Breast Cancer Update .com - Web Guide 2

Tracks 1-6

Track 1	Introduction
Track 2	Rationale for incorporating nab paclitaxel into the adjuvant setting
Track 3	Pilot study of dose-dense AC followed by nab paclitaxel in the adjuvant setting

Track 4	Utilization of growth factor support with dose-dense chemotherapy regimens
Track 5	Substituting epirubicin for doxorubicin in the adjuvant setting
Track 6	Schedule of nab paclitaxel

Select Excerpts from the Breast Cancer Update Meet The Professors Session, held at the 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005

Track 2-3

DR LOVE: Would you comment on your paper evaluating dose-dense AC

nab paclitaxel and the rationale for the study?

DR ROBERT: Right now, where I practice — and I believe throughout the United States — when we utilize adjuvant chemotherapy, we either use dose-dense chemotherapy or TAC. Paclitaxel with Cremophor^® is a good drug but it requires steroid premedication, as patients can experience severe allergic reactions. The question is whether there is a better way to deliver it.

Nab paclitaxel is well tolerated — you don’t have to worry about hypersensitivity or premedication with steroids. I think it was really novel to use albumin rather than Cremophor as the solvent. The interesting part of that story was the idea that albumin as a solvent might bring drugs closer to the tumor and be more effective in addition to being easier to administer.

We had a discussion about the standard in adjuvant chemotherapy and decided that the dose-dense ACT regimen was here to stay — certainly the disease-free survival data are holding — and since nab paclitaxel looked better than paclitaxel in the Phase III trial (Gradishar 2005), we wanted to evaluate it in the dose-dense setting.

We started with a simple study of 30 patients and administered AC with growth factor support every two weeks and then nab paclitaxel, 260 mg/m², without growth factor support (Robert 2005) every two weeks.

All 30 patients got through the AC portion, with three requiring dose delays and two requiring dose reductions.

In the nab paclitaxel portion, 33 percent of the patients received growth factor support due to lack of recovery of ANC to at least 1,000 cells/mm3 by the first day of the following cycle.

Also, of the patients who received nab paclitaxel, one patient went off study because the HER2 data were released and she wanted to receive trastuzumab, and two other patients were unable to complete the study. During nab paclitaxel treatment, approximately a third of the patients had a dose delay, and about a third experienced neurotoxicity.

However, as in the Phase III study (Gradishar 2005), in our trial, we found that once the patient develops neurotoxicity, if we reduce the dose, the neurotoxicity decreases.

We’re still examining those data, but the majority of our patients improved their grade in terms of neurotoxicity within a month. So, by the time we finished administering all four cycles, the neurotoxicity was diminished.

In addition, the majority of patients were experiencing Grade II symptoms — which are livable — versus Grade III, which is when the patient is having problems with daily functioning. So it doesn’t appear that neurotoxicity is a problem; the issue is whether we need to be concerned about dose delay with nab paclitaxel.

Preliminary results indicate that dose-dense AC for four cycles followed by nab paclitaxel, 260 mg/m², every two weeks was well tolerated in patients with early-stage breast cancer. However, further studies of that regimen in this population are indicated.

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