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Home > Colorectal Cancer |  |
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Supported by an independent educational grant from Roche Laboratories, Inc. |
FacultyEdward Chu, MD (Chairperson)
Yale Cancer Center
Dr. Chu is professor of medicine and pharmacology at the Yale University School of Medicine in New Haven, Connecticut. He received his doctor of medicine from Brown University, where he also completed his residency training in internal medicine. Dr. Chu's research focuses on the design and development of novel treatments for colorectal and other cancers. His studies have provided insights into how tumors become resistant to the effects of chemotherapy. Dr. Chu is the founding editor-in-chief of the journal Clinical Colorectal Cancer. Edward Chu, MD, reported a financial interest/relationship or affiliation in the form of: Consultant, Roche Laboratories, Bristol-Myers Squibb Company and ImClone Systems Inc., and Pfizer Inc. Joel Randolph Hecht, MD
University of California, Los Angeles
Dr. Hecht is clinical professor of medicine at the University of California, Los Angeles (UCLA) and director of the UCLA Gastrointestinal Oncology Program. He received his doctor of medicine from Eastern Virginia Medical School in Norfolk, followed by an internal medicine residency at Northwestern University in Chicago, and fellowships in gastroenterology at the University of Chicago, and gastroenterology and medical oncology at UCLA. Dr. Hecht is board certified in internal medicine, gastroenterology, and medical oncology. His research includes preclinical models of therapy with biological agents, early studies with gene therapy vectors and tyrosine kinase inhibitors, and phase II and III trials with novel agents. Joel Randolph Hecht, MD, reported a financial interest/relationship or affiliation in the form of: Consultant, Takeda Pharmaceuticals Inc., Pfizer Inc., GlaxoSmithKline plc, AstraZeneca plc, and ImClone Systems Inc. New Clinical Questions: Adjuvant TherapyMost patients with colorectal cancer are treated surgically, but a large fraction relapse and die. The advent of adjuvant chemotherapy has significantly advanced the care of these patients, curing thousands each year. TNM staging has identified stage III (lymph node-positive) patients as having a significant risk of relapse, and further studies have demonstrated increased survival in this population with 5-fluorouracil (FU)–based therapy. Stage II (T3–4, N0) patients have a lesser, but nontrivial, chance of relapse, yet the role of adjuvant therapy remains unclear. Previous studies demonstrated a small increase in overall survival with 5-FU–based therapies, although pooled analyses revealed a 4% improvement. Recently, the randomized QUASAR trial reported a 3.6% improvement in overall survival that was statistically significant. Current therapies help 1 out of every 28 patients treated. This has created a need for the investigation of alternative treatment/diagnostic strategies for stage II patients, including the identification of markers indicative of higher risk of recurrence and improved benefit with therapy. The MOSAIC trial, which compared FOLFOX to 5-FU, showed no difference in the survival of the overall population of patients with stage II disease, but did demonstrate a significant increase in the survival of patients clinically determined to be high risk. In particular, findings showed that the number of lymph nodes sampled was an important prognostic factor, and new quality guidelines now recommend that at least 12 lymph nodes be identified and examined. Newer methods of detecting lymph nodes or genetic markers are under investigation in ongoing studies. Further advances in molecular biology may identify additional markers or sets of markers that can be used as effective prognostic tools. Heinz-Josef Lenz, MD
Norris Comprehensive Cancer Center/University of Southern California
Dr. Lenz is professor of medicine at Norris Comprehensive Cancer Center at the University of Southern California in Los Angeles. He received his doctor of medicine from the University of Vienna. His National Cancer Institute-funded research includes the investigation of gene expression regulation associated with drug-resistance, early detection of colorectal cancer, and improved surveillance methods. He has written a multitude of peer-reviewed articles on these and other gastrointestinal cancer-related topics. Dr. Lenz is the recipient of numerous awards including the American Society of Clinical Oncology (ASCO) Young Investigator Award, the ASCO Career Development Award, and the STOP CANCER Career Development Award. Heinz-Josef Lenz, MD, reported a financial interest/relationship or affiliation in the form of: Grant Support, National Cancer Institute and National Institutes of Health, Cancer Therapy Evolution Program, and Southwest Oncology Group; Consultant, Response Genetics, Genentech BioOncology, Amgen Inc., Merck KG, Novartis AG, sanofi-aventis U.S. Inc., Pfizer Inc., and Bristol-Myers Squibb Company and ImClone Systems Inc.; Speaker’s Bureau, Roche Laboratories, Pfizer Inc., Eli Lilly and Company, sanofi-aventis U.S. Inc., and Merck KG; Contracted Research, Bristol-Myers Squibb Company, Celmed BioSciences, Novartis AG, Roche Laboratories, sanofi-aventis U.S. Inc., Genentech BioOncology, Eisai Inc., Taiho Pharmaceutical Co., Ltd., Pfizer Inc., National Cancer Institute, Cancer Therapy Evolution Program, Merck KG, American Academy of Clinical Psychiatrists, Inc.; Clinical Trials, Roche Laboratories, Bristol-Myers Squibb Company and ImClone Systems Inc., Eli Lilly and Company, Novartis AG, sanofi-aventis U.S. Inc., Genentech BioOncology, Pfizer Inc., AstraZeneca plc. New Clinical Questions: Liver-Limited DiseaseHepatic resection is the only potentially curative option for the treatment of liver metastases. Unfortunately, 80% of patients with metastatic disease are considered unresectable at presentation. Five-year survival rates following resection range from 25% to 40% in most large series. The benefits of neoadjuvant and adjuvant chemotherapy for the treatment of liver-only metastases are increasingly appreciated. Chemotherapeutic agents, including oxaliplatin and irinotecan, capable of inducing significant tumor shrinkage and prolonging survival in nonoperable disease also appear to allow an additional 10% to 20% of patients initially thought to be unresectable to undergo metastectomy. Long-term survival rates for these patients previously treated with palliative intent alone are comparable to those of primarily resected patients. As a result, definitions of surgical resectability of liver metastases are constantly evolving. Key contemporary developments in surgical technique, radiographic imaging, and chemotherapy are leading the treatment of colorectal liver metastases to a new multidisciplinary level, involving surgical, medical, and radiologic subspecialties.
Eric Van Cutsem, MD, PhD
University of Leuven, Belgium
Dr. Van Cutsem is professor of internal medicine at the University of Leuven in Belgium. He received his doctor of medicine with a specialization in internal medicine from the University of Leuven. He has written more than 200 peer-reviewed articles on gastrointestinal (GI) cancers. His articles have been published in journals such as The New England Journal of Medicine, Lancet, and Journal of Clinical Oncology. He coordinates several international clinical trials investigating new drugs for the treatment of GI cancers. Dr. Van Cutsem also serves on numerous GI cancer steering committees and advisory boards as well as the editorial board of journals including Journal of Clinical Oncology, Annals of Oncology, and Clinical Colorectal Cancer. Eric Van Cutsem, MD, PhD, reported a financial interest/relationship or affiliation in the form of: Contracted Research, Roche Laboratories, sanofi-aventis U.S. Inc., Pfizer Inc., and Merck Serono International S.A. New Clinical Questions: Metastatic DiseaseStrategies for the management of patients with metastatic colorectal cancer (MCRC) have advanced dramatically during the past several years, as survival rates continue to increase. The development of new cytotoxic agents (e.g., irinotecan, oxaliplatin, capecitabine) and targeted therapies (e.g., bevacizumab, cetuximab, panitumumab) and the multidisciplinary management of patients with resectable and initially nonresectable metastases have contributed greatly to improved treatment outcomes. The efficacy of bevacizumab in the first-line setting has been demonstrated in randomized phase III trials combining bevacizumab with irinotecan and bolus 5-fluorouracil/leucovorin (FU/LV). Moreover, results from randomized phase II studies indicate that bevacizumab increases the activity of 5-FU/LV in the first-line setting. A recent randomized phase III study in the first-line setting showed that capecitabine is as effective as intravenous 5-FU/LV when combined with oxaliplatin and that bevacizumab increases progression-free survival (PFS) associated with fluoropyrimidine/oxaliplatin treatment. In the second-line setting, combination therapy with bevacizumab and FOLFOX has been shown to increase median survival, PFS, and response rates compared to FOLFOX alone. Cetuximab and panitumumab are active in epidermal growth factor receptor (EGFR)-expressing irinotecanrefractory MCRC. The combination of cetuximab and irinotecan has been shown to be more effective in this setting compared to cetuximab alone. Recent data have demonstrated increased PFS in response to treatment with cetuximab plus chemotherapy in less advanced stages of MCRC. In the first-line setting, PFS has been shown to be significantly longer when patients receive FOLFIRI and cetuximab compared to FOLFIRI alone. Similar results have been shown when patients receive cetuximab and irinotecan compared to irinotecan alone in the second-line setting. Questions and challenges remain regarding the optimal use of targeted therapies in the treatment of MCRC. How can we further enhance patient outcomes? A crucial step will be the identification of patient populations that will be more likely to respond to bevacizumab-containing regimens and also to the anti-EGFR antibodies cetuximab and panitumumab. Another challenge is the determination of the best combinations and sequences of administration of cytotoxic agents and biologicals in the treatment of MCRC. To this end, it is imperative that we gain an understanding of the mechanism(s) underlying the shift from therapy-responsive to therapyresistant disease.
Bruce D. Minsky, MD
Pritzker School of Medicine, University of Chicago
Dr. Minsky is associate dean and professor of radiation and cellular oncology at the Pritzker School of Medicine at the University of Chicago. He received his doctor of medicine from the University of Massachusetts, followed by an internship in radiation therapy at New England Deaconess Hospital, in Boston. He completed his residency training in radiation therapy at Harvard Joint Center for Radiation Therapy, also in Boston. Dr. Minsky is on the editorial board of several journals and recently served on the board of directors of the American Society of Clinical Oncology and the American Society for Therapeutic Radiation and Oncology. He has written or cowritten more than 350 journal articles, book chapters, editorials, and abstracts in the field of gastrointestinal oncology. Bruce D. Minsky, MD, reported a financial interest/relationship or affiliation in the form of: Consultant, sanofi-aventis U.S. Inc., Genentech BioOncology, Bristol-Myers Squibb Company; Speaker’s Bureau, sanofi-aventis U.S. Inc., Genentech BioOncology, Bristol-Myers Squibb Company. New Clinical Questions: Locally Advanced Rectal CancerConventional treatment for patients with clinical locally advanced (uT3/4 or N+) rectal cancer involves a multimodality approach combining preoperative interventions with postoperative therapy. In general, continuous infusional 5-fluorouracil (5-FU) or capecitabine is combined with 50.4 Gy radiation therapy prior to total mesorectal exision (TME); this is followed by 4 months of postoperative systemic chemotherapy. Novel combinations of cytotoxic agents (e.g., capecitabine, oxaliplatin, irinotecan) and targeted therapies (e.g., bevacizumab, cetuximab) that have demonstrated efficacy in the adjuvant and/or metastatic setting(s) are being evaluated in the locally advanced setting in phase I/II trials. Recent findings suggest that these approaches achieve superior pathological complete response rates. However, in some cases, there is a concomitant increase in acute toxicities. Phase III trials are therefore needed to determine whether these novel multimodality approaches offer an advantage compared with conventional 5-FU–based treatment. Privacy PolicyWhen you participate in a CME activity provided by the Postgraduate Institute for Medicine (“PIM” or “we”), we ask you for your name, degree, affiliation, street address, telephone number, fax number, and e-mail address (the “Information”). 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