You are here: Home: CCU 2 | 2007: John L Marshall, MD

Tracks 1-17

Track 1 Introduction Track 2 Use of bevacizumab after discontinuation of chemotherapy or beyond disease progression Track 3 Incorporation of panitumumab into clinical practice Track 4 Infusion reactions with cetuximab versus panitumumab Track 5 Treatment of potentially curable metastatic disease Track 6 Management of synchronous primary and metastatic disease Track 7 Patient acceptance of cetuximab-associated rash in trials of adjuvant therapy Track 8 Capecitabine alone or with oxaliplatin for the treatment of Stage II disease Track 9 Treatment of lower-risk breast and colon cancer Track 10 Patient acceptance of adjuvant therapy for modest benefits Track 11 Patient expectations about chemotherapy side effects Track 12 A physician’s experience with a spouse being treated for breast cancer Track 13 Impact of a personal experience with cancer on the practice of oncology Track 14 Communication and children’s coping with a parent’s cancer Track 15 The personal decision to participate in a clinical trial Track 16 Impact of cancer diagnosis and treatment on lifestyle and relationships Track 17 A personal perspective on the pace of progress in cancer research

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Track 2

DR MARSHALL: I tend to follow an OPTIMOX-type strategy. Whether I’m administering OPTIMIRI or OPTIMOX, I back off from irinotecan or oxaliplatin after I see the optimum response, which is usually around four months of therapy. Generally, I continue with 5-FU and bevacizumab.

The recent OPTIMOX-2 data have given us permission to not administer any agent during the chemotherapy-free window, so you could stop treatment altogether (Maindrault-Goebel 2006; [1.1]). However, as a clinical trialist, I believe that may be the ideal opportunity to bring in new medicines.

We are beginning to design more trials to test new agents in the chemotherapy-free window to see if they are able to stabilize or prolong progression.

When patients reprogress on one regimen, I change to the other base chemotherapy. However, many physicians like to resume the old chemotherapy: If the patient was on oxaliplatin, they bring back the oxaliplatin, and if the patient was on irinotecan, they bring back the irinotecan.

DR LOVE: When you switch regimens, do you continue the bevacizumab?

DR MARSHALL: At that point, I frequently bring in an EGFR blocker, even though that has not yet been established by the data. More recent trials support the practice of not waiting until the disease becomes irinotecan refractory before bringing in an EGFR inhibitor. In fact, data for the EGFR inhibitors now indicate that in almost every setting they’ve been tested in — last line, second line, and now we have some first-line data — they’ve shown a positive impact (Tabernero 2004).

DR LOVE: When you make this decision with the patient whose disease is progressing, do you factor in how they responded to the treatments?

DR MARSHALL: Yes. If they progressed rapidly or didn’t respond well, I’m less enthusiastic about keeping a drug on board, so I’ll switch it. But if they’ve received a nice benefit from a drug, I don’t usually give that up.

With bevacizumab, you can recognize a change in the biology of these tumors — they slow down. It’s not necessarily that the tumors respond further, it’s just that you have “turned them off,” so I hesitate to pull patients off of bevacizumab. Clinically, that’s what we’re seeing — this quieting of colon cancer and long-term survivors with metastatic disease.

Track 3

DR MARSHALL: One of the most common questions I’m getting right now is, “I’ve used cetuximab. Should I now administer panitumumab?” My answer has been no.

However, I’m beginning to gain a little more experience with this patient population, and I administer a lot of BOND-2, last-line regimens (Saltz 2005). Recognizing that BOND-2 is with anti-EGFR or anti-VEGF treatment-naïve patients, I will not let patients continue to progress without combining EGF and VEGF inhibitors at some point. Clinically, when you put the two antibodies together, you see fairly consistent activity, even in the nonnaïve and the previously exposed patient.

I have been using cetuximab, and now I have patients who would like to take the week off. They’re coming to me and saying, “Can I switch off and go to panitumumab?” and I say, “Sure.” What’s interesting is that when I do so, I see a little more renewed activity. I’m also seeing a renewed rash. A lot of patients whose cetuximab rash quieted down are now receiving panitumumab.

Track 5

DR MARSHALL: In general, I am increasingly adopting a chemotherapy-first approach. In my opinion, patients who are going to benefit the most from a surgical approach — a resection of the metastatic lesion — are those who respond to chemotherapy (Delaunoit 2005).

The marker, if you will, of a responding metastatic lesion is encouraging and powerful, so more and more patients are being offered surgery for oligo-metastatic disease. We’re now having an opposite problem — a good problem.

I’m taking care of a young man right now who has a rectal tumor with two liver metastases and is on a capecitabine trial.

After two rounds of CAPOX and bevacizumab, he has had such a good response that we can barely see his two liver metastases, and his rectal lesion has shown a nice response.

If I keep going too much more with chemotherapy, we’re not going to be able to find the lesions to resect. Not that I think chemotherapy cured the patient, but the lesions are now not detectable. What a good problem to have. Now we have to dance that dance and make sure we don’t mismanage the rectal area and that he still has a shot at a liver resection.

Our decision is that after four cycles we’re going to restage his cancer, then pause and administer neoadjuvant radiation therapy, maintaining some capecitabine and probably some oxaliplatin during that radiation therapy. We will restage after that, and then most likely perform a rectal resection, and at the same time, instead of a lobectomy, perform radiofrequency ablation on the residual tumors.

DR LOVE: What is seen histologically in people who have clinical complete responses in the liver?

DR MARSHALL: A lot of these people still have residual disease, but some don’t.

DR LOVE: How do you decide whether or not to resect the area?

DR MARSHALL: It’s a good question. For this particular patient, I called the surgeon and asked, “What would you do if you got in there and you couldn’t see it?” He knows anatomically where the lesions were, so he can resect the region that they were in. It’s also important to note that even when traditional imaging shows nothing, an ultrasound can find areas of disease. I was a little nervous when this patient’s response was so good, thinking that we then wouldn’t be able to perform what we hoped would be a curative resection on his liver.

Track 8

DR MARSHALL: On one side, it’s clear that we’re dramatically overtreating patients. We’re administering chemotherapy to 100 patients to help what may be three to six people in the long run. I’m not fundamentally against that, but I would like to figure out who may benefit and administer chemotherapy to them. We are trying to recruit to a clinical trial (ECOG-E5202) that groups patients according to the tumor’s genetic markers, and we’ve had some luck.

For the most part, patients are interested in pursuing chemotherapy. Patients with education — whether it’s fair education or not — will opt to receive chemotherapy. My feeling is that community physicians are treating more of these people than they were before. They’re also using a lot more capecitabine in this patient population.

DR LOVE: So for the patient at lower risk, some physicians are opting for capecitabine alone because they “want to do something.”

DR MARSHALL: Yes, which doesn’t make sense to me. If you’re going to do it, do it. The data say that FOLFOX would pick up a couple more people than capecitabine by itself. I’ve heard Aimery de Gramont say this, and I agree with him. If I were a Stage II patient, I’d rather receive three months of FOLFOX than six months of capecitabine alone.

DR LOVE: What about using capecitabine with oxaliplatin (CAPOX) in the adjuvant setting?

DR MARSHALL: The metastatic data with capecitabine and oxaliplatin, whether it’s infusion or bolus, are positive. So it is probably fine, and then I put in my little asterisk and say, “But I’ve been wrong before.”

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Editor:
Neil Love, MD

Interviews:

John L Marshall, MD
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Leonard B Saltz, MD
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James Cassidy, MD
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