DR SAAB: Ten years ago, at the age of 58, this patient presented with a right breast lump, which was breast cancer. She was found to have diffuse metastatic disease to the bones and was in such pain that she needed radiation therapy to various areas of the skeleton over the subsequent 18 months. The tumor was hormone receptor-positive, and her prior oncologist started her on tamoxifen. Over the ensuing two years, she didn’t respond very well, was found to be resistant to tamoxifen and needed a substantial amount of radiation therapy. She was switched to anastrozole, which again was determined not to be effective.

Eventually, she was offered chemotherapy, which she had declined initially. She was given CMF with filgrastim support over a period of six months. Toward the end of 1999, again because of rising tumor markers, it was determined that the chemotherapy wasn’t working. Her oncologist then tried low-dose paclitaxel every week for three months, and he determined that it didn’t work well.

This lady required morphine all this time, despite radiation therapy. In January 2000, she was started on capecitabine, and she has been on it ever since. For a full five years on capecitabine, she had been morphine-free and pain-free, until three months ago, when her tumor markers started rising again and her pain started to develop in different areas. Obviously, her cancer was coming back. I then started her on docetaxel every three weeks. After the second cycle, her tumor markers went down and she experienced symptom improvement.

DR OSBORNE: When she experienced progression of disease on the hormone therapy, how long had she been on it, and was it more than just markers going up that led to the discontinuation?

DR SAAB: Her symptoms, including pain, persisted, and her markers continued to rise. The CA27.29 and CA15-3 were elevated around 150 to 180 and her CEA was a little higher.

DR GRADISHAR: This patient has had a remarkable course on capecitabine. Capecitabine is one of my favorite chemotherapy drugs. I believe it was probably underrated initially until we learned how to properly dose it and utilize it effectively in both older and younger patients. I think one of the issues is whether combining drugs is better than using single agents in sequence and how you actually define superiority.

One experience, presented by Joanne Blum, evaluated capecitabine plus a weekly schedule of paclitaxel (Blum 2004). When you compare the clinical endpoints in that trial to the every three-week schedule of paclitaxel in both the European and US studies, you see a response rate in the 50 percent range (3.1). In terms of adverse events, they’re modest, with the most prominent one being hand-foot syndrome, and then hematologic toxicities, which were fairly predictable.

DR LOVE: Peter, we have found that clinical research leaders much more commonly use capecitabine than clinicians in practice. What has been your experience with capecitabine?

DR RAVDIN: Capecitabine has some attractive features. I view it, in terms of toxicity and response, as something that bridges the gap between hormonal therapy and intravenous chemotherapy. Particularly when dosed a bit lower than the package insert dose, it’s tolerable for most patients, and they don’t experience nausea, vomiting or hair loss, almost as if they were receiving an endocrine agent. It’s an oral agent, we don’t have to put in a line, so it’s easier for patients to accept. I think all those features make it an attractive agent.

Actually, I’m a little surprised that it isn’t more commonly used in the community, because I think it’s one of those agents that is generally tolerated with repeated use. With a lot of other agents, patients begin to get tired when you get in six cycles.

DR LOVE: Aman, what was your take on the bevacizumab/paclitaxel data initially presented by Kathy Miller at ASCO (Miller 2005a)?

DR BUZDAR: I think if you put it in context, it’s very similar to the data we saw when trastuzumab was combined in the first-line setting: There is a significantly higher response rate, longer control of disease and early evidence that it may have a favorable impact on survival (3.2). Its side-effect profile is unique, but I think most of the side effects are very manageable, and no new side effects were seen in this study.

With regard to this specific patient, would I consider adding a biologic agent to her therapy? The data on capecitabine combined with bevacizumab, unfortunately, did not show a longer time to progression or any favorable impact on survival, although a higher number of patients had an objective response to the therapy (Miller 2005b). So I think these therapies may need to be utilized early on to get the benefit.

DR LOVE: Are you using bevacizumab and paclitaxel in the first-line setting?

DR BUZDAR: I think the data are very compelling, and I feel that it is our responsibility to share that information with every patient who has similar eligibility criteria as those in that ECOG study.

DR LOVE: Kent, what are your thoughts on this?

DR OSBORNE: I certainly wouldn’t use bevacizumab in any situation other than first-line therapy, since that’s where the data came from, so I wouldn’t use it in this patient. But I’m very concerned about the cost of treatment for a few extra months in time to progression. If I had insurance that paid 80 percent, I’m not sure I would elect to receive bevacizumab because 20 percent of a lot of money is a lot of money. I’m very concerned about the cost issue.

DR LOVE: Peter, do you agree with Kent that you would only use it in that specific situation?

Our group has been tracking the bevacizumab story in colorectal cancer. The initial data were presented two years ago with IFL, and yet everybody immediately started using it with FOLFOX, and eventually that combination was shown to be effective. What are your thoughts about using bevacizumab in breast cancer, and what agents would you combine it with?

DR RAVDIN: I largely agree with what Kent has said in that while a lot of expense, and even sometimes a lot of toxicity, is justified in the adjuvant arena, in the metastatic disease arena, enormous expense is sometimes added to the cost of therapy for a relatively small impact. Data from one trial that’s not a crossover trial are not strong enough to make me consider it the standard of care as front-line therapy for everyone with hormone refractory, metastatic breast cancer because I think that would actually break the back of the healthcare system.

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