You are here: Home: CCU 3 | 2007: Alan P Venook, MD

Tracks 1-12

Track 1 Incorporating drug “holidays” in the paradigm of treating metastatic colorectal cancer Track 2 Case discussion: A patient with a good response to FOLFOX/ bevacizumab with multiple treatment holidays Track 3 Chemotherapy before surgery in potentially curative settings Track 4 Current research and treatment issues in rectal cancer Track 5 Clinical approach to adjuvant therapy for patients with rectal cancer Track 6 Clinical trials incorporating EGFR inhibitors as first-line therapy Track 7 Continuation of bevacizumab after disease progression Track 8 Use of panitumumab for patients with advanced colorectal cancer Track 9 Major ongoing adjuvant clinical trials in colon cancer Track 10 Patient acceptance of rash as a side effect of adjuvant therapy Track 11 EVEREST: Cetuximab dose escalation study for patients with metastatic colorectal cancer and no or slight skin reactions to cetuximab standard dose treatment Track 12 Evolving data on capecitabine with oxaliplatin in the adjuvant and metastatic settings

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Track 2

DR VENOOK: I’ve always been a proponent of drug holidays without any basis for it — I just rely on common sense and try to do the best thing possible for my patients.

One of my patients is approximately four years into his metastatic disease. He initially responded to front-line FOLFOX/bevacizumab therapy and then developed neuropathy. We gave him six months off the treatment. During that time, his disease progressed a bit and the neuropathy was persistent. We switched to FOLFIRI and bevacizumab at the time of progression.

DR LOVE: So you stopped everything — is that what you normally do?

DR VENOOK: This was some years ago, and we stopped everything for that patient. Now my instinct is to continue the components of therapy without the oxaliplatin.

This patient was switched to FOLFIRI/bevacizumab and had another response, which then peaked. His neuropathy resolved, and his disease progressed.

We went back to FOLFOX and bevacizumab, and he responded again. He’s four years out now on cetuximab and responding.

Track 6

DR VENOOK: A study that has not yet opened but will be important to clinical practice patterns is the iBET trial (SWOG/NCCTG/NCIC iBET S0600). It will evaluate whether to continue bevacizumab for patients experiencing progression on first-line chemotherapy and bevacizumab.

Patients experiencing progression on FOLFOX/bevacizumab will be randomly assigned to either irinotecan/cetuximab or irinotecan/cetuximab and bevacizumab.

This trial will approach the biggest question I’m asked regularly: “Do you continue bevacizumab or don’t you continue bevacizumab at the time of progression?”

DR LOVE: How do you approach that sort of situation outside of a protocol?

DR VENOOK: Generally, our instinct is to not continue bevacizumab, although I’ll admit we often reintroduce it later on.

For a 30-year-old whose risk of stroke or myocardial infarction I believe to be sufficiently low, I might keep it going. For a 70-year-old with whom I suspect I’ve already tempted fate, I might stop. I don’t have a one-size-fits-all answer.

DR LOVE: Do you factor in how the patient’s tumor is responding to the therapy?

DR VENOOK: Yes, although it can cut either way. For a patient who shows a dramatic response but whose treatment is only palliative, you could argue to stop the bevacizumab because you’ve already obtained considerable value out of it.

The other way to look at it is, don’t stop the bevacizumab because it may be contributing to the response. So it’s a gray area. There’s very little black and white about the decision.

Track 9

DR VENOOK: We enroll patients on ECOG-E5202, which I believe is an incredibly important study. Patients with Stage II disease are risk stratified based on the molecular features of their cancer (1.1).

Patients at low risk, who are expected to comprise about 60 percent of the patients, are observed. Patients at high risk — deletion on 18q, microsatellite stability — receive FOLFOX or FOLFOX/bevacizumab.

I believe that’s such an absolutely important study to distinguish who doesn’t need chemotherapy and to see whether the data hold up. It would be wonderful to save so many patients from exposure to chemotherapy.

We’re also participating in the Intergroup study (CALGB-80203), evaluating FOLFOX or FOLFIRI with or without cetuximab (Venook 2006).

Track 12

DR VENOOK: In the adjuvant setting, we’re not there yet. We do have data “in the hopper” — the AVANT trial. In the next year we hope to have information that might tell us it’s safe, and at least equivalent, to substitute capecitabine for 5-FU.

Dr Cassidy conducted a study in the metastatic setting (NO16966) that is complex (Cassidy 2006). It was initially a CAPOX versus FOLFOX regimen. Then it was amended to be CAPOX with bevacizumab or placebo versus FOLFOX with bevacizumab or placebo.

The overall take-home message is that CAPOX does not appear to be inferior to FOLFOX in the advanced disease setting. I believe we can take that to the bank, except this was almost entirely a European trial.

The dose of capecitabine in this trial, 1 g/m² BID with oxaliplatin, is a larger dose than we use in the United States. A lot of data suggest, for not entirely certain reasons, that you can’t dose patients in the United States at the same dose of capecitabine that you can use in Europe.

So with the caveat that you have to ensure that the dosing is okay, I believe CAPOX is not inferior to FOLFOX.

With the addition of bevacizumab, overall, patients did better. Progression-free survival was improved. However, it is curious that the incremental benefit of bevacizumab wasn’t nearly as large as it has been with treatments in other colon cancer studies.

DR LOVE: What about the use of capecitabine alone in the adjuvant setting?

DR VENOOK: We use it occasionally. For a patient who isn’t a candidate for FOLFOX — very elderly with comorbidities, neuropathy and the sort of red flags seen with oxaliplatin — we’ll use capecitabine alone.

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