DEPARTMENT OF ONCOLOGY REPORT 2003
DIVISION OF MEDICAL ONCOLOGY –DR. VIVIEN H.C. BRAMWELL, DIVISION CHIEF
INTRODUCTION
The Division of Medical Oncology undertakes scholarly activity and provides clinical care across the whole spectrum of Tumor Groups (see Clinical Service). The majority of members have full-time academic appointments in the Department of Oncology, University of Calgary. The specialty is advancing rapidly in terms of availability of multiple treatments, complexity of those treatments and range of conditions now treatable. Much of the evidence supporting recommendations for new systemic therapies is derived from large-scale, multicentre phase III trials, and members of the Division are both leaders and contributors in this research activity. The role of the Medical Oncologist is changing and time demands on medical staff are rising inexorably as patients tend to be much sicker; they are also better informed and increasingly wish to partner with their Oncologist in formulating treatment plans.
Dr. Bramwell assumed leadership of the Division on January 1st, 2003. A graduate of our Residency Training Program, Dr. Tina Cheng, joined on April 1st, 2003. Departures were Dr. Edna Rapp, who retired March 31st; Dr. Scott Ernst, who joined London Regional Cancer Centre, Ontario, in July; and Dr. Stefan Glück who moved in October, to the University of Miami.
To chart the Division’s future course in this changing climate, a full-day Retreat was held on March 21st, 2003, entitled “Research to Practice: Barriers to Excellence”. We developed a vision for Medical Oncology that; “Within ten years, TBCC becomes known as the premier centre in Canada for the development and delivery of effective research-based clinical care”. Team effort by members of the Division, with different but important contributions across the spectrum of clinical practice, research, education and administration, is moving us in the direction of our vision.
EDUCATION
Drs. Cindy Card and Scot Dowden are each in the second year of study for a Master’s Degree in Education. Despite significant clinical workloads, each have completed most of their required courses and are starting work on their theses. Dr. Card is taking on increasing responsibilities as a lecturer, preceptor and examiner within the Undergraduate Education Program and is Co-Chair of the Department of Oncology Continuing Medical Education Committee. Dr. Dowden is coordinator for several aspects of the Medical Oncology Training Program, and is developing a web-based Continuing Medical Education Program in Oncology.
Dr. Don Morris, as chair of the Postgraduate Education Committee, steered all the Oncology Residency Programs, including Medical Oncology, through a successful review by the Royal College of Physicians and Surgeons of Canada. Three Medical Oncology trainees, Drs.JohnSarantopoulos, Sasha Lupichuk and Margaret Balcewicz, completed their Medical Oncology training in 2003. All have gone on to undertake research fellowships elsewhere in Canada or the US. Dr. Sasha Lupichuk will be returning in September 2004, having completed a one-year Genetics Fellowship at McMaster University in Hamilton, with a plan to complete a Master’s Degree in Epidemiology. Dr. Laura Chow entered the second year of her two-year program, and we welcome Drs. Wei Lin, Patricia Tang and Marc Webster to the first year of our Medical Oncology Fellowship Program. We continue to teach Residents from Internal Medicine, Neurology and the other Oncology disciplines who rotate through Medical Oncology.
Dr. Peter Forsyth supervised three PhD students, Tommy Alain, Angela McDermid and StephenHanson, as well as four Postdoctoral Fellows, Drs. Wenqing Yang, Donna Senger, Xueqing Lun and Bo Huang, working in the Brain Tumor Laboratory Program. Dr. Don Morris supervised two Postdoctoral Fellows, Drs. Chandini Thirukkumaran and Angus Kim, working in his Translational Research Program.
Dr. Desirée Hao was a member of the American Society of Clinical Oncology Career Development Committee, and served as a liaison to the Cancer Communications Committee. She has now become a full member of the latter committee, which oversees public and media relations for the Society. Dr. Doug Stewart completes a 3-year term as Chair of the Examination Board for Medical Oncology, Royal College of Physicians and Surgeons of Canada.
RESEARCH
Translational
Dr. Peter Forsyth’s innovative laboratory and clinical work with reoviruses continues, supported by multiple grants from Alberta Cancer Board (ACB), National Cancer Institute of Canada (NCIC), Canadian Institutes of Health Research (CIHR) and Industry. Phase I and II studies in recurrent malignant gliomas are currently under way. The Brain Tumor Program has been considerably strengthened by recruitment of Dr. Greg Cairncross into the ACF Chair in Neuro-Oncology. Dr.Don Morris maintains a program of laboratory and clinical research into reoviruses, apoptotic pathways in breast and prostate cancer, and graft engineering with stem cell purging techniques, grant funded by ACB, NCIC, Prostate Cancer Research Foundation and Industry. Dr. Vivien Bramwell continues a longstanding collaboration with Dr. Ann Chambers, Canada Research Chair at the University of Western Ontario, to undertake laboratory and clinical studies of osteopontin in breast cancer. This work is supported by grants from Canadian Breast Cancer Research Initiative and the Canadian Breast Cancer Foundation.
Clinical Research
During 2003, Medical Oncologists contributed 290 patients to more than 50 clinical trials. A further 177 patients were recruited into bone marrow transplant protocols. In addition, 51 patients received two promising investigational drugs, Iressa and Alimta, through compassionate release programs. Samples and clinical data from 51 individuals were submitted to the Brain Tumor Bank.
Dr. Vivien Bramwell has been Chair of the Canadian Sarcoma Group/NCIC Clinical Trials Group (NCIC-CTG) Sarcoma Committee for the past eighteen years. In this capacity, she participated in the 5-year grant renewal process for the Clinical Trials Group, was involved in the establishment of a US/Canada Sarcoma Intergroup and was part of a 25-member Progress Review Group in Sarcoma, sponsored by the National Cancer Institute in the US. She is also the Canadian Principal Investigator for an Intergroup sarcoma adjuvant trial, NCIC-CTG SR3/EORTC 62931, and is on the Trial Committee for the Canadian-led International breast cancer adjuvant trial, NCIC-CTG MA-21. Dr. Sandy Paterson is a leading Canadian Investigator in the National Surgical Adjuvant Breast Project (NSABP) and is currently on their Board of Directors. He is the Principal Investigator for a large International phase III breast cancer adjuvant trial, B-34. Dr. Barbara Walley is a North-American Intergroup Chair for the International Breast Cancer Study Group (IBCSG) trial, 25-02, and is the Canadian Principal Investigator for two related IBCSG breast cancer adjuvant trials.
Clinical Service
Tumor Group assignments are as follows:
Vivien Bramwell-Breast Cancer, Sarcoma
Cynthia Card-Lung Cancer
Tina Cheng-Genitourinary Cancer, Melanoma
Scot Dowden-Gastrointestinal Cancer
Peter Forsyth-Brain Cancer
Desirée Hao-Lung Cancer, Head and Neck Cancer
Don Morris-Lung Cancer, Sarcoma
Sandy Paterson-Breast Cancer, Neuroendocrine Tumors
Dean Ruether-Genitourinary Cancer, Breast Cancer, Hematological Malignancies
James Russell-Allogeneic & Autologous Stem Cell/Bone Marrow Transplantation
Doug Stewart-Breast Cancer, Lymphoma, Bone Marrow Transplantation
Barbara Walley-Breast Cancer, Gastrointestinal Cancer
Alfred Wong-Gastrointestinal Cancer
Medical Oncologists provided leadership to four Tumor Groups – Breast (Dr. S. Glück), Lymphoma (Dr. D. Stewart), Neurology (Dr. P. Forsyth) and Bone Marrow Transplant (Dr. J. Russell). The Medical Oncologists are assisted by Drs. Ahsan Chaudhry and Oluyemi Jeje, who are Ward Physicians for the Bone Marrow Transplant Program and Medical/Radiation Oncology; Dr. Heather Hicks who continues as a full-time GP Oncologist; and a number of Clinical Associates (Drs. Tara Pickering, Danelle Hames, Pat Heard, Bryan Brunet, Annie Claude, Alison Murray, Leslie Coulter and Ardythe Taylor) provide support on a sessional basis.
The Division of Medical Oncology saw approximately 2500 new consultations in 2003, mainly from within Southern Alberta, but including some referrals from British Columbia and Saskatchewan. Approximately 10,000 patients made 38,000 visits to the Medical Day Care Unit to receive chemotherapy and supportive care (blood transfusions, bisphosphonates, etc.) during 2003. Although the majority of these patients are under the care of Medical Oncologists, Hematologists and Gynecological Oncologists also use the facilities.
Particular thanks are due to Dr. Dean Ruether, our busiest clinician, who has a broad-based practice which includes monthly clinics in Medicine Hat. He was a great assistance to the Division, following the departure of Dr. Scott Ernst, in agreeing to change the focus of his practice to take a leadership role in clinical research and patient care for the very busy Genitourinary Tumor Group. With the departure of Dr. John Jensen from the Medicine Hat Associate Cancer Centre, Dr. Tina Cheng stepped in for six months, spending two days a week in Medicine Hat performing consultations and overseeing chemotherapy. Dr. Alfred Wong maintains a busy practice in gastrointestinal cancer.
SUMMARY
2003 has been a busy and academically productive year for the Division of Medical Oncology. Despite significant clinical demands, members of the Division have made diverse contributions in undergraduate and postgraduate education, translational and clinical research, and research leadership.
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PEER REVIEWED MANUSCRIPTS PUBLISHED IN 2003
Ernest C Borden, Lawrence H Baker, Robert S Bell, Vivien Bramwell, George D Demetri, Burton L Eisenberg, Christopher DM Fletcher, Jonathan A Fletcher, Marc Landeyni, Paul Meltzer, Brian O’Sullivan, David R Parkinson, Peter WT Pisters, Scott Saxman, Samuel Singer, Murali Sundaram, Allan T Van Oosterom, Jaáp Verweij, Jill Waalen, Sharon W Weiss, Murray F Brennan. Soft tissue sarcomas of adults: state of the translational science. Clinical Cancer Research 9:1941-1956, 2003.
Elaine S Bouttell, N Wilson Rodger, Vivien HC Bramwell. Metastatic secondary fibrosarcoma of bone responsive to repeated courses of ifosfamide and associated with hypoglycemia. Sarcoma 7:81-85, 2003.
Michael Crump, Dongsheng Tu, Lois Shepherd, Mark Levine, Vivien Bramwell, Kathleen Pritchard. Risk of acute leukaemia following epirubicin-based adjuvant chemotherapy: a report from the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 21:16, 3066-3071, 2003.
George N Naumov, Jason L Townson, Ian C MacDonald, Sylvia M Wilson, Vivien HC Bramwell, Alan C Groom, Ann F Chambers. Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Research & Treatment 82:199-206, 2003.
N Iscoe, V Bramwell, M Charette, T Oliver and the Systemic Treatment Disease Site Group. Liposomal antrhacyclines in the management of patients with HIV-positive Kaposi sarcoma. Current Oncology 10(1):17-35, 2003.
Vivien HC Bramwell. Management of advanced adult soft tissue sarcoma. Sarcoma 7:43-45, 2003.
I Quirt, V Bramwell, M Charette, T Oliver and the Cancer Care Ontario Practice Guidelines Initiative Systemic Treatment Disease Site Group. Role of erythropoietin in the management of cancer patients with non-hematologic malignancies receiving chemotherapy. Current Oncology 10(2):84-101, 2003.
C Campbell, V Bramwell, M Charette, T Oliver and the Cancer Care Ontario Practice Guidelines Initiative Systemic Treatment Disease Site Group. Roles of colony-stimulating factor in patients receiving myelosuppressive chemotherapy for treatment of cancer. Current Oncology 10(2)102-126, 2003.
Bramwell VH, Anderson D, Charette ML; Sarcoma Disease Site Group. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma. Cochrane Database Syt Rev. 2003;(3): CDOO3293.
P. Major, A. Figueredo, V. Tandan, V. Bramwell, M. Charette, T. Oliver, and the Systemic Treatment Disease Site Group. Role of octreotide in the management of patients with cancer. Current Oncology 10(3): 161-178, 2003.
Cheng T, Forsyth P, Chaudhry A, Morris D, Glück S, Russell JA and Stewart DA. High dose Thiotepa, Busulfan, Cyclophosphamide and ASCT without whole brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant 2003:31, 679-685.
Townsley C, Chi K, Ernst DS, Belanger K, Tannock I, Bjarnason G, Stewart D, Goel R, Siu L, Jolivet J, McIntosh L, Seymour L, Moore MJ. Troxacitabine, a novel L-nucleoside analog has modest activity in patients with advanced and/or metastatic renal cell carcinoma. J Clin Oncol 21(8): 1524-9, 2003.
Forsyth P, Weaver S, lton D, Brasher PMA, Sutherland G, Stewart D, Hagen, NA, Barnes P, Cairncross JG, DeAngelis LM Difficulties in Answering an Important Question in Neuro-Oncology: Prophylactic Anticonvulsants in Patients With Brain Tumors. The Canadian Journal of Neurological Sciences. 30: 106-112, 2003. (see editorial in same issue by Mason W.P., pg 89-90).
Nuttall Robert K, Pennington Caroline J, Taplin Jennifer, Wheal Alison, Yong V Wee, Forsyth Peter, Edwards Dylan R. Elevated Membrane-Type Matrix Metalloproteinases in Gliomas Revealed by Profiling Proteases and Inhibitors in Human Cancer Cells. Molecular Cancer Research 1: 333-45, 2003.
Yang W, Senger D, Muzik H, Shi ZQ, Johnson D, Brasher PMA, Rewcastle NB, Hamilton M, Rutka J, Wolff J, Wetmore C, Curran T, Lee PWK, Forsyth PA. Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma. Cancer Research 63, 3162-3172, 2003.
Senger D, Cairncross JG, Forsyth PA. Long-term survivors of glioblastoma: statistical aberration or important unrecognized molecular subtype? Cancer J. 2003, 9(3):214-21.
Belanger K, MacDonald D, Cairncross G, Gertler S, Forsyth P, Burdette-Radoux S, Bergeron J, Soulieres D, Ludwin S, Wainman N, Eisenhauer E. A phase II study of topotecan in patients with anaplastic oligodendroglioma or anaplastic mixed oligoastrocytoma. Invest New Drugs. 2003; 21(4):473-80.
Abrey LE, Childs BH, Paleologos N, Kaminer L, Rosenfeld S, Salzman D, Finlay JL, Peterson K, Hu W, Swinnen L, Bayer R, Forsyth P, Stewart D, Smith AM, Macdonald DR, Weaver S, Ramsey DA, DeAngelis LM, Cairncross JG. High Dose Chemotherapy With Stem Cell Rescue as Initial Therapy for Anaplastic Oligodendroglioma. J. Neuro-Oncol 2003, 65(2): 127-134.
Hao D, Hammond LA, Eckhardt SG, et al. A phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor. Clin Cancer Res 9:2465-2471, 2003.
Alain T, Thirukkmaran C, Morris D, Urbanski S, Janowska-Wieczorek A, Lee P, Kossakowska A. Lymphomas and Oncolytic Viral Therapy. Clinical Lymphoma 4(2): 1-8, 2003.
Paterson AHG. Taxanes and Primary Operable Breast Cancer: Should These Agents be Used in Adjuvant Therapy? Oncology Exchange: Vol 2, No 2, (suppl 1) pp20-23, 2003.
Paterson AHG. Bone Metastases: From the Bench to the Bedside: Potential for Prevention. ASCO Educational Book pp 81- 88, 2003.
Atula S, Powles TJ, Paterson AHG, et al. Extended Safety Profile of Oral Clodronate After Long-Term Use in Primary Breast Cancer Patients. Drug Safety 26:9 pp 661-671, 2003.
Thomas F Hack, Tom Pickles, Barry D Bultz, J Dean Ruether, Lorna M Weir, Lesley F Degner, and R Mackey. Impact of Providing Audiotapes of Primary Adjuvant Treatment Consultations to Women With Breast Cancer: A Multisite, Randomized, Controlled Trial. J Clin Oncol 21 (22) 4138-4144, 2003.
Ringden O, Barrett AJ, Zhang M-J, Loberiza FR, Bolwell BJ, Cairo MS, Gale RP, Hale GA, Litzow MR, Martino R, Russell JA, Tiberghien P, Urbano-Ispizua A, Horowitz MM. Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses. Br J Haematol 2003, 121(6):874.
Syme R, Stewart D, Rodriguez-Galvez M, Luider J, Auer Y, Klassen J, Morris D, Brown C, Russell J, Glück S. Micrometastases in apheresis products predict shorter progression-free and overall survival in patients with breast cancer undergoing high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ABSCT). Bone Marrow Transplant 2003;32:307-311.
Thirukkumaran CM, Luider JM, Stewart, DA, Cheng T, Lupichuk SM, Nodwell MJ, Russell JA, Auer IA, Morris DM. Reovirus oncolysis as a novel purging strategy for autologous stem cell transplantation. Blood 2003; 102: 377-387.
Abrey A, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive Methotrexate and Cytarabine Followed by High-dose Chemotherapy with Autologous Stem Cell Rescue in Patients with Newly Diagnosed Primary CNS Lymphoma: An Intent to Treat Analysis. J Clin Oncol 2003; 21: 4151-4156
W Scheithauer, J McKendrick, S Begbie, M Bormer, WI Burns, HA Burris, J Cassidy, D Jodrell, P Koralewski, EL Levine, N Marschner, J Maroun, P Garcia-Alfonso, J Tujakowski, G van Hazen, A Wong, J Zaluski, C Twelves. Oral Capecitabine as an alternative to IV 5-Fluorouracil-based adjuvant therapy for colon cancer: Safety results of a randomized, phase III trial. Annals of Oncology 14:1735-1743, 2003.
PEER REVIEWED ABSTRACTS PUBLISHED IN 2003
RS Benjamin, C Rankin, C Fletcher, C Blanke, M Von Mehren, R Maki, V Bramwell, L Baker, E Borden, GD Demetri for the Sarcoma Intergroup. Phase III dose-randomised study of imatinib mesylate (STI 571) for GIST: Intergroup S0033 early results. Proc. Am. Soc. Clin. Oncol. 22:814, 2003.
Jay S Wunder, Nalan Gokgoz, Sasha Eskandarian, Wenqing He, Shelley B Bull, Anthony Griffin, Soha Riad, Robert E Turcotte, Vivien H Bramwell, Robert S Bell, Rita Kandel, Irene L Andrulis. Towards an improved classification of malignant fibrous histiocytoma. Connective Tissue Oncology Society Annual Meeting 2003, Barcelona, Spain.
Stefan Glück, J MacKinnon, H Lau, R Syme, J Dort, D Glück, University of Calgary. Metronomic therapy in recurrent and metastatic chemo-resistant SCCHN: Data from a pilot study. Proc. Am. Soc. Clin. Oncol. 11:513, 2003.
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J Dancey, M Crump, Stefan Glück, D Tu, S Marlin, L Shepherd, for the NCI Canada Clinical Trials Group. Quality of life (QOL) analysis of a randomized trial of high-dose chemotherapy (HDCT) with peripheral stem cell transplant (PSCT) versus standard chemotherapy (SCT) in women with metastatic breast cancer (MBC): National Cancer Institute of Canada Clinical Trials Group study (NCIC-CTG) MA-16. Proc. Am. Soc. Clin. Oncol. 22:749, 2003.
Glück S. Editorial – Reflection and reaction: Breast cancer trial with erythropoietin terminated unexpectedly. The Lancet Oncology, 2003: 4, 459-460.
Morris D, Forsyth P, Paterson A, Donnelly B, DeFrancesco L, Trpkov K, Coffey M. Reovirus as a Potential Ras Pathway Therapeutic: In Vitro and In Vivo Activity, Tumour Selectivity and Safety. Biotherapy of Cancer from Disease to Targeted Treatment, Munich Germany, September 2003.
James A Russell, Man-Chiu Poon, A Robert Turner, Ahsan M Chaudhry, Ramakrishnan Parameswaran, Diana Quinlan, Oluyemi Jeje, Christopher B Brown, Stefan Glück, Don Morris, Douglas Stewart, Loree M Larratt. GVHD Mortality and Control of Leukemia in Adult Allogeneic BMT Recipients with CML in CP1 Given Daily IV Busulfan, Fludarabine, and Low-Dose Antithymocyte Globulin (ATG): Comparison with Historical Experience Using BuCy2 without ATG. Blood 2003; 102 (11):Abstr 5583.
James A Russell, Ahsan M Chaudhry, Ramakrishnan Parameswaran, Diana M Quinlan, Stefan Glück, Don Morris, Christopher Brown, Douglas A Stewart, Oluyemi Jeje, Loree M Larratt, A Robert Turner. Outcomes of 100 Adult Matched Sibling Stem Cell Transplant (SCT) Recipients Given Pretransplant Low-Dose Antithymocyte Globulin (ATG) and Followed for at Least One Year. Blood 2003; 102 (11): Abstr 1734.