You are here: Home: CCU 4 | 2006: Mace Rothenberg, MD

Tracks 1-15

Track 1 Introduction Track 2 Recent trends in colorectal cancer clinical research Track 3 Combining bevacizumab/ cetuximab plus chemotherapy Track 4 Multimodality therapeutic approach to patients with hepatic-only disease Track 5 Role of aggressive surveillance in earlier detection of recurrent disease Track 6 Adjuvant therapy for patients with Stage II/III colon cancer Track 7 Clinical implications of the X-ACT adjuvant trial comparing capecitabine to 5-FU/LV Track 8 Dosing capecitabine in the adjuvant setting Track 9 Substitution of capecitabine for 5-FU in combination with oxaliplatin Track 10 Current generation of adjuvant trials in colon cancer Track 11 Potential side effects of biologic agents in the adjuvant setting Track 12 Oxaliplatin-associated neurotoxicity Track 13 Advances in the treatment of rectal cancer Track 14 Incorporation of capecitabine and oxaliplatin into neoadjuvant trials in rectal cancer Track 15 Clinical and research developments in colorectal cancer presented at ASCO 2006

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Track 6

DR ROTHENBERG: The MOSAIC trial from Europe (André 2004) and the C-07 trial from the NSABP (Wolmark 2005) both demonstrated that the addition of oxaliplatin to 5-FU/leucovorin improved three-year progression-free survival by approximately four to five percentage points, which was significant in both trials (1.1).

We have to be concerned about long-term toxicity with these kinds of regimens. If we counsel patients about potential permanent but mild neuropathy and they’re accepting of this, then we have no reason not to administer oxaliplatin/5-FU/leucovorin — whether we use the schedule that the NSABP used, on which a lower total dose of oxaliplatin was administered, or the every two-week infusional 5-FU regimen from the MOSAIC trial.

An important clinical trial is being performed in ECOG and through the cooperative groups that’s evaluating risk assessment of Stage II patients based on 18q deletion and microsatellite instability (MSI; [1.2]).

If patients have favorable characteristics for microsatellite instability — basically, MSI high and no 18q deletion — they are assigned to observation only.

If patients have one or two bad characteristics from this molecular analysis, they will be randomly assigned to either six months of FOLFOX or six months of FOLFOX and bevacizumab.

DR LOVE: How do you approach the treatment of Stage II disease off protocol?

DR ROTHENBERG: I would probably look at these characteristics, although I have been in situations in which test results have come back conflicting — one criterion suggesting a good-prognosis tumor and another suggesting a poor-prognosis tumor. So it has ended up being rather puzzling and confusing to me.

I hope the results of the clinical trial that I just described will help. Often, the situation is resolved by talking to the patients and finding out whether they are most concerned about side effects from treatment and inconvenience, whether they feel comfortable in a watch-and-wait mode or whether they want to go to great lengths to try and eradicate every last cancer cell that might be lying dormant and are willing to withstand four to six months of adjuvant treatment along with the potential risks and side effects.

I try to use what patients tell me to determine the recommendation for whether they receive treatment or not. I can’t say that I follow a “one-size-fits-all” approach when it comes to Stage II colon cancer.

Track 7

DR ROTHENBERG: This study compared single-agent capecitabine to the Mayo Clinic regimen of 5-FU/leucovorin for patients with locally advanced colon cancer. It was conducted as a noninferiority trial to find out whether 5-FU and leucovorin could be replaced by an oral agent. The bottom line was that it could.

In some measures of activity, capecitabine was trending toward being a little bit better than 5-FU/leucovorin (1.3).

I believe this is a very important trial — it’s been published in The New England Journal of Medicine (Twelves 2005) — and it showed that we have an option for individuals who may not want to come into a clinic on a weekly basis because of their work or travel schedules and are willing and able to comply with an oral dosing regimen of capecitabine.

The side effects associated with capecitabine are different from those of the bolus 5-FU. You have a little bit less mucositis and myelosuppression, but you have a little bit more in the way of hand-foot syndrome.

It is important to note that both regimens can result in diarrhea. So patients must understand which side effects they’re most likely to encounter, whom to contact and what to do about those side effects.

Track 8

DR ROTHENBERG: That’s a tough question because I’m always concerned about citing statistics from a trial and then not giving the same doses that were given in the trial. I would probably not start at 2,500 mg/m^2* but at 2,000 mg/m² and then monitor the patient very closely. If the patient tolerated the drug well, I would escalate the dose to 2,500 mg/m² by the second cycle. If he or she were having some side effects of concern but they were manageable, I’d stay at 2,000 mg/m².

The key is to dose at the optimum or maximum-tolerated dose for each patient. If the patient is experiencing tolerable Grade II toxicities, he or she is receiving enough of the drug.

* Two divided doses for 14 of 21 days

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