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Tx 60 yo w/ liver mets, questionable resectablility, 18 mo after adj FOLFOX?

What treatment approach would you most likely recommend for a 60-year-old patient with KRAS wt colon cancer who presents 18 months after adjuvant FOLFOX with 4 bilateral liver lesions that are questionable in terms of resectability but may be operable if a response is achieved?

Steven R Alberts, MD, MPH
Chair, Division of Medical Oncology
Professor of Oncology
Mayo Clinic
Rochester, Minnesota
Answer: FOLFIRI + cetuximab

This is a patient for whom I would use FOLFIRI and cetuximab to achieve resectable disease. If the patient experienced a response prior to surgery or achieved stable disease, I would treat postoperatively to complete 12 cycles altogether, including whatever was administered prior to surgery.

Al B Benson III, MD
Professor of Medicine
Associate Director for
Clinical Investigations
Robert H Lurie Comprehensive
Cancer Center of
Northwestern University
Chicago, Illinois
Answer: FOLFOXIRI + bev

I would be more likely to switch to a different chemotherapy regimen and use FOLFOXIRI with this patient. Because the disease is KRAS wt and the patient needs a response, I would add bevacizumab. However, the use of FOLFIRI would still be part of the discussion, and I would even be comfortable using FOLFOX in this 60-year-old patient.

Charles S Fuchs, MD, MPH
Director
Center for Gastrointestinal Cancer
Dana-Farber/Harvard Cancer Center
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Answer: FOLFIRI + bev

Although both FOLFOX/bevacizumab and FOLFIRI/bevacizumab are reasonable options in the setting of a greater than 12-month disease-free interval, FOLFIRI/bevacizumab is a reasonable option as first-line treatment and provides a therapy that is different from the adjuvant regimen.

Richard M Goldberg, MD
Professor of Medicine
Physician-in-Chief, OSUCCC -
James Cancer Hospital and
Richard J Solove Research Institute
Klotz Family Chair in Cancer Research
The Ohio State University
Columbus, Ohio
Answer: FOLFIRI + bev

I would treat with FOLFIRI/bevacizumab. In this situation, I generally do not offer further treatment postoperatively but would observe the patient. We do not have data indicating that FOLFIRI-based regimens help in the adjuvant setting. However, the patient received FOLFOX before, and that didn’t cure the disease.

Axel Grothey, MD
Professor of Oncology
Department of Medical Oncology
Mayo Clinic
Rochester, Minnesota
Answer: FOLFIRI + bev

My answer has changed since ASCO 2013. Before ASCO, I would have chosen FOLFIRI and an EGFR antibody. After the data from the new EPOC study were presented at ASCO 2013, I would not recommend an EGFR antibody in this setting because the study showed a detrimental effect if cetuximab was added to chemotherapy for patients with KRAS wt disease and operable liver metastases. So my choice in this scenario is FOLFIRI and bevacizumab.

If I see a response, the question of whether to offer postoperative therapy can be uncertain because we have some data on oxaliplatin-based therapy and irinotecan-based therapy but they’re not strong. Having said that, if I saw a strong response in these lesions I would even consider using FOLFIRI postoperatively, but I would not use bevacizumab postoperatively.

Howard S Hochster, MD
Associate Director (Clinical Research)
Yale Cancer Center
Professor of Medicine
Yale School of Medicine
New Haven, Connecticut
Answer: FOLFOXIRI + bev

We would use FOLFOXIRI with bevacizumab for 3 months prior to surgery. I would continue treatment for 3 months postoperatively if a complete resection were achieved.

Herbert I Hurwitz, MD
Associate Professor of Medicine
Division of Hematology/Oncology
Clinical Director, Phase I Program
Co-leader, GI Oncology Program
Duke University Medical Center
Durham, North Carolina
Answer: FOLFOXIRI or FOLFOX, CAPOX, or FOLFIRI + biologic

I don’t believe any particular regimen is much more effective if resection is the goal. However, in a patient with borderline resectable disease, the fluoropyrimidine options are not advisable. I would prefer to administer FOLFOXIRI or one of FOLFOX, CAPOX or FOLFIRI with the addition of a biologic agent.

Wells A Messersmith, MD
Professor and Director
GI Medical Oncology Program
Co-Leader
Developmental Therapeutics Program
University of Colorado Cancer Center
Aurora, Colorado
Answer: FOLFIRI + cetuxinab or FOLFOXIRI

Because we are going for a response and trying to achieve resectability, I would either use FOLFIRI with cetuximab or FOLFOXIRI. For a patient who had received 6 months of FOLFOX, I would make sure that liver damage is not a concern. That would argue against FOLFOXIRI because of the chemotherapy-associated steatohepatitis. Postoperatively I don’t tend to use adjuvant EGFR antibody therapy because the data are negative in terms of its benefit to patients. I tend to use a model of 3 months before and 3 months after as was used in the EORTC-40983 trial.