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Track 4

DR LOVE: Julie, which chemotherapy would you recommend? Would you add bevacizumab in this situation?

DR GRALOW: The key is how much disease she has and how active it is. Did it progress? Was this pericardial tamponade a progression on capecitabine? At some point, I don’t believe it would be unreasonable to go back to tamoxifen. She was off of it for several years before her disease relapsed.

With respect to chemotherapy, she’s never received a taxane. In the metastatic setting, I like weekly nanoparticle albumin-bound (nab) paclitaxel. I would generally try to add bevacizumab early, and I prefer to use it in a first-line setting. I would add it here if I were using chemotherapy as my next step.

DR WOLFF: At Hopkins, we are limited to the FDA-approved label for bevacizumab. I would have used paclitaxel as my first drug of choice for this case. If I were considering bevacizumab at some point, my hand would have been forced to use it in that setting. With her visceral disease, I would definitely have started with paclitaxel and bevacizumab.

PROF CROWN: I believe this woman should receive a taxane. The data, at present, suggest a rough equivalence between weekly paclitaxel and three-weekly docetaxel in the treatment of metastatic disease (Sparano 2008). We don’t have nab paclitaxel in Europe yet. I would probably add bevacizumab once we were certain she wasn’t at risk for postoperative bleeding from her pericardial window.

We now have data with bevacizumab in two randomized trials: the AVADO trial with docetaxel (Miles 2008; [4.1]) and the previous American trial (ECOG-E2100) with paclitaxel (Miller 2007; [4.2]). They both demonstrated an enhanced effect when bevacizumab was added to the taxane.

The magnitude of benefit with bevacizumab in the AVADO trial (Miles 2008; [4.1]) was smaller than the one seen in the trial with paclitaxel (Miller 2007; [4.2]). As a docetaxel fan and aficionado, I would argue that single-agent docetaxel presented a somewhat sterner control group than paclitaxel.

DR LOVE: Kevin, how are you thinking through cases like this?

DR FOX: We’ve tried to not use bevacizumab in any setting other than as first-line therapy. Here we would have been disinclined to try it.

The taxane we are in the habit of using is nab paclitaxel because we have found it to be efficient for patients. The time commitment for the patient is less, which in Philadelphia is a big deal. The toxicity, I believe, is favorable. Conversely, we’re not big fans of docetaxel because the dose often used in clinical trials — 100 mg/m2 every three weeks — is a little harsh.

Generally, we have not added bevacizumab to a chemotherapy regimen when that regimen has failed. I believe that practice may reflect logic, but we have no data to support it.

I wonder if anybody has had any experience with the risk of bleeding associated with bevacizumab in someone whose pericardium had been violated? I certainly would be a little nervous about using bevacizumab with this particular woman for some time.

DR LOVE: What happened with this patient?

DR ASTROW: I used weekly paclitaxel with bevacizumab. I worried about the pericardial window, so I waited two months before starting bevacizumab. She developed no toxicity from that standpoint.

She received paclitaxel and bevacizumab for six months, when she began to develop peripheral neuropathy and headaches. At that point, I stopped all treatment.