You are here: Home: CCU 3 | 2006: Edward Chu, MD

Tracks 1-15

Track 1 Introduction Track 2 Selection of adjuvant chemotherapy for colorectal cancer Track 3 Use of capecitabine in the adjuvant and metastatic settings Track 4 Dose and schedule of capecitabine Track 5 Clinical use of capecitabine in the adjuvant setting Track 6 Management of oxaliplatin-associated neurotoxicity Track 7 Similarities and differences between panitumumab and cetuximab Track 8 Potential advantages of adjuvant CAPOX compared to FOLFOX Track 9 Staging and treatment of patients with rectal cancer Track 10 Selection of chemotherapy to combine with radiation therapy in the treatment of rectal cancer Track 11 Clinical algorithm for first-line therapy in patients without prior systemic therapy Track 12 Clinical implications of TREE-1 and TREE-2 trial results Track 13 Continuation of bevacizumab after disease progression Track 14 Therapeutic approach to patients with isolated hepatic metastasis Track 15 Future directions in the development of biologic agents in colorectal cancer

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Track 2

DR CHU: It’s clear that FOLFOX certainly provides significant clinical benefit to patients with Stage III disease, for whom oxaliplatin-based chemotherapy is FDA approved, but I also believe, based on the MOSAIC trial data, that patients with Stage II disease benefit significantly from FOLFOX (André 2004; de Gramont 2005; [2.1]).

At last year’s ASCO meeting, Norm Wolmark presented the results from the NSABP adjuvant C-07 study, which demonstrated that a bolus 5-FU/ leucovorin/oxaliplatin regimen — FLOX — also seemed to confer significant clinical benefit (Wolmark 2005). We only have three-year disease-free survival data, but if one looks at the improvement with the bolus regimen of FLOX versus the infusional regimen of FOLFOX, they are virtually identical (2.2).

So for patients with a good performance status and very few comorbid illnesses, an oxaliplatin-based regimen is my first choice for adjuvant therapy.

For patients who are older and may have comorbid illnesses, the feeling is they might experience increased toxicity from oxaliplatin-based chemotherapy. In that setting fluoropyrimidine monotherapy is reasonable. Based on the results from the X-ACT trial (Twelves 2005), an oral fluoropyrimidine in the form of capecitabine is effective. If anything, based on the X-ACT trial, it appears to be more active and provide more clinical benefit than 5-FU/leucovorin, with a significantly improved safety profile.

Tracks 3-4

DR CHU: In the adjuvant setting, as per the X-ACT trial (Twelves 2005), the dose of capecitabine initially was 1,250 mg/m² twice a day on days one through 14 every 21 days. As it turned out, up to 42 percent of the patients required a dose reduction during the course of the trial. It’s important to emphasize that approximately the same number of patients who were on 5-FU/leucovorin also required a dose reduction.

In the metastatic setting, where we’re not attempting cure but rather palliation, the general experience has been to start patients at a lower dose — 900 to 1,000 mg/m² twice a day (for 14 of 21 days). In combination with either irinotecan or oxaliplatin, at least in the United States, the standard dose we’re now thinking about is 800 to 850 mg/m2 twice a day on days one through 14 every 21 days.

Track 5

DR CHU: It is not too different from my approach to patients with Stage III disease. If you look at the clinical studies and the analyses conducted thus far, there is growing evidence that adjuvant therapy for patients with Stage II colon cancer confers benefit, although the benefit is less than that seen in Stage III disease.

Out of every 100 patients with Stage II disease whom we treat, probably at most two to four patients may benefit, and among patients with Stage III disease, probably six to eight would benefit. In my practice, I tend to be fairly aggressive and have, in fact, offered FOLFOX to patients with Stage II disease. Recently, I was referred a patient who was a music professor at our university. They were concerned about the possibility of oxaliplatin-associated neuropathy as this individual was a pianist, so we used capecitabine.

Track 12

DR CHU: The TREE-1 study was initially developed by Howard Hochster at NYU to evaluate the toxicity, safety profile and clinical activity of three different oxaliplatin-based regimens (Hochster 2005). One regimen was a modified FOLFOX-6. Another regimen was bolus 5-FU/leucovorin in combination with oxaliplatin that Howard developed, which had shown very promising results in the Phase II setting (Hochster 2003). The third regimen in TREE-1 was capecitabine with oxaliplatin.

When it became evident that bevacizumab was going to be approved by the FDA, the trial was then modified to the TREE-2 study. It involved the same three arms of oxaliplatin-based chemotherapy with the addition of bevacizumab.

At the 2005 ASCO meeting, Howard reported that the bolus schedule was inferior in clinical activity and was associated with increased toxicity. The modified FOLFOX-6 and the CAPOX regimens were nearly identical, at least in terms of response rate, although it did seem that the modified FOLFOX-6 was slightly better (Hochster 2005; [2.3]).

DR LOVE: How are you approaching the selection of capecitabine versus 5-FU in combination with bevacizumab and oxaliplatin?

DR CHU: The TREE-2 study provides the rationale for substituting capecitabine for infusional 5-FU, and we’re generally using CAPOX and bevacizumab.

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Editor's Note:
Son of FOLFOX
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Edward Chu, MD
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Robert A Wolff, MD
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Howard A Burris III, MD
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