• Researcher Profile

    Matthew H. Kulke, MD

     
    Matthew H. Kulke, MD

    Top Doctor

     
    Director, Program in Neuroendocrine and Carcinoid Tumors

    Associate Professor of Medicine, Harvard Medical School

    Center/Program

    Gastrointestinal Cancer

    Office phone: 617-632-5136
    Fax: 617-632-5370
    Website: Program in Neuroendocrine and Carcinoid Tumors

    Preferred contact method: appointment phone

    View Physician Profile
     
     

    Research Department

    Medical Oncology/Solid Tumor Oncology

    Interests

    Gastrointestinal cancers, Neuroendocrine tumors

    Area of Research

    Gastrointestinal Malignancies and Neuroendocrine Tumors

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 1220
    Boston, MA 02215

    Biography

    Matthew Kulke joined the staff of Dana-Farber Cancer Institute in 1997 and is currently an Associate Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute.

    He received an M.D. from the University of California, San Francisco School of Medicine in 1992. He subsequently completed an internship and residency in internal medicine at Brigham and Women's Hospital, a fellowship in medical oncology at Dana-Farber, and received a masters degree in medical science from Harvard Medical School.

    Dr. Kulke has led numerous clinical and translational studies in patients with gastrointestinal malignancies and neuroendocrine tumors. He has served as study chair for a national study of pancreatic cancer therapies performed by the Cancer and Leukemia group B and funded by the National Cancer Institute.

    His current efforts have focused on clinical and translational research in carcinoid and pancreatic neuroendocrine tumors.

    Dr. Kulke is the recipient of the George Canellos Award for Clinical Investigation and the Ruth Brufsky Award for Pancreatic Cancer Research. He serves on the advisory board for the European Neuroendocrine Tumor Society, the executive committee of the North American Neuroendocrine Tumor Society, and is chair of the Neuroendocrine Tumor Task force for the National Cancer Institute.

    Recent Awards

    • Ruth Brufsky Award for Excellence in Clinical Research on Pancreatic Cancer, University of Pittsburgh School of Medicine, 2009
    • George Canellos Award for Contributions to Clinical Research, Dana-Farber Cancer Institute, 2003
    • Discovery Fellowship, Dana-Farber Cancer Institute, 1999-2001
    • Young Investigator Award, American Society of Clinical Oncology, 1998-1999

    Research

    Gastrointestinal Malignancies and Neuroendocrine Tumors

    We have established a robust clinical and translational research program at Dana-Farber Cancer Institute, focused on neuroendocrine tumors. As part of our clinical research program, we evaluate over 200 neuroendocrine tumor patients annually and have studied numerous novel therapies for neuroendocrine tumor patients.

    Our research has included early studies demonstrating activity of the small molecule tyrosine kinase inhibitor sunitinib and the oral alkylating agent temozolomide in patients with neuroendocrine tumors. We are currently evaluating novel combinations of therapeutic agents in neuroendocrine tumors, including regimens of temozolomide/everolimus and pasireotide/everolimus.

    The temozolomide/everolimus combination will be further evaluated and compared to bevacizumab/everolimus or everolimus alone in a planned cooperative group trial, under the auspices of the Cancer and Leukemia Group B.

    The foundation of our translational research efforts in neuroendocrine tumors is a database of clinical information and biospecimens collected prospectively from over 900 neuroendocrine tumor patients, beginning in 2003. We have used this resource to identify predictive and prognostic factors in patients undergoing treatment for neuroendocrine tumors.

    In recent studies, we have identified alkaline phosphatase as a prognostic marker in patients with advanced neuroendocrine tumors. We have also been able to utilize our biospecimen collection to demonstrate loss of the DNA repair enzyme MGMT in pancreatic neuroendocrine tumors, and to correlate MGMT loss with response to temozolomide-based regimens.

    The rapid development of genomic technology has created several new opportunities to better understand the genetic underpinnings of neuroendocrine tumors. Using single nucleotide polymorphism arrays, we confirmed loss of chromosome 18 as a common event in small bowel carcinoid tumors, and identified recurrent amplifications on chromosome 14 in the vicinity of the anti-apoptosis gene DAD1.

    We are now performing studies evaluating the effect of genetic variation in DAD1 and other candidate genes on neuroendocrine tumor risk and outcome.

    Select Publications

    • Krueger J, Kulke M, Schutt C, Stock J. Protein inclusion body formation and purification.
      Biopharm. 1989: pp. 40-45.
    • Kulke M, Vance E. Pneumocystis carinii pneumonia in patients receiving chemotherapy for
      breast cancer. Clin Infect Dis. 1997;25(2):215-8.
    • Kulke MH, Odze RD, Thakore KS, Thomas G, Wang H, Loda M, Eng C. Allelic loss of 10q23, the PTEN tumour suppressor gene locus, in Barrett's oesophagus-associated adenocarcinoma. Br J Cancer. 2001;84(6):748-53.
    • Kulke MH, Thakore KS, Thomas G, Wang H, Loda M, Eng C, Odze RD. Microsatellite
      instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma.
      Cancer. 2001;91(8):1451-7.
    • Ellis FH, Xu X, Kulke MH, LoCicero J, Loda M. Malignant transformation of the esophageal
      mucosa is enhanced in p27 knockout mice. J Thorac Cardiovasc Surg. 2001;122(4):809-14.
    • Ryan DP, Kulke MH, Fuchs CS, Grossbard ML, Grossman SR, Morgan JA, Earle CC,
      Shivdasani R, Kim H, Mayer RJ, Clark JW. A Phase II study of gemcitabine and docetaxel in
      patients with metastatic pancreatic carcinoma. Cancer. 2002;94(1):97-103.
    • Fuchs CS, Clark JW, Ryan DP, Kulke MH, Kim H, Earle CC, Vincitore M, Mayer RJ, Stuart KE. A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer. 2002;94(12):3186-91.
    • Kulke MH, Demetri GD, Sharpless NE, Ryan DP, Shivdasani R, Clark JS, Spiegelman BM, Kim H, Mayer RJ, Fuchs CS. A phase II study of troglitazone, an activator of the PPARgamma receptor, in patients with chemotherapy-resistant metastatic colorectal cancer. Cancer J. 2002;8 (5):395-9.
    • Ryan DP, Clark JW, Kulke MH, Fuchs CS, Earle CC, Enzinger PC, Stuart K, Catarius KJ, Winkelmann J, Mayer RJ. A phase II study of modified deGramont 5-fluorouracil, leucovorin, and oxaliplatin in previously treated patients with metastatic colorectal cancer. Cancer Invest. 2003;21(4):505-11.
    • Kulke MH, Kim H, Stuart K, Clark JW, Ryan DP, Vincitore M, Mayer RJ, Fuchs CS. A phase II study of docetaxel in patients with metastatic carcinoid tumors. Cancer Invest. 2004;2(3):353-9.
    • Kulke MH, Odze RD, Mueller JD, Wang H, Redston M, Bertagnolli MM. Prognostic
      significance of vascular endothelial growth factor and cyclooxygenase 2 expression in patients
      receiving preoperative chemoradiation for esophageal cancer. J Thorac Cardiovasc Surg.
      2004;127(6):1579-86.
    • Kulke MH, Kim H, Clark JW, Enzinger PC, Lynch TJ, Morgan JA, Vincitore M, Michelini A, Fuchs CS. A Phase II trial of gemcitabine for metastatic neuroendocrine tumors. Cancer.
      2004;101(5):934-9.
    • McCollum AD, Kulke MH, Ryan DP, Clark JW, Shulman LN, Mayer RJ, Bartel S, Fuchs CS.
      Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine
      tumors. Am J Clin Oncol. 2004;27(5):485-8.
    • Zhu AX, Fuchs CS, Clark JW, Muzikansky A, Taylor K, Sheehan S, Tam K, Yung E, Kulke
      MH, Ryan DP. A phase II study of epirubicin and thalidomide in unresectable or metastatic
      hepatocellular carcinoma. Oncologist. 2005;10(6):392-8.
    • Kulke M. Advances in the treatment of neuroendocrine tumors. Curr Treat Options Oncol. 2005;6(5):397-409.
    • 16. Ogino S, Meyerhardt JA, Cantor M, Brahmandam M, Clark JW, Namgyal C, Kawasaki T, Kinsella K, Michelini AL, Enzinger PC, Kulke MH, Ryan DP, Loda M, Fuchs CS. Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer. Clin Cancer Res. 2005;11(18):6650-6.
    • Meyerhardt JA, Heseltine D, Campos H, Holmes MD, Willett WC, Winer EP, Enzinger PC, Bunnell CA, Kulke MH, Fuchs CS. Assessment of a dietary questionnaire in cancer patients receiving cytotoxic chemotherapy. J Clin Oncol. 2005;23(33):8453-60.
    • Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005;50(12):2218-23.
    • Kulke MH, Stuart K, Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Vincitore M, Michelini A, Fuchs CS. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol. 2006;24(3):401-6.
    • McCollum AD, Wu B, Clark JW, Kulke MH, Enzinger PC, Ryan DP, Earle CC, Michelini A, Fuchs CS. The combination of capecitabine and thalidomide in previously treated, refractory metastatic colorectal cancer. Am J Clin Oncol. 2006;29(1):40-4.
    • Li J, Harris L, Mamon H, Kulke MH, Liu WH, Zhu P, Mike Makrigiorgos G. Whole genome amplification of plasma-circulating DNA enables expanded screening for allelic imbalance in plasma. J Mol Diagn. 2006;8(1):22-30.
    • Li J, Wang F, Mamon H, Kulke MH, Harris L, Maher E, Wang L, Makrigiorgos GM. Antiprimer quenching-based real-time PCR and its application to the analysis of clinical cancer samples. Clin Chem. 2006;52(4):624-33.
    • Meyerhardt JA, Zhu AX, Enzinger PC, Ryan DP, Clark JW, Kulke MH, Earle CC, Vincitore M, Michelini A, Sheehan S, Fuchs CS. Phase II study of capecitabine, oxaliplatin, and erlotinib in previously treated patients with metastastic colorectal cancer. J Clin Oncol. 2006;24(12):1892-7.
    • Kulke MH, Wu B, Clark JW, Enzinger PC, Lynch TJ, Vincitore M, Michelini A, Fuchs CS. A phase II study of doxorubicin, cisplatin, and 5-fluorouracil in patients with advanced adenocarcinoma of the stomach or esophagus. Cancer Invest. 2006;24(3):229-34.
    • Clancy TE, Sengupta TP, Paulus J, Ahmed F, Duh MS, Kulke MH. Alkaline phosphatase predicts survival in patients with metastatic neuroendocrine tumors. Dig Dis Sci. 2006;51 (5):877-84.
    • Kulke MH, Wu B, Ryan DP, Enzinger PC, Zhu AX, Clark JW, Earle CC, Michelini A, Fuchs CS. A phase II trial of irinotecan and cisplatin in patients with metastatic neuroendocrine tumors. Dig Dis Sci. 2006;51(6):1033-8.
    • Kulke MH, Muzikansky A, Clark J, Enzinger PC, Fidias P, Kinsella K, Michelini A, Fuchs CS. A Phase II trial of vinorelbine in patients with advanced gastroesophageal adenocarcinoma. Cancer Invest. 2006;24(4):346-50.
    • Kwak EL, Jankowski J, Thayer SP, Lauwers GY, Brannigan BW, Harris PL, Okimoto RA, Haserlat SM, Driscoll DR, Ferry D, Muir B, Settleman J, Fuchs CS, Kulke MH, Ryan DP, Clark JW, Sgroi DC, Haber DA, Bell DW. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res. 2006;12(14 Pt 1):4283-7.
    • Kulke MH, Bergsland EK, Ryan DP, Enzinger PC, Lynch TJ, Zhu AX, Meyerhardt JA, Heymach JV, Fogler WE, Sidor C, Michelini A, Kinsella K, Venook AP, Fuchs CS. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J Clin Oncol. 2006;24(22):3555-61.
    • Zhu AX, Clark JW, Ryan DP, Meyerhardt JA, Enzinger PC, Earle CC, Fuchs CS, Regan E, Anbe H, Houghton M, Zhang J, Urrea P, Kulke MH. Phase I and pharmacokinetic study of S-1
      administered for 14 days in a 21-day cycle in patients with advanced upper gastrointestinal cancer. Cancer Chemother Pharmacol. 2007;59(3):285-93.
    • 31. Ogino S, Meyerhardt JA, Kawasaki T, Clark JW, Ryan DP, Kulke MH, Enzinger PC, Wolpin BM, Loda M, Fuchs CS. CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Virchows Arch. 2007;450 (5):529-537.
    • Schwarzberg AB, Stover EH, Sengupta T, Michelini A, Vincitore M, Baden LR, Kulke MH. Selective lymphopenia and opportunistic infections in neuroendocrine tumor patients receiving temozolomide. Cancer Invest. 2007;25(4):249-55.
    • Meyerhardt JA, Zhu AX, Stuart K, Ryan DP, Blaszkowsky L, Lehman N, Earle CC, Kulke MH, Bhargava P, Fuchs CS. Phase-II Study of Gemcitabine and Cisplatin in Patients with Metastatic Biliary and Gallbladder Cancer. Dig Dis Sci. 2007;(epub ahead of print).
    • Wang F, Wang L, Briggs C, Sicinska E, Gaston SM, Mamon H, Kulke MH, Zamponi R, Loda M, Maher E, Ogino S, Fuchs CS, Li J, Hader C, Makrigiorgos GM. DNA Degradation Test Predicts Success in Whole-Genome Amplification from Diverse Clinical Samples. J Mol Diagn. 2007;(epub ahead of print).
    • Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS. Capecitabine plus erlotinib in gemcitabinerefractory advanced pancreatic cancer. J Clin Oncol. 2007;25(30):4787-92.
    • Bradbury PA, Heist RS, Kulke MH, Zhou W, Marshall AL, Miller DP, Su L, Park S, Temel J, Fidias P, Sequist L, Lynch TJ, Wain JC, Shepherd FA, Christiani DC, Liu G. A rapid outcomes ascertainment system improves the quality of prognostic and pharmacogenetic outcomes from observational studies. Cancer Epidemiol Biomarkers Prev. 2008;17(1):204-11.
    • Plckinger U, Couvelard A, Falconi M, Sundin A, Salazar R, Christ E, de Herder WW, Gross D, Knapp WH, Knigge UP, Kulke MH, Pape UF, Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated tumour/carcinoma of the
      appendix and goblet cell carcinoma. Neuroendocrinology. 2008;87(1):20-30.
    • Duerr EM, Mizukami Y, Ng A, Xavier RJ, Kikuchi H, Deshpande V, Warshaw AL, Glickman J, Kulke MH, Chung DC. Defining molecular classifications and targets in gastroenteropancreatic
      neuroendocrine tumors through DNA microarray analysis. Endocr Relat Cancer. 2008;15(1):243-56.
    • Kulke MH. Neuroendocrine tumors: is there a standard treatment? Gastrointest Cancer Res. 2008;2(3):152-3.
    • Li J, Wang L, Mamon H, Kulke MH, Berbeco R, Makrigiorgos GM. Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing. Nat
      Med. 2008;14(5):579-84.
    • Kulke MH, Freed E, Chiang DY, Philips J, Zahrieh D, Glickman JN, Shivdasani RA. Highresolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer. 2008;47(7):591-603.
    • Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J, Bergsland E, Stuart K, Tye L, Huang X, Li JZ, Baum CM, Fuchs CS. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol. 2008;26(20):3403-10.
    • Sheehy N, Kulke MH, Van Den Abbeele AD. F-18 FDG PET/CT in the Diagnosis and Management of a Pericardiac Paraganglioma. Clin Nucl Med. 2008;33(8):545-6.
    • Fujiki K, Duerr EM, Kikuchi H, Ng A, Xavier RJ, Mizukami Y, Imamura T, Kulke MH, Chung DC. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology. 2008;135(3):907-16, 916.e1-2.
    • Mamon H, Hader C, Li J, Wang L, Kulke M, Amicarelli G, Shehi E, Adlerstein D, Roper K, Killion L, Hooshmand S, Makrigiorgos GM. Preferential amplification of apoptotic DNA from plasma: potential for enhancing detection of minor DNA alterations in circulating DNA. Clin Chem. 2008;54(9):1582-4.
    • Bracht LK, Wen P, Meyerhardt JA, Kulke MH, Hornick JL, Redston M, Lafrankie DC, Black PM, Kesari S, Norden A, Drappatz J. DNA Repair Enzyme Expression and Differential Response to Temozolomide in a Patient With Both Glioblastoma and Metastatic Pancreatic Neuroendocrine Tumor. J Clin Oncol. 2008.
    • Zhai R, Liu G, Asomaning K, Su L, Kulke MH, Heist RS, Nishioka NS, Lynch TJ, Wain JC, Lin X, Christiani DC. Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure, and esophageal adenocarcinoma risk. Carcinogenesis. 2008.
    • Kulke MH, Hornick JL, Frauenhoffer C, Hooshmand S, Ryan DP, Enzinger PC, Meyerhardt JA, Clark JW, Stuart K, Fuchs CS, Redston MS. O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clin Cancer Res. 2009;15(1):338-45.
    • Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med. 2009;360(2):195-7.
    • Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Earle CC, Kulke MH, Meyerhardt JA, Blaszkowsky LS, Zhu AX, Fidias P, Vincitore MM, Mayer RJ, Fuchs CS. Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer. Ann Oncol. 2009.
    • Liu G, Cescon DW, Zhai R, Zhou W, Kulke MH, Ma C, Xu W, Su L, Asomaning K, Heist RS, Wain JC, Lynch TJ, Christiani DC. p53 Arg72Pro, MDM2 T309G and CCND1 G870A polymorphisms are not associated with susceptibility to esophageal adenocarcinoma. Dis Esophagus. 2009.
    • Bradbury PA, Zhai R, Hopkins J, Kulke MH, Heist RS, Singh S, Zhou W, Ma C, Xu W, Asomaning K, Ter-Minassian M, Wang Z, Su L, Christiani DC, Liu G. Matrix Metalloproteinase 1, 3, and 12 Polymorphisms and Esophageal Adenocarcinoma Risk and Prognosis. Carcinogenesis. 2009.
    • Cescon DW, Bradbury PA, Asomaning K, Hopkins J, Zhai R, Zhou W, Wang Z, Kulke M, Su L, Ma C, Xu W, Marshall AL, Heist RS, Wain JC, Lynch TJ, Christiani DC, Liu G. p53 Arg72Pro and MDM2 T309G polymorphisms, histology, and esophageal cancer prognosis. Clin Cancer Res. 2009;15(9):3103-9.
    • Chan JA, Kulke MH. Progress in the treatment of neuroendocrine tumors. Curr Oncol Rep. 2009;11(3):193-9.
    • Bradbury PA, Kulke MH, Heist RS, Zhou W, Ma C, Xu W, Marshall AL, Zhai R, Hooshmand SM, Asomaning K, Su L, Shepherd FA, Lynch TJ, Wain JC, Christiani DC, Liu G. Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes. Pharmacogenet Genomics. 2009;19(8):613-25.
    • Cheung WY, Zhai R, Kulke MH, Heist RS, Asomaning K, Ma C, Wang Z, Su L, Lanuti M, Tanabe KK, Christiani DC, Liu G. Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk. Carcinogenesis. 2009;30(8)1363-7.
    • Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, Saridaki Z, Georgoulias V, Finkelstein D, Fuchs CS, Kulke MH, Shivdasani RA. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. BR J Cancer. 2009;101(3):465-72.
    • Kulke MD, Scherbl H. Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2009;3(5 Supplement 2):S62-6.
    • Kulke MH, Tempero MA, Niedwiecki D, Hollis DR, Kindler HL, Cusnir M, Enzinger PC, Gorsch SM, Goldberg RM, Mayer RJ. Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, Docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. J Clin Oncol. 2009;27(33):5506-12.
    • Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, ODorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trail. J Clin Oncol. 2010;28(1):69-76.
    • Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gonen M, Jensen RT, Kidd M, Kulke MH, Lloyd RV, Moran C, Moss SF, Oberg K, OToole D, Rindi G, Rober ME, Suster S, Tang LH, Tzen CY, Washington MK, Wiedenmann B, Yao J. Pathology Reporting of Neuroendocrine Tumors: Application of the Delphic Consensus Process to the Development of a Minimum Pathology Data Set. Am J Surg Pathol. 2010.
    • Chan JA, Zhu AX, Stuart K, Bhargava P, Earle CC, Clark JW, Case C, Regan E, Kulke MH. Phase II study of pemetrexed in patients with advanced neuroendocrine tumors. Cancer Chemother Pharmacol. 2010.