STABLE DISEASE AS CLINICAL BENEFIC

We are entering an era of pure biologic therapy with drugs like trastuzumab. I think many of these new agents are probably more cytostatic than cytocidal — like hormonal therapy. We have to accept that stable disease in a relatively asymptomatic patient is a good thing, particularly if they’re stable for a long period of time. Stable disease for two or three years with a pill or a simple injection without any symptoms is a really worthwhile achievement.

—Stephen Jones, MD

COMBINATION CHEMOTHERAPY IN METASTATIC DISEASE: CAPECITABINE PLUS DOCETAXEL

There is emerging data that combinations like docetaxel/capecitabine might have a survival advantage over docetaxel alone. That’s a big advance. There is an issue about a lack of crossover in the capecitabine/docetaxelstudy, but I updated that at ASCO, and Joyce O’Shaughnessey presented this last year at San Antonio. About 17 percent of the patients on docetaxel did receive capecitabine subsequently. That’s not too different than the frequency of use of capecitabine in this country. Honestly, I was surprised by the results of this trial, but the study has a very convincing and very real survival difference. We haven’t seen that with other combinations of taxanes with doxorubicin. In my practice, I use this combination of capecitabine and docetaxel for some patients — I give them a choice. In a younger patient who wants to be very aggressive, I certainly have to present the combination as an option.

This study points towards the adjuvant situation where we are already using a lot of taxanes. With the right dose, adding capecitabine may not add very much toxicity and may give more of an antitumor effect. The metastatic setting has always been the testing ground for adjuvant regimens. And at least now, we have a solid scientific lead to potentially plug into adjuvant treatment.

When my patients recur after receiving AC in the adjuvant setting I usually use a single-agent taxane, unless they go onto a clinical trial. Then I usually use capecitabine and then vinorelbine. If I’ve used paclitaxel every three or four weeks in the adjuvant setting, I might use weekly paclitaxel as one of the salvage regimens.

I’ve used capecitabine first-line on occasion for a patient who might not want to lose her hair again. That’s one of the big advantages. The study of CMF versus capecitabine as first-line therapy for metastatic breast cancer showed clear equivalence, so I don’t think we lose anything by doing that. Again, it’s matter of patient selection and wishes. I remember a patient with beautiful white hair that regrew after adjuvant chemotherapy. She had been in a clinical trial and had a four-year complete remission with docetaxel. When she recurred, she didn’t want to lose her hair again, and we treated her with capecitabine.

—Stephen Jones, MD

AVOIDING TOXICITY WITH CAPECITABINE

We participated in the initial capecitabine studies, and I think the dose that was approved is a little too high for most patients. Some can tolerate that dose, but you have to be very careful and proactive about hand-foot syndrome. You really have to stop therapy when patients start getting fairly significant symptoms. With patient education, we see much less hand-foot syndrome, and it’s very tolerable. I also don’t keep pushing treatment every three weeks. In some patients, I go to every four weeks. That extra time off really helps. I’ve had patients whom I’ve treated with paclitaxel every four weeks for four years or so, with their cancer in good control. I’ve had patients for two years on capecitabine. It’s a matter of being proactive and spreading the treatments out to try to minimize and prevent the hand-foot syndrome.

—Stephen Jones, MD

PACLITAXEL VERSUS DOCETAXEL IN THE MERASTATIC SETTING

I’m running a trial of first-line docetaxel versus paclitaxel for the U.S. Oncology group. This trial opened in 1995. I personally think there’s a difference between the agents, with docetaxel perhaps being slightly more active but at a higher price with some more toxicity. I think that study will probably close soon, and we will eventually have some data.

Outside the protocol setting, I give patients the choice. It depends on the age of the patient, their general condition and what they want to achieve. I would treat a young patient who wants to be more aggressive with docetaxel-capecitabine. I might use paclitaxel, with a pretty good side-effect profile, every three to four weeks in an older patient.

—Stephen Jones, MD

I tend to use single-agent taxanes. I like to give therapies on a weekly or every-other-weekly basis, because I think aggregate toxicities are more acceptable. Having said that, as far as the unresolvable decision of paclitaxel versus docetaxel, in my own limited experience weekly paclitaxel has proven a little bit more palatable for patients than weekly docetaxel. Weekly docetaxel is a very effective therapy, but has produced some undesirable skin and nail changes, which have made it a little bit more cumbersome for patients with respect to toxicity.

—Kevin Fox, MD

HIGH-DOSE CHEMOTHERAPY WITH STEM CELL TRANSPLANT

We don’t really know what its role is, if any. I don’t think there are a lot of patients right now receiving transplant in community practice off protocol. One of the things that’s happened over the past few years is that rather than every hospital having a stem cell transplant program, it has come back to the big centers with the expertise. This is great, because they are expensive programs that require a lot of infrastructure.

—Linda Vahdat, MD

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