Source: J Clin Otorhinolaryngol  |  Posted 7 years ago

W. A. Thomasson, PhD

CHICAGO, IL -- November 4, 2004 -- Results of phase 3 clinical trials indicate that an albumin-bound paclitaxel formulation (Abraxane) is more effective than unbound paclitaxel in taxane-naive patients with metastatic breast cancer and have some activity in patients with taxane-resistant tumors.

William Gradishar, MD, of Northwestern University in Chicago, Illinois, presented data from these trials here on November 1[^]st[] at the Lynn Sage Breast Cancer Symposium.

With colleagues from American Bioscience, Inc, Santa Monica, California, and Baylor-Charles A. Sammons Cancer Center, Dallas, Texas, Dr. Gradishar compared a regimen for taxane-naive patients including 175 mg/m[^]2[] unbound paclitaxel or an ABX dose of 260 mg/m[^]2[] paclitaxel. Both drugs were delivered every 3 weeks as intravenous infusions, the unbound paclitaxel over 3 hours with standard dexamethasone and antihistamine premedication, the ABX over 30 minutes with no premedication.

Two hundred twenty-nine patients received ABX and 225 the unbound paclitaxel. In the overall group, 179 patients were receiving the trial medication as first-line therapy while 275 had previously received non-taxane chemotherapy.

Albumin-bound paclitaxel produced a higher total (complete plus partial) response rate both in the overall group (33.2% versus 18.7%, p = 0.001) and in patients receiving first-line therapy (42.3% versus 27.0%, p = 0.029). Time to tumor progression was also longer in the albumin-bound paclitaxel group, again both for the entire patient group (21.9 versus 16.1 weeks, P =.03) and for those receiving first-line therapy (28.4 versus 21.2 weeks, P =.056).

Toxicity was generally similar between the two regimens, although the ABX group had significantly less grade 4 neutropenia (9% versus 22%, p < 0.001). On the other hand, this group had significantly more grade 3 sensory neuropathy (10% versus 2%, p < 0.001).

Following discontinuation of the albumin bound paclitaxel formulation, however, grade 3 neuropathy improved to grade 1 or 2 in a median of 22 days.

In a second study, 105 patients who either had experienced tumor progression while on a taxane (88%) or who had experienced relapse within 12 months of taxane therapy (12%) were treated with albumin-bound paclitaxel at a weekly dose equivalent to 100 mg/m[^]2[] paclitaxel for 3 out of 4 weeks.

Ninety-one percent of these patients had visceral disease and 65% had more than three metastatic sites.

Of the treated patients, 15% experienced a partial response and another 15% had stable disease for at least 16 weeks. Thirteen percent of patients remained progression-free at 12 months and 38% were alive at that time.

Toxicity was moderate, with two patients who experienced grade 4 toxicities (leukopenia and febrile neutropenia). Grade 3 toxicities other than leukopenia and neutropenia were likewise uncommon.

Albumin-bound paclitaxel appears to be a promising new agent for treatment of metastatic breast cancer. A New Drug Application for the agent was filed in March 2004.

[Presentation title: "Enhanced Activity of Abraxane[^]TM[] in Metastatic Breast Cancer."