Editor’s Note Is capecitabine the “AC” of adjuvant therapy for colorectal cancer? (And other related analogies to breast cancer as discussed by the faculty for this program)

DR LOVE: Do you think that basic models used in breast cancer — such as relative and absolute risk reduction in adjuvant therapy — also apply to colorectal cancer?

DR SALTZ: I think the comparison of colorectal cancer to breast cancer is correct, and what I anticipated about a decade ago really is happening in our practices. What I said then was that we were GI doctors, but we wanted to be germ cell doctors. We wanted to cure 95 plus percent of our patients, and attempt to decrease the toxicity of curative regimens to figure out how to move the bar up and save those people with rare refractory disease.

We’re not there yet, but along the way, we’ve become like breast cancer doctors. If you think about it, in 1990 it was absurd to talk about second-line chemotherapy for colorectal cancer. Now, with a straight face, we talk about, “What’s your fourth-line treatment? What’s your fifth going to be? You have six drugs. How are you going to use them? How are you going to sequence them?”

We now talk about expecting median survivals of two years for metastatic disease — and that’s median survival, which means a fair number of people being treated with systemic chemotherapy will live three, four or five years with metastatic disease.

This is a huge paradigm shift in colorectal cancer and in GI oncology in general, which has really taken place fairly quickly over the past decade. I said that we were going to become more like breast cancer doctors as an interim step, and I think that’s happened. Breast cancer care has continued to move forward, but we had a lot of ground to make up, and we’ve caught up some of the way.

DR LOVE: In breast cancer, we often use less intense or less toxic chemotherapy for patients with lower risk, node-negative tumors — for example, AC — whereas a patient with a higher-risk, node-positive tumor might receive a more toxic therapy with a greater antitumor effect, which might include a taxane. Do you think that same approach applies in colorectal cancer in terms of using, for example, capecitabine alone in patients with lower-risk, Stage II disease?

DR O’CONNELL: I think so. It’s a matter of looking at the risk-benefit ratio. The risk of treatment is going to be the same regardless of the risk posed by the tumor, but the amount of absolute benefit with chemotherapy is going to be smaller in patients with good prognosis tumors.

So the incremental benefit of adding oxaliplatin along with 5-FU/leucovorin, although real and important, would result in a very small incremental gain for a favorable risk patient with Stage II disease. Therefore, I think it would be reasonable to treat those patients with a less toxic regimen, such as oral capecitabine.

DR HOFF: It’s very interesting how differently people who treat breast cancer and people who treat colon cancer approach the problem. In colorectal cancer, we tend to look at absolute benefit, while in breast cancer, relative risk reduction is taken much more seriously. If you were to look at the relative risk reduction, for example, of FOLFOX over 5-FU/leucovorin for Stage II disease, it’s over 20 percent. Based on that, you might say that FOLFOX should be used for everyone with Stage II disease, which is not the case.

Perhaps because we have not had effective chemotherapy in the past, we have developed a nihilistic approach to colorectal cancer treatment. Although this takes a long time to change, I think it will happen. I think we’ll be using more chemotherapy as our chemotherapy improves.

DR LOVE: If you have a patient who has an 80 percent chance of remaining disease free and that patient turns to you and says, “Could I further improve my odds by taking capecitabine,” what would you say?

DR HOFF: Usually I tell my patients that this is a point of intense controversy, and depending on what study you believe, the absolute benefit in five years will be between two and five percent. I also tell them that there is a cost for that benefit — six months of therapy with some toxicity. Some patients opt to have treatment even for a one percent benefit, and I have had patients who look at me and say, “For five percent? Forget it.” So I let my patients with Stage II disease help with the decision, unless they have strong risk factors. But I discuss it with all of them.

DR LOVE: The approach you just described is exactly what happens in breast cancer, where oncologists are now routinely offering statistics on expected absolute benefits to patients; however, I’m not sure that has occurred in terms of how people generally approach Stage II colorectal cancer.

DR HOFF: I hope we follow that path, because I really think that is the way to go. We should provide information and some direction to patients, but ultimately they have to decide what is acceptable.

— Neil Love, MD
NLove@ResearchToPractice.net