles, CA 90095-1782, USA. aribas@mednet.ucla.edu ·J Clin Oncol · Pubmed #23295794.

ABSTRACT: PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. PATIENTS AND METHODS: Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). RESULTS: In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. CONCLUSION: This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

9 Clinical Trial Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma. 2012

Galanis, Evanthia / Markovic, Svetomir N / Suman, Vera J / Nuovo, Gerard J / Vile, Richard G / Kottke, Timothy J / Nevala, Wendy K / Thompson, Michael A / Lewis, Jean E / Rumilla, Kandelaria M / Roulstone, Victoria / Harrington, Kevin / Linette, Gerald P / Maples, William J / Coffey, Matt / Zwiebel, James / Kendra, Kari. ·Mayo Clinic, Rochester, Minnesota 55905, USA. galanis.evanthia@mayo.edu ·Mol Ther · Pubmed #22871663.

ABSTRACT: Reovirus, a replication competent RNA virus, has preclinical activity against melanoma lines and xenografts. We conducted a phase II trial of reovirus in metastatic melanoma patients. Patients received 3 × 10(10) TCID50 on days 1-5 of each 28 day cycle, administered intravenously. Twenty-one eligible patients were enrolled. Treatment was well tolerated without any dose reductions having to be implemented. Post-treatment biopsy samples were obtained in 15 patients, 13/15 contained adequate tumor for correlative analysis. In two patients, productive reoviral replication (viral antigen coexpression with tubulin) was demonstrated, despite increase in neutralizing antibody titers. There were no objective responses although 75-90% tumor necrosis, consistent with treatment effect, was observed in one patient who had metastatic lesions surgically removed. Median time to progression and survival were 45 days (range 13-96 days) and 165 days (range 15 days-15.8 months) respectively. In conclusion, reovirus treatment was well tolerated in metastatic melanoma patients; viral replication was demonstrated in biopsy samples. Based on preclinical data showing synergy with taxane and platinum compounds, a phase II combination trial in metastatic melanoma patients is ongoing.

10 Clinical Trial A phase 2 trial of bevacizumab and high-dose interferon alpha 2B in metastatic melanoma. 2011

Grignol, Valerie P / Olencki, Thomas / Relekar, Kiran / Taylor, Cynthia / Kibler, Amanda / Kefauver, Cheryl / Wei, Lai / Walker, Michael J / Chen, Helen X / Kendra, Kari / Carson, William E. ·Division of Surgical Oncology, The Ohio State University, Columbus, OH 43210, USA. ·J Immunother · Pubmed #21654521.

ABSTRACT: Bevacizumab is a humanized recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, an agent with proangiogenic effects in melanoma. Interferon alpha (IFN-α) has antiangiogenic properties through its ability to downregulate basic-fibroblast growth factor levels. We hypothesized that the coadministration of these agents would lead to tumor regression. Patients with metastatic melanoma received bevacizumab 15 mg/kg intravenously on day 1 of the 2-week cycle. IFN-α was administered thrice weekly at 5 MU/m subcutaneously during cycle 1 and was increased to 10 MU/m during cycle 2. Patients were restaged every 6 cycles. Patients with stable disease or a response continued with therapy. Baseline serum vascular endothelial growth factor and fibroblast growth factor were measured. Twenty-five patients were accrued. Mean age was 58.4 years. Eleven patients required IFN-α dose reductions due to toxicity. Common grade 3 toxicities associated with IFN-α included fatigue and myalgia. Bevacizumab administration was associated with grade 2-3 proteinuria in 6 patients. Grade 4 adverse events were pulmonary embolus (1), myocardial infarction (1), and stroke (1). Six patients had a partial response, and 5 patients exhibited stable disease that lasted more than 24 weeks (range: 30 to 122 wk). Median progression-free survival and overall survival were 4.8 and 17 months, respectively. Significantly lower fibroblast growth factor levels were observed in patients with a partial response compared to those with stable or progressive disease (P=0.040). Administration of bevacizumab with IFN led to a clinical response in 24% of patients with stage IV melanoma and stabilization of disease in another 20% of patients. This regimen has activity in advanced melanoma.

11 Clinical Trial gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. 2011

Schwartzentruber, Douglas J / Lawson, David H / Richards, Jon M / Conry, Robert M / Miller, Donald M / Treisman, Jonathan / Gailani, Fawaz / Riley, Lee / Conlon, Kevin / Pockaj, Barbara / Kendra, Kari L / White, Richard L / Gonzalez, Rene / Kuzel, Timothy M / Curti, Brendan / Leming, Phillip D / Whitman, Eric D / Balkissoon, Jai / Reintgen, Douglas S / Kaufman, Howard / Marincola, Francesco M / Merino, Maria J / Rosenberg, Steven A / Choyke, Peter / Vena, Don / Hwu, Patrick. ·Indiana University Health Goshen Center for Cancer Care, Goshen, IN 46526, USA. dschwart@iuhealth.org ·N Engl J Med · Pubmed #21631324.

ABSTRACT: BACKGROUND: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. METHODS: We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. RESULTS: The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06). CONCLUSIONS: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.).

12 Clinical Trial A pilot study of bevacizumab and interferon-α2b in ocular melanoma. 2011

Guenterberg, Kristan D / Grignol, Valerie P / Relekar, Kiran V / Varker, Kimberly A / Chen, Helen X / Kendra, Kari L / Olencki, Thomas E / Carson, William E. ·Division of Surgical Oncology, The Ohio State University, Columbus, Ohio 43210, USA. ·Am J Clin Oncol · Pubmed #20458209.

ABSTRACT: OBJECTIVES: We hypothesized that administration of bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, in combination with high-dose interferon-alpha2b (IFN-α2b), an inhibitor of basic fibroblast growth factor, would have clinical activity in patients with metastatic ocular melanoma. METHODS: Patients with metastatic ocular melanoma received bevacizumab (15 mg/kg intravenously every 2 weeks) plus IFN-α2b (5 MU/m subcutaneously 3 times weekly for 2 weeks followed by a dose of 10 MU/m subcutaneously thereafter). Patients exhibiting a clinical response or stabilization of disease were treated until disease progression. RESULTS: In this pilot study, 5 patients were treated (3 men, 2 women) with a mean age of 63.8 years (range, 53-71 years). Overall, the regimen was well-tolerated. The following adverse events were noted: grade 3 dyspnea (2 patients), grade 3 and 4 fatigue (2), grade 3 muscle weakness (1), grade 3 anorexia (1), grade 1 and 2 proteinuria (2), and grade 3 diarrhea (1). All adverse events resolved with a treatment holiday or dose reduction. One patient had reduction in tumor burden of 23% by Response Evaluation Criteria in Solid Tumors criteria and 2 patients had stabilization of disease lasting 28 and 36 weeks, respectively. Two patients failed to respond and progressed after 6 and 7 weeks of therapy. CONCLUSION: Bevacizumab and IFN-α2b were well tolerated in this patient population, and clinical activity was observed. Further study of high-dose IFN-α2b in combination with bevacizumab in this setting is warranted.

13 Article Hybrid Capture-Based Genomic Profiling Identifies BRAF V600 and Non-V600 Alterations in Melanoma Samples Negative by Prior Testing. 2019

Boussemart, Lise / Nelson, Annie / Wong, Michael / Ross, Jeffrey S / Sosman, Jeffrey / Mehnert, Janice / Daniels, Gregory / Kendra, Kari / Ali, Siraj Mahamed / Miller, Vincent A / Schrock, Alexa B. ·Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France. · University of Rennes, CNRS, IGDR, UMR 6290, Rennes, France. · Foundation Medicine, Inc., Cambridge, Massachusetts, USA. · MD Anderson Cancer Center, Houston, Texas, USA. · Department of Pathology, SUNY Upstate Medical University, Syracuse, New York, USA. · Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA. · Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA. · Moores Cancer Center, University of California San Diego, La Jolla, California, USA. · The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA. · Foundation Medicine, Inc., Cambridge, Massachusetts, USA aschrock@foundationmedicine.com. ·Oncologist · Pubmed #30683711.

ABSTRACT: BACKGROUND: BRAF and MEK inhibitors are approved for BRAF V600-mutated advanced melanoma, with response rates of up to 70%. Responses to targeted therapies have also been observed for diverse non-V600 BRAF alterations. Thus, sensitive, accurate, and broad detection of BRAF alterations is critical to match patients with available targeted therapies. MATERIALS AND METHODS: Pathology reports were reviewed for 385 consecutive melanoma cases with BRAF mutations or rearrangements identified using a hybrid capture-based next-generation sequencing comprehensive genomic profiling (CGP) assay during the course of clinical care. RESULTS: Records of prior BRAF molecular testing were available for 79 (21%) cases. Of cases with BRAF V600 mutations, 11/57 (19%) with available data were negative by prior BRAF testing. Prior negative BRAF results were also identified in 16/20 (80%) cases with non-V600 mutations, 2 of which harbored multiple BRAF alterations, and in 2/2 (100%) cases with activating BRAF fusions. Clinical outcomes for a subset of patients are presented. CONCLUSION: CGP identifies diverse activating BRAF alterations in a significant fraction of cases with prior negative testing. Given the proven clinical benefit of BRAF/MEK inhibitors in BRAF-mutated melanoma, CGP should be considered for patients with metastatic melanoma, particularly if other testing is negative. IMPLICATIONS FOR PRACTICE: Published guidelines for melanoma treatment recommend BRAF mutational analysis, but little guidance is provided as to selection criteria for testing methodologies, or as to clinical implications for non-V600 alterations. This study found that hybrid capture-based next-generation sequencing can detect BRAF alterations in samples from a significant fraction of patients with advanced melanoma with prior negative BRAF results. This study highlights the need for oncologists and pathologists to be critically aware of coverage and sensitivity limitations of various assays, particularly regarding non-V600E alterations, of which many are potentially targetable.

14 Article Surveillance strategies in the follow-up of melanoma patients: too much or not enough? 2017

Kurtz, James / Beasley, Georgia M / Agnese, Doreen / Kendra, Kari / Olencki, Thomas E / Terando, Alicia / Howard, J Harrison. ·Department of Surgery, Doctors Hospital, Columbus, Ohio. Electronic address: james.kurtz@ohiohealth.com. · Division of Surgical Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio. · Division of Medical Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio. ·J Surg Res · Pubmed #28624057.

ABSTRACT: BACKGROUND: After appropriate initial therapy for patients with stage II-III melanoma, there is no consensus regarding surveillance. Thus, follow-up is highly variable among institutions and individual providers. The National Comprehensive Cancer Network recommends routine clinical examination and consideration of imaging for stage IIB-IIIC every 3-12 mo with no distinction between stages. Detection of recurrence is important as novel systemic therapies and surgical resection of recurrence may provide survival benefits. METHODS: We retrospectively reviewed 369 patients with stage II and III melanoma treated at Ohio State University from 2009-2015, who underwent surgery as primary therapy. Two hundred forty-seven patients who were followed for a minimum of 6 mo after surgical resection to achieve no evidence of disease status (NED) were included in this analysis. One hundred twenty-two were lost to follow-up after surgery and were excluded. RESULTS: The rate of recurrence for stage IIA/IIB patients was 11% (14/125). Eleven of the 14 (79%) recurrences were detected by clinical symptoms or physical examination. Thirty-nine percent (49/125) of stage IIA or IIB patients were followed by clinical examination only, whereas 61% (76/125) were followed with at least two serial chest x-rays. The median time to first chest x-ray after NED status was 4.7 mo (n = 76), median time to second chest x-ray after NED status was 12.7 mo (n = 76), and 66% (50/76) continued to have additional serial chest x-rays. At median follow-up of 35 mo for the 125 patients with stage IIA/IIB, there was no difference in survival between those followed clinically (95% [95% CI: 0.88-0.99]) versus those followed with at least two serial x-rays (96% [95% CI: 0.89-0.98]). For stage IIC/IIIA-C patients, recurrence was detected in 23% (28/122) at median follow-up 31.2 mo. Fifty percent of recurrences were detected by imaging in asymptomatic patients, whereas 50% (14/28) had recurrence detected on imaging associated clinical findings. Eighty-seven percent (106/122) of stage IIC/IIIA-C patients were followed with at least two serial whole body positron emission tomography/computed tomography (CT) scans or whole body CT scans plus brain magnetic resonance imaging; median time between NED status and second scan was 10.3 mo. Of stage IIC/IIIA-C patients with recurrence, 57% (16/28) went on to surgical resection of the recurrence, whereas 11 (39%) patients received B-RAF inhibitor therapy, immune blockade therapy, or combination therapy. CONCLUSIONS: For stage IIA and IIB melanoma, surveillance chest x-rays did not improve survival compared to physical examination alone. However, for stage IIC and IIIA-C melanoma, where the recurrence rates are higher, routine whole body imaging detected 50% of recurrences leading to additional surgery and/or treatment with novel systemic therapies for the majority of patients. Detection of melanoma recurrence is important and specific substage should be used to stratify risk and define appropriate follow-up.

15 Article The Exportin-1 Inhibitor Selinexor Exerts Superior Antitumor Activity when Combined with T-Cell Checkpoint Inhibitors. 2017

Farren, Matthew R / Hennessey, Rebecca C / Shakya, Reena / Elnaggar, Omar / Young, Gregory / Kendra, Kari / Landesman, Yosef / Elloul, Sivan / Crochiere, Marsha / Klebanov, Boris / Kashyap, Trinayan / Burd, Christin E / Lesinski, Gregory B. ·Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia. · Department of Molecular Genetics, The Ohio State University, Columbus, Ohio. · Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio. · Target Validation Shared Resource, The Ohio State University, Columbus, Ohio. · Division of Internal Medicine, The Ohio State University, Columbus, Ohio. · Center for Biostatistics, The Ohio State University, Columbus, Ohio. · Karyopharm Therapeutics, Newton, Massachusetts. · Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia. gregory.b.lesinski@emory.edu. ·Mol Cancer Ther · Pubmed #28148715.

ABSTRACT: Selinexor, a selective inhibitor of nuclear export (SINE) compound targeting exportin-1, has previously been shown to inhibit melanoma cell growth

16 Article MicroRNA profiling of patient plasma for clinical trials using bioinformatics and biostatistical approaches. 2016

Markowitz, Joseph / Abrams, Zachary / Jacob, Naduparambil K / Zhang, Xiaoli / Hassani, John N / Latchana, Nicholas / Wei, Lai / Regan, Kelly E / Brooks, Taylor R / Uppati, Sarvani R / Levine, Kala M / Bekaii-Saab, Tanios / Kendra, Kari L / Lesinski, Gregory B / Howard, J Harrison / Olencki, Thomas / Payne, Philip R / Carson, William E. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL; Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Department of Oncologic Sciences, USF Morsani School of Medicine, Tampa, FL; Division of Medical Oncology, The Ohio State University Wexner Medical Center. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Department of Biomedical Informatics. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Department of Radiation Oncology. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Center for Biostatistics. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL. · Department of Surgery, The Ohio State University, Columbus, OH, USA. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Division of Medical Oncology, The Ohio State University Wexner Medical Center. · Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Department of Surgery, The Ohio State University, Columbus, OH, USA. ·Onco Targets Ther · Pubmed #27729802.

ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs that function to repress translation of mRNA transcripts and contribute to the development of cancer. We hypothesized that miRNA array-based technologies work best for miRNA profiling of patient-derived plasma samples when the techniques and patient populations are precisely defined. METHODS: Plasma samples were obtained from five sources: melanoma clinical trial of interferon and bortezomib (12), purchased normal donor plasma samples (four), gastrointestinal tumor bank (nine), melanoma tumor bank (ten), or aged-matched normal donors (eight) for the tumor bank samples. Plasma samples were purified for miRNAs and quantified using NanoString RESULTS: With the prospectively collected samples, fewer plasma samples demonstrated visible hemolysis due to increased attention to eliminating factors, such as increased pressure during phlebotomy, small gauge needles, and multiple punctures. Cancer patients enrolled in a melanoma clinical study exhibited the clearest pattern of miRNA expression as compared to normal donors in both the rank-based analytical method and standard biostatistical array approaches. For the patients from the tumor banks, fewer miRNAs (<5) were found to be differentially expressed and the false positive rate was relatively high. CONCLUSION: In order to obtain consistent results for NanoString miRNA arrays, it is imperative that patient cohorts have similar clinical characteristics with a uniform sample preparation procedure. A clinical workflow has been optimized to collect patient samples to study plasma miRNAs.

17 Article Bilateral Choroidopathy and Serous Retinal Detachments During Ipilimumab Treatment for Cutaneous Melanoma. 2015

Mantopoulos, Dimosthenis / Kendra, Kari L / Letson, Alan D / Cebulla, Colleen M. ·Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Wexner Medical Center, Columbus. · Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Wexner Medical Center, Columbus. ·JAMA Ophthalmol · Pubmed #25974108.

ABSTRACT: -- No abstract --

18 Article Cotreatment of hairy cell leukemia and melanoma with the BRAF inhibitor dabrafenib. 2015

Blachly, James S / Lozanski, Gerard / Lucas, David M / Grever, Michael R / Kendra, Kari / Andritsos, Leslie A. ·From the Division of Hematology, Department of Internal Medicine, Department of Pathology, and Division of Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio. ·J Natl Compr Canc Netw · Pubmed #25583765.

ABSTRACT: The activating BRAF mutation p.V600E has been identified in many cancers, including colon and lung adenocarcinomas, papillary thyroid cancer, malignant melanoma, and hairy cell leukemia (HCL). Malignant melanoma and HCL are of particular interest because of both the high proportion of cases harboring the mutation and the dramatic responses to BRAF inhibitor therapy reported in the literature. This report presents a patient with HCL and malignant melanoma with the BRAF p.V600E mutation, and discusses the successful treatment of both cancers with the BRAF inhibitor dabrafenib.

19 Article Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma. 2014

Damodaran, Senthil / Mrozek, Ewa / Liebner, David / Kendra, Kari. ·From the Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio. ·J Natl Compr Canc Netw · Pubmed #25505207.

ABSTRACT: High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma.

20 Article Novel small molecule XPO1/CRM1 inhibitors induce nuclear accumulation of TP53, phosphorylated MAPK and apoptosis in human melanoma cells. 2014

Yang, Jennifer / Bill, Matthew A / Young, Gregory S / La Perle, Krista / Landesman, Yosef / Shacham, Sharon / Kauffman, Michael / Senapedis, William / Kashyap, Trinayan / Saint-Martin, Jean-Richard / Kendra, Kari / Lesinski, Gregory B. ·Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America. · Center for Biostatistics, The Ohio State University, Columbus, Ohio, United States of America. · Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America. · Karyopharm Therapeutics, Natick, Massachusetts, United States of America. ·PLoS One · Pubmed #25057921.

ABSTRACT: XPO1/CRM1 is a key nuclear exporter protein that mediates translocation of numerous cellular regulatory proteins. We investigated whether XPO1 is a potential therapeutic target in melanoma using novel selective inhibitors of nuclear export (SINE). In vitro effects of SINE on cell growth and apoptosis were measured by MTS assay and flow cytometry [Annexin V/propidium iodide (PI)], respectively in human metastatic melanoma cell lines. Immunoblot analysis was used to measure nuclear localization of key cellular proteins. The in vivo activity of oral SINE was evaluated in NOD/SCID mice bearing A375 or CHL-1 human melanoma xenografts. SINE compounds induced cytostatic and pro-apoptotic effects in both BRAF wild type and mutant (V600E) cell lines at nanomolar concentrations. The cytostatic and pro-apoptotic effects of XPO1 inhibition were associated with nuclear accumulation of TP53, and CDKN1A induction in the A375 cell line with wild type TP53, while pMAPK accumulated in the nucleus regardless of TP53 status. The orally bioavailable KPT-276 and KPT-330 compounds significantly inhibited growth of A375 (p<0.0001) and CHL-1 (p = 0.0087) human melanoma cell lines in vivo at well tolerated doses. Inhibition of XPO1 using SINE represents a potential therapeutic approach for melanoma across cells with diverse molecular phenotypes by promoting growth inhibition and apoptosis.

21 Article Radiation necrosis mimicking rapid intracranial progression of melanoma metastasis in two patients treated with vemurafenib. 2014

Liebner, David A / Walston, Steven A / Cavaliere, Robert / Powers, Ciaran J / Sauvageau, Eric / Lehman, Norman L / Wayne Slone, Hasel / Xu-Welliver, Meng / Xia, Fen / Kendra, Kari L. ·aDepartment of Internal Medicine, Division of Medical Oncology Departments of bBiomedical Informatics cRadiation Oncology dNeurology eNeurologic Surgery fPathology, The Ohio State University gDepartment of Radiology, Division of Diagnostic Radiology, The Ohio State University, Columbus, Ohio, USA. ·Melanoma Res · Pubmed #24407165.

ABSTRACT: Optimal treatment of metastases to the central nervous system (CNS) in patients with malignant melanoma remains a clinical challenge. In particular, for patients with BRAF-mutant melanoma and CNS metastases, much remains unknown about the safety and efficacy of the novel BRAF-targeted agents when administered in close sequence with radiation. We report two cases of rapid development of CNS radiation necrosis in patients with metastatic melanoma treated with the BRAF inhibitor, vemurafenib, closely sequenced with stereotactic radiosurgery or fractionated stereotactic radiation therapy. In the absence of prospective safety data from clinical trials, we advise vigilance in monitoring patients with BRAF-mutant melanoma whose treatment plan includes CNS radiation and vemurafenib and caution when assessing treatment response within the CNS in these patients.

22 Article Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma. 2011

Thavendiranathan, P / Verhaert, D / Kendra, K L / Raman, S V. ·Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA. ·Br J Radiol · Pubmed #21511746.

ABSTRACT: High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T(2) weighted imaging and T(1) weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T(1) and T(2) weighted CMRI techniques to diagnose IL-2 induced myocarditis.