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New data from an innovative head-to-head phase II study of Abraxane (paclitaxel protein-bound particles for injectable suspension [albumin bound], Abraxis BioScience) versus standard Taxotere (docetaxel, Sanofi-Aventis) showed that weekly Abraxane boosted the tumor response rate by more than 60% over Taxotere given every three weeks in first-line treatment of metastatic breast cancer.
"Additionally, there was significantly less toxicity with weekly Abraxane (also called ABI-007) than with the standard FDA-approved dose of Taxotere given every three weeks," said lead investigator William Gradishar, M.D., FACP, director, Breast Medical Oncology, Northwestern University, Chicago. "The novel agent was well tolerated." Of importance is that when the Food & Drug Administration approved Abraxane in 2005, it classified [the new agent] as a "protein-bound taxane particle," he pointed out. "It was the first compound in this new class of drugs and represents the next-generation taxane."
The current phase II study results, "which were consistent with those from previous studies of these agents," support the increasingly popular 'dose-density hypothesis' that claims certain chemotherapy agents are more effective when administered at the highest dose possible as frequently as possible, Gradishar noted in his presentation at the recently held 29th Annual San Antonio Breast Cancer Symposium. As a result of the promising findings, he said, Abraxis is launching a large worldwide phase III trial comparing weekly Abraxane to every-three-week Taxotere to treat first-line metastatic breast cancer. In the phase II study, some 300 chemotherapy-naïve patients with stage IV metastatic breast cancer received one of four regimens: ABI-007 300 mg/m2 dosed every three weeks; ABI-007 100 or 150 mg/m2 dosed weekly for three weeks out of four ("week 4 was a break"); or Taxotere 100 mg/m2 dosed every three weeks. "We evaluated each drug's toxicity and tumor response data; studied the results of weekly versus every-three-week dosing of Abraxane; then compared a high and a low dose of Abraxane."
As for survival issues, "we found that all three ABI-007 regimens had longer progression-free survivals than docetaxel dosed every three weeks," Gradishar added. In fact, to date, twice as many patients on Taxotere have progressed and/or died compared with those on each ABI-007 arm, according to his report. Similarly, when it came to tolerability, all three ABI-007 treatment arms boasted far fewer side effects particularly when neutropenia, febrile neutropenia, or mucositis were involved.
"The new drug is significantly superior to the standard treatment, in that using it weekly showed reduced white blood cell counts, fewer patients in the hospital with infections, and fewer painful mouth sores," Gradishar said. "We did find fewer arthralgias and myalgias in the Taxotere group." These annoying muscular aches and pains often accompany high-dose taxane treatment, he added; they typically are self-limiting, treated with acetaminophen, and resolved without dose modification or interruption.
"A major problem with taxanes," Gradishar emphasized in the Drug Topics interview, "is that they cannot be dissolved in water. This meant, until now, that the only way to dissolve and deliver taxanes was to combine them with highly toxic solvents such as polyethylated castor oil."
Abraxis scientists got around this problem "with an innovative approach that 'deceives' the natural biologic pathways of tumors with a proprietary drug delivery system-a nanoparticle albumin-bound, tumor-targeting technology," Gradishar explained.