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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Metastatic Colorectal Cancer: Scoping Out Multidisciplinary Treatment Strategies


GOAL
To provide oncologists with up-to-date information on the treatment of patients with metastatic colorectal cancer.

TARGET AUDIENCE
This activity is designed for oncologists. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, the participant should be able to:

  • Evaluate treatment options and discuss the role of targeted therapies in advanced
    colorectal cancer.
  • Explain the role of surgical resection and other local ablative therapies for isolated metastatic disease.
  • Discuss the optimal method of integrating chemotherapy and surgical therapy of metastatic disease.
  • Understand the role of downstaging of unresectable metastases with chemotherapy and timing of liver resection.
  • Review the evidence for the use of intra-arterial approaches for liver metastases.
  • Outline issues related to the management of synchronous presentation of primary colorectal cancer and hepatic metastases.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The estimated time to complete this educational activity: 2 hours.
Release date: May 15, 2006.
Expiration date: May 15, 2008.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Bristol-Myers Squibb Company and ImClone Systems Inc.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

Michael A. Choti, MD
Professor of Surgery
Jacob C. Handelsman Chair of Abdominal Surgery
The Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Choti reports receiving honoraria from Genentech, Pfizer Inc, and Sanofi-Aventis.

PARTICIPATING FACULTY

Betsy L. Althaus, PharmD
Senior Pharmacist
UCSF Comprehensive Cancer Center
Assistant Clinical Professor
Department of Clinical Pharmacy
School of Pharmacy, UCSF
San Francisco, California
Dr Althaus reports having no financial or advisory relationships with corporate organizations related to this activity.

Jordan Berlin, MD
Associate Professor of Medicine
Vanderbilt University Department of Medicine
Clinical Director
Gastrointestinal Oncology
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee
Dr Berlin reports receiving grants/research support from Bristol-Myers Squibb Company/ImClone, Genentech, and Pfizer Inc; serving as a consultant for Amgen, Genentech, Pfizer Inc, and Sanofi-Aventis; receiving honoraria from Roche; and receiving other financial or material support from Sanofi-Aventis.

Yuman Fong, MD
Chief, Gastric and Mixed Tumor Service
Murray F. Brennan Chair in Surgery
Department of Surgery
Memorial Sloan-Kettering Cancer Center
New York, New York
Dr Fong reports having no financial or advisory relationships with corporate organizations related to this activity.

Axel Grothey, MD
Senior Associate Consultant
Division of Medical Oncology
Mayo Clinic College of Medicine
Rochester, Minnesota
Dr Grothey reports receiving grants/research support from Sanofi-Aventis; serving as a consultant for Genentech, Roche, and Sanofi-Aventis; and receiving honoraria from Genentech, ImClone, Roche, and Sanofi-Aventis.

Karen E. Kim, MD
Assistant Professor of Clinical Medicine
University of Chicago
Director, Colorectal Cancer Prevention Clinic
Chicago, Illinois
Dr Kim reports receiving grants/research support from Merck and Company and Pharmacia.


Notice: The audience is advised that articles in this CME activity contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Althaus—bevacizumab and cetuximab.
Dr Berlin—oxaliplatin and panitumumab.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Metastatic Colorectal Cancer: Scoping Out Multidisciplinary Treatment Strategies
Michael A. Choti, MD

Colorectal cancer is a common disease in the United States. It is the fourth most common cancer after breast cancer, prostate cancer, and lung cancer, with an incidence of about 150 000 cases per year.1 Colorectal cancer is the second leading cause of cancer deaths in the United States, second only to lung cancer. The mortality rate is approximately 55 000 deaths per year.1

Even with the many advances in colorectal cancer treatment, a significant percentage of patients will develop recurrence and die of their disease. Patients diagnosed with stage I disease have a high cure rate, with 90% to 97% 5-year survival rate.2 Mortality increases for patients with more advanced disease. Many patients will present with intermediate disease, in which the risk of recurrence ranges from 20% to 80%, and approximately 20% of patients present with stage IV disease.2

The liver is the most common site of recurrent or metastatic disease. Therefore, the management of hepatic metastatic disease will form the majority of this discussion. More than 50% of patients with liver metastases are not good candidates for surgery.1 Even for those patients with initially resectable liver metastases, most will go on to recur after liver resection. Effective use of neoadjuvant and adjuvant therapies can improve long-term outcome in these patients. In addition, use of aggressive induction chemotherapy can convert initially unresectable patients to resectable status, potentially increasing the number of patients who can be offered potentially curative therapy.

In the following articles, the authors will focus on chemotherapy for advanced disease, on surgical therapy for liver metastases, and on integrating chemotherapy and surgery. Panel discussions follow each article.

In the first article in this issue, Axel Grothey, MD, reviews the use of chemotherapies in the treatment of colorectal cancer. As Dr Grothey notes, oxaliplatin- or irinotecan-based regimens (eg, FOLFOX [5-fluorouracil, leucovorin, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]) are the most efficacious first-line therapies. He presents data on adding a biologic agent to first-line chemotherapy and the potential this treatment has to augment the efficacy of cytotoxic treatments. He outlines that, currently, FOLFOX or FOLFIRI can be offered as first-line therapy. Dr Grothey further elucidates data on improved patient survival with the use of second- and third-line agents, and the potential the sequential use of these agents has to limit toxicity and impact treatment failure. He also describes the use of medical treatments as palliative approaches (with the goals of prolonging life and maintaining quality of life) and also as curative approaches (with the goal of downsizing initially unresectable metastases followed by metastasectomy to maximize response rates or its adjuvant use in the resectable situation), depending upon patient characteristics.

Yuman Fong, MD, discusses improved survival rates for patients with colorectal hepatic metastases achieved through the use of aggressive treatment techniques, and notes that data show surgical resection improves 5-year survival rates in these patients. He describes strategies for improving outcomes after liver resection. Determining which patients are good surgical candidates is dependant upon a variety of factors, including assessment of level of risk. Stratifying patients according to clinical risk will be of assistance in identifying resectable patients who are candidates for aggressive neoadjuvant and adjuvant therapies. Dr Fong also notes that the use of techniques, such as portal vein embolization, can help increase the percentage of patients who can receive resection. He explores the use of diagnostic tests, such as positron emission tomography, to improve detection of metastatic disease and better identify patients who are surgical candidates. He concludes with a presentation of the current data on the role of ablation in treating liver metastases, and comments on the need for further study to determine the relative efficacy of resection as compared to alternative or combined treatments.

Jordan Berlin, MD, discusses the newer chemotherapy agents and strategies used as adjuvant therapy after resection of liver metastases while pointing to the lack of randomized trials that may suggest the optimal clinical strategy. He reviews the current data on hepatic artery infusion chemotherapy when administered as postoperative adjuvant therapy. Dr Berlin reiterates the high response rates seen with newer chemotherapy regimens, and describes the possibility that the neoadjuvant strategy of reducing previously unresectable liver metastases to resectable size may serve to increase the number of patients with curable metastatic colorectal cancer. He explores the issue of timing for resection, before or after chemotherapy, and emphasizes that these patients, whether resectable or unresectable, should be cared for in a multidisciplinary setting. Dr Berlin concludes with a discussion of the complex process of treating synchronous rectal and liver disease, and the expectation that further studies will help oncologists find effective ways to increase cure rates for those patients who are resectable and to enable more patients who are initially unresectable to become candidates for surgery.

Rounding out this issue of Johns Hopkins Advanced Studies in Medicine are highlights of the case study and panel discussion that concluded the roundtable, which include discussion on various scenarios and controversial issues.

We hope that the articles in this monograph are informative and relevant to your clinical practice and will result in better care and improved outcomes in patients with colorectal cancer.

REFERENCES

1. American Cancer Society. Cancer facts and figures 2002. Available at http://www.cancer.org/downloads/STT/ CancerFacts&Figures2002TM.pdf. Accessed April 13, 2006.
2. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual 6th ed. American Joint Committee on Cancer; 2002.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his/her article and all its contents.

*Professor of Surgery, Jacob C. Handelsman Chair of Abdominal Surgery, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Address correspondence to: Michael A. Choti, MD, Professor of Surgery, Jacob C. Handelsman Chair of Abdominal Surgery, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Halstead 614, 600 North Wolfe Street, Baltimore, MD 21287. E-mail: mchoti@jhmi.edu





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.