The pendulum continues to swing in the treatment of stage II and III colon cancer. Not 5 years ago, our party line was that essentially all patients should receive 6 months of adjuvant FOLFOX (leucovorin, fluorouracil [5-FU], oxaliplatin): patients with stage II or III disease, whether rectal or colon cancer, old or young—treat them all the same. And why not? They were all considered to be the same disease, with the same relative risk reduction. If it were not for the neuropathy, the regimen was well tolerated. Might as well offer it, right?
Then things started to shift. The stage II subsets failed to show survival advantages from the addition of oxaliplatin, but many “thought leaders” still insisted that our patients with high-risk stage II cancers and certainly T4 tumors “needed” oxaliplatin. As data in the elderly population began to emerge, thought leaders claimed that we should only avoid oxaliplatin in the poor performance status elderly, and that the well elderly should still get oxaliplatin. Of course, this position does not make sense because the elderly that entered the trials from which we obtained the results were the well elderly, and not the poor performance status patients. So, as the data continue to mature, our enthusiasm falls further.
Analysis of Outcomes Is Practice-changing
This new report from Tournigand and colleagues1 is incredibly important and, in my opinion, it is immediately practice-changing. We give too much oxaliplatin relative to its benefit. I interpret these data such that we should no longer give oxaliplatin in patients with stage II disease or the elderly. And, I am hopeful that the current trial comparing 3 months to 6 months of treatment will accrue quickly and give us further support to reduce our treatment duration, further reducing the risk of neuropathy.
Oncologists are incredibly enthusiastic about adjuvant therapy. We love to give it, we love to push doses, thinking this will increase cure rates. But, frankly, we must first remember that 5-FU remains the most important drug, that oxaliplatin adds little even in the middle-aged stage III patients, and that we need to look to new strategies to improve outcomes. ■
Disclosure: Dr. Marshall has served as a consultant for and has received honoraria from Genentech and Amgen.
Reference
1. Tournigand C, André T, Bonnetain F, et al: Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: Subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer Trial. J Clin Oncol 30:3353-3360, 2012.
John L. Marshall, MD, is Professor of Oncology and Medicine, Associate Director of Clinical Research, and Director, Experimental Therapetucis and GI
