You are here: Home: CCU 3 | 2006: Robert A Wolff, MD

Tracks 1-18

Track 1 Introduction Track 2 Developing long-term strategies for the surgical and systemic treatment of metastatic disease Track 3 Management of patients with synchronous primary and metastatic disease Track 4 Impact of age on management of synchronous primary and metastatic disease Track 5 Time course for surgery after preoperative bevacizumab Track 6 Hepatic resection, ablation or the combination for hepatic metastases Track 7 Applying oncologic “judgment” to management of hepatic metastases Track 8 Clinical use of hepatic arterial infusion Track 9 Necessity of developing criteria and standards for hepatic resection Track 10 CAPOX versus FOLFOX in the adjuvant and metastatic settings Track 11 Comparability of capecitabine and continuous infusion 5-FU in chemoradiation regimens for rectal cancer Track 12 Convenience of neoadjuvant capecitabine versus infusional 5-FU for rectal cancer Track 13 Role of downstaging clinical Stage III disease in selection of adjuvant chemotherapy Track 14 Clinical trial of preoperative capecitabine/bevacizumab with radiation therapy in rectal cancer Track 15 Potential mechanisms of action of bevacizumab Track 16 Incorporation of oxaliplatin into neoadjuvant chemoradiation therapy for rectal cancer Track 17 CONFIRM-1: FOLFOX with or without vatalanib as first-line therapy Track 18 Effects of bevacizumab and chemotherapeutic agents on the liver

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Track 6

DR WOLFF: Steve Curley has published data for patients who have undergone hepatic resection, hepatic resection combined with radiofrequency ablation or ablation only as the means to approach the metastatic component in the liver (Abdalla 2004). The patients who did best had a resection, and the patients who did worse had ablation only. Patients who had a combination of resection and ablation have intermediate results (3.1). So we’re fans of resection whenever possible, if that’s technically doable and we have enough hepatic remnant.

Track 10

DR WOLFF: Enough data are available now that most authorities would say CAPOX and FOLFOX are almost equivalent. If they are not exactly the same in terms of efficacy, they are pretty close.

If we were talking about 5-FU versus capecitabine, a lot of physicians would favor capecitabine over a 5-FU program. This is an individual physician and patient choice, but I personally don’t have any problems using capecitabine with oxaliplatin as part of the standard adjuvant treatment.

The logic would be that capecitabine is equivalent to 5-FU and leucovorin in the adjuvant setting, possibly a little bit better, and certainly less toxic.

FOLFOX is better than 5-FU and leucovorin in the adjuvant setting and, therefore, I believe CAPOX is a reasonable adjuvant substitute.

DR LOVE: What about using CAPOX with bevacizumab?

DR WOLFF: That’s a very attractive program, and this is a question the AVANT trial (3.2) will evaluate in the adjuvant setting: Would CAPOX with bevacizumab be equivalent to FOLFOX with bevacizumab? The most interesting question is whether bevacizumab adds anything in the adjuvant setting. Theoretically, if bevacizumab is an anti-angiogenic therapy, you might question how much benefit that drug could give you in the setting of microscopic metastatic disease.

Lee Ellis has been a strong proponent that bevacizumab is not simply anti-angiogenic therapy; it’s anti-VEGF therapy (Hicklin 2005; Ellis 2005). Data indicate that VEGF receptors are present on the tumor cells (Zhang 2002) and that VEGF may act as an autocrine growth factor for the tumor itself (Masood 2001).

So if you inhibit that pathway, you may obtain a greater benefit in the adjuvant setting. It will be interesting to see the data. Anybody who attempts to predict the result of that trial may be surprised. A difference may exist between bevacizumab and no bevacizumab, but I’ll be surprised if a difference appears between FOLFOX/bevacizumab and CAPOX/bevacizumab.

Track 11

DR WOLFF: That’s a very good question. One of the issues we need to recognize is that we can’t study everything. We have to identify which research questions are the most important to answer.

I personally don’t believe the question of whether capecitabine is superior, inferior or equivalent to infusional 5-FU or bolus 5-FU is so important to answer.

The Memorial group has data from preoperative rectal cancer demonstrating that whether you give patients bolus 5-FU with radiation therapy or infusional 5-FU with radiation therapy, the outcomes are equivalent.

The surprise came with the Intergroup trial, which showed infusional 5-FU as part of adjuvant therapy for rectal cancer was superior to bolus 5-FU (O’Connell 1994). Part of that may have been related to how much of the agent the patients in the bolus 5-FU arm received.

But if we accept the Memorial data — indicating no difference between bolus 5-FU and radiation therapy and infusional 5-FU with radiation therapy as part of a preoperative strategy — it’s very likely that capecitabine will not be inferior to infusional or bolus 5-FU.

Track 14

DR WOLFF: We are studying a combination of capecitabine, administered daily with bevacizumab, which will be administered every two weeks during the course of radiation therapy. Patients receive bevacizumab and capecitabine starting on the first day of the radiation and then receive bevacizumab every two weeks through radiation. After six weeks of rest, they are referred back to the surgeons, at which point the tumor is reevaluated.

This trial opened fairly recently. I’ve just had a patient complete it, and her disease has been downstaged from T3/N1 to T2/N0.

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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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