You are here: Home: CCU 5 | 2007: Herbert I Hurwitz, MD

Tracks 1-19

Track 1 Clinical decision-making in the use of adjuvant therapy for patients with Stage II CRC Track 2 Counseling patients about the risks and benefits of adjuvant therapy Track 3 Use of adjuvant capecitabine monotherapy for patients with lower-risk disease Track 4 Monitoring patients for oxaliplatin- associated neuropathy Track 5 Dosing capecitabine monotherapy in the adjuvant setting Track 6 Patient follow-up after adjuvant therapy Track 7 Management of potentially curable mCRC Track 8 Treatment algorithm for resectable versus unresectable mCRC Track 9 Utilization of response to preoperative therapy as an in vivo test of chemosensitivity Track 10 Therapeutic approach to unresectable mCRC and an asymptomatic, synchronous primary tumor Track 11 Avoidance of surgical intervention for patients with intact, asymptomatic primary tumors Track 12 Selection of appropriate patients for first-line therapy with a fluoropyrimidine bevacizumab treatment platform Track 13 Addition of bevacizumab to FOLFOX versus FOLFIRI for the treatment of mCRC Track 14 Use of treatment holidays in the management of mCRC Track 15 Dosing of bevacizumab Track 16 Continuation of bevacizumab after disease progression: The iBET trial Track 17 Treatment after progression on first-line FOLFOX/bevacizumab Track 18 Reintroduction of oxaliplatin after discontinuation due to drug-related toxicity Track 19 Clinical trial endpoints in the evaluation of biologic and targeted agents

Select Excerpts from the Interview

Tracks 1, 3

DR HURWITZ: The biggest questions regarding chemotherapy in the adjuvant setting have to do with stage, namely lymph node-positive versus node-negative disease, and to some degree, the existence of any additional risk factors (eg, an inadequate number of lymph nodes). The debate surrounds whether patients with lymph node-negative disease or those with Dukes B₂ — or Stage II — cancer benefit from therapy. I usually address that issue by having a long discussion with the patient. I explain that the relative benefit for these patients is probably similar, but because the absolute risk is less, the absolute benefit is also smaller, but it still may exist.

DR LOVE: How do you approach the treatment of patients with lower-risk disease, and where does capecitabine fit in?

DR HURWITZ: Settings arise in which patients have preexisting neuropathy or have careers or lifestyles for which neuropathy would be a major quality-of-life adjustment. I’ll let them know that they have two options: FOLFOX, which probably has a slightly superior outcome, or capecitabine as monotherapy — or if for some reason that would not be available, 5-FU is probably better than nothing from the point of view of disease control and survival.

DR LOVE: You mentioned the option of capecitabine monotherapy. How do you dose in that setting?

DR HURWITZ: For monotherapy, most patients in the US will begin with 1,000 mg/m² twice daily for two out of three weeks (1.1). The dose will be increased if they don’t have problems in the first cycle. For patients with an excellent performance status, it is reasonable to start at the full 1,250 mg/m² twice daily.

Tracks 12-13

DR HURWITZ: The main issue in the metastatic setting is whether the patient is a candidate for systemic therapy. The second issue is the presence of any major contraindications to the backbones of therapy, which would be either a fluoropyrimidine or bevacizumab. A quick family history will tell you if any family member has had problems receiving chemotherapy. If a family member has a dihydropyrimidine dehydrogenase (DPD) deficiency and could not metabolize pyrimidines, usually everybody in the family has been alerted.

Another issue would be bevacizumab-specific contraindications. Recent (six months to one year) arteriovascular complications — myocardial infarction, stroke or active disease — are fairly significant contraindications to bevacizumab.

DR LOVE: Is the use of bevacizumab as beneficial with an oxaliplatin-containing regimen as it is with an irinotecan-based regimen?

DR HURWITZ: I don’t believe it’s an issue of oxaliplatin versus irinotecan. In the second-line FOLFOX study from Dr Giantonio (ECOG-E3200; [Giantonio 2007]) — FOLFOX/bevacizumab versus FOLFOX alone versus bevacizumab monotherapy — the benefits in terms of response rates and survival with the addition of bevacizumab to second-line FOLFOX were significant. The improvements using bevacizumab were as large as those in any other study, and the second-line setting probably includes a harder-to-treat population.

A comparison of other data to those of the first-line NO16966 study of bevacizumab with oxaliplatin (Saltz 2007) is confounded by several clinical study variables. The FOLFOX/CAPOX/bevacizumab data (1.2) do not appear as positive as those using the bolus IFL regimen. However, bolus IFL is not the best platform to use in the first-line treatment of colorectal cancer.

Track 14

DR HURWITZ: One approach is to be preemptive through the use of a calendar schedule. This is the OPTIMOX (Tournigand 2006) approach, by which stopping and starting treatment are based as much on the calendar as they are on the patient’s symptoms or disease control.

I find that adjustment based on the patient’s symptoms — as long as the threshold of symptoms is lowered — ends up being a nearly identical approach. I have a bias to try to adjust based on how the patient is faring rather than the calendar, but in practice, the two approaches are most likely similar.

DR LOVE: When you stop oxaliplatin, do you continue the 5-FU or capecitabine and the bevacizumab?

DR HURWITZ: Yes, currently my algorithm is to reduce or stop only the problem agent and to continue the portions of therapy that seem to help, as long as they’re well tolerated.

For patients who need a break for personal reasons, or for asthenia, I believe stopping even the fluoropyrimidine and bevacizumab for a period of several weeks to two months is a reasonable approach, as long as the disease burden and patient symptoms allow for the holiday.

Track 16

DR HURWITZ: If the disease clearly progresses on therapy, that therapy, whatever it is, should be stopped and patients should receive whatever other options seem reasonable. The difficulty — particularly if progression is slow — is knowing whether the slow progression is attributable to bevacizumab or to indolent disease. That’s why we have to use our best judgment until we see better data.

The cooperative groups are running a study known as iBET (1.3). This will address the question of whether patients fare better with bevacizumab continued into that “second-line” setting and whether they respond better to the 5-mg versus the 10-mg dose.

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