Selection of a Taxane

DR CARLSON: The data suggest that the toxicities associated with nab paclitaxel, compared to paclitaxel in Phase III trials and to docetaxel in Phase II trials, are certainly acceptable and probably less toxic overall. Far fewer allergic infusion reactions but probably more neuropathy occurs with nab paclitaxel.

The toxicity we don’t talk about is time in the infusion center. Nab paclitaxel can be much more rapidly infused, and it is not associated with the toxicities from the premedications that must be used with docetaxel and paclitaxel. So I believe the overall toxicity experience with nab paclitaxel is probably a little more favorable.

I have seen, anecdotally, allergic reactions with nab paclitaxel. They tend not to be infusion reactions but delayed hypersensitivity reactions. At least one was severe enough that the patient required hospitalization. So nab paclitaxel is not a free ride in terms of hypersensitivity, but it does not require premedications because the hypersensitivity reactions are delayed, not immediate.

In approaching the selection of a taxane in my practice, I typically talk with the patient about her goals and her concerns about toxicity. I have used a modest amount of nab paclitaxel as first-line therapy. One factor that sometimes influences my decision is whether I will use bevacizumab in combination with the taxane.

When I use bevacizumab in combination with a taxane, I’m much more likely to use paclitaxel than nab paclitaxel. If I’m planning to use a single-agent taxane in the metastatic setting, I’m currently somewhat more prone to using nab paclitaxel.

I am more likely to use paclitaxel with bevacizumab for several reasons. One reason is that this is where the data came from. When you’re using a clinical trial to justify a treatment, you should try to use the treatment as closely as you can to the way it was used in the clinical trial.

Another reason is that we don’t have a complete understanding of how bevacizumab increases the rates of response. We do know that as a single agent, bevacizumab is associated with low rates of response. When it’s administered in combination with paclitaxel, it seems to produce relatively high rates of response.

One of the theories for that is that bevacizumab increases vascular permeability, which may allow the more efficient diffusion of paclitaxel into the tumor. The mechanism by which the drug gets into the tumor may be positively affected by bevacizumab.

The mechanism for nab paclitaxel getting into the tumor is apparently different. If that difference is real and if the primary effect of bevacizumab is vascular permeability, then using bevacizumab in combination with nab paclitaxel may not be an effective strategy.

Costs of Therapies

DR CARLSON: For many of these newer therapies, cost is a big issue. It’s a big issue for the individual physician, and it’s a big issue for the insurance carriers. I believe it’s an even bigger issue for us nationally in terms of how we as a society will handle the provision of these extraordinarily expensive medications.

The American culture is individualistic — everyone for themselves, a capitalistic view of the world — as opposed to other cultures in which society as a whole is the endpoint. We have to come to grips with this. It’s going to mean, ultimately, that we take a more societal perspective on healthcare costs and healthcare delivery, as opposed to trying to individualize medicine and have unlimited access to therapies and diagnostics.

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