Lay Summary: Current thinking is that Abraxane can substitute for paclitaxel with less toxicity in combination with Avastin but information is still coming in.
In January 2005, the U.S. Food and Drug Administration (FDA) approved the chemotherapy drug Abraxane, a new formulation of paclitaxel, for treating advanced (metastatic) breast cancer. The approval is for second-line therapy—after another chemotherapy regimen has been used and has stopped working.
Paclitaxel belongs to a class of chemotherapy drugs called taxanes (Taxol (chemical name: paclitaxel) and Taxotere (chemical name: docetaxel) are the most widely known). But taxanes cause serious side effects, including low white blood cell counts (neutropenia), weakness, and infection. Paclitaxel has to dissolve so it can enter the bloodstream. But paclitaxel does not dissolve in water. Up unti now it has been dissolved in Cremophor, a derivative of castor oil. However, Cremophor makes paclitaxel more toxic and more difficult to tolerate. In order to avoid having serious allergic reactions to Cremophor, women must receive steroids before they receive Taxol.
Abraxane provides a new way to make paclitaxel dissolve in water. Instead of Cremophor, Abraxane uses albumin, a natural protein found in the body. A tiny bit of paclitaxel is suspended in each albumin particle. Because albumin is natural to the body, there is no need to take steroids before receiving Abraxane. And since taking Abraxane does not require taking pre-medication to reduce the risk of an allergic reaction, an Abraxane treatment averages 30 minutes compared with three hours for Taxol. In a Phase III research study, Abraxane was compared directly to Taxol in 454 women. The results of a Phase III trial show that cancers responded better to Abraxane than Taxol and stayed under control longer.
Avastin (chemical name: bevacizumab) is an antiangiogenesis medicine that has been approved by the U.S. Food and Drug Administration (FDA) to treat advanced cancer of the colon or rectum when combined with chemotherapy.
Researchers have studied Avastin as a treatment for women with advanced breast cancer. The Eastern Cooperative Oncology Group presented results of that research, called Trial E2100, at both the American Society of Clinical Oncology annual meeting and the San Antonio Breast Cancer Symposium in 2005. They found that women who received Avastin plus the chemotherapy drug Taxol (chemical name: paclitaxel) had a longer time before their cancer worsened than women who got only Taxol. Compared to Taxol alone, Avastin plus Taxol reduced the risk of the cancer progressing by 50%.
It is possible to view Abraxane as a totally new drug or as a different form of palcitaxel. The answer to the above question will depend on which of the two possibilities one affirms. In practice, a study is ongoing:
CA023 A Phase II study of Abraxane with Avastin for Metastatic Breast Cancer. This is a multi-center, open-label, randomized Phase II study in previously untreated patients with metastatic breast cancer to evaluate the antitumor activity and safety of weekly dose-dense ABI-007 (Abraxane) compared to a 2-weekly regimen vs the standard 3-weekly infusion. All patients will also receive concurrent bevacizumab.
The issue is clouded by the recent withdrawal of the FDA indication for Taxol and Avastin.
NCCN 2011 NIV-N,1 lists Abraxane as a recommended first line single drug for metastatic breast cancer.
In as much as NCCN reflects current literature and consensus, Abraxane should be considered medically necessarybased on the current peer-reviewed literature.
However, the combination of Xeloda and Abraxane is not listed by NCCN. A phase II trial(Swartzberg et al) was encouraging in that inerim results of a small study showed:
■Complete responses (complete disappearances of detectable cancer) were achieved in nearly 9% of patients.
■Partial responses (partial regression of cancer) were achieved in 44% of patients.
■Disease stabilization was achieved in 32.4% of patients.
■Overall, this treatment regimen was generally well tolerated.
Unfortunately more study would be required and Abraxane and Xeloda combination should not be routinely used at this time.
Furlanetto J, Jackisch C, Untch M, et al. Efficacy and safety of nab-paclitaxel 125 mg/m(2) and nab-paclitaxel 150 mg/m(2) compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat. 2017 Mar 17
Miller KD et al.Effect of adding bevacizumab to paclitaxel on progression-free survival of patients with previously untreated metastatic breast cancer; results of ECOG 2100 trial. San Antonio Breast Cancer Symposium, 2005. Abstract 3.
M. R. Green et al, Abraxane®, a novel Cremophor®-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer Annals of Oncology 2006 17(8):1263-1268
Link J, Waisman J, Jacobs C. Bevacizumab (Avastin) and albumin bound paclitaxel (Abraxane) treatment in metastatic breast cancer. Proceedings of the 29th Annual San Antonio Breast Cancer Symposium. San Antonio, Texas. 2006; Abstract 1095.
Ran S, Biven C, Trieu V, Desai N. Synergistic effect of albumin-bound paclitaxel (Abraxane) and anti-VEGF-A antibody (avastin) on growth of orthotopic MDA-MB-231 breast tumors as well as lymphatic and pulmonary metastases. Proceedings of the 29th Annual San Antonio Breast Cancer Symposium. San Antonio, Texas. 2006; Abstract 1094
Swartzberg L, et al. Phase II trial of nanoparticle albumin-bound paclitaxel (ABX) + capecitabine (XEL) in first-line treatment of metastatic breast cancer (MBC): interim results. Proceedings from the 2006 Annual San Antonio Breast Cancer Symposium. December 2006. Abstract 1096.