In the last 10 years, several new treatments have been approved to treat locally advanced or metastatic breast cancer. Locally advanced breast cancer is breast cancer that has spread beyond the breast to nearby tissues, such as the skin or the chest wall. Metastatic breast cancer is breast cancer that has spread beyond the breast area to other places in the body, such as the bones, lungs, liver, or brain. Both locally advanced breast cancer and metastatic breast cancer are considered advanced-stage disease.
To help doctors know if certain treatments offered more benefits than others for advanced-stage disease, a study compared two newer treatments to an older, standard treatment.
The researchers found that Taxol (chemical name: paclitaxel), a tried-and-true chemotherapy medicine, stops advanced-stage breast cancer from growing longer than two other chemotherapy medicines: Abraxane (chemical name: albumin-bound or nab-paclitaxel) or Ixempra (chemical name: ixabepilone).
The research was published online on June 8, 2015 by the Journal of Clinical Oncology. Read the abstract of “Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab as First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance).”
Abraxane is a different form of paclitaxel than Taxol. Both medicines are taxanes, a powerful type of chemotherapy that can stop cancer cells from repairing themselves and making new cells.
Taxol uses a solvent called Cremophor EL to dissolve its main ingredients so the medicine can enter the bloodstream. Cremophor EL can make Taxol harder to tolerate. So people usually take medicine before receiving Taxol to minimize any reactions to the solvent. Abraxane doesn’t use a solvent. Instead, it wraps the main ingredient in albumin, the main protein of human blood plasma. So Abraxane can be easier to tolerate, and people getting Abraxane don’t need to take another medicine before receiving it.
Ixempra is a type of chemotherapy medicine called an epothilone. Ixempra works much like the taxanes, by interfering with how cancer cells divide and multiply. Research has shown that advanced-stage breast cancers that weren’t responding to standard chemotherapy treatments had a better response when Ixempra was used. Compared to Xeloda (chemical name: capecitabine) alone, giving Ixempra with Xeloda stopped advanced-stage cancer growing longer.
In this study, the researchers randomly assigned 783 women diagnosed with advanced-stage breast cancer (either stage IIIC or stage IV) that hadn’t been treated with chemotherapy yet to one of three treatments:
- Taxol once a week (275 women)
- Abraxane once a week (267 women)
- Ixempra once a week (241 women)
All three medicines were given in combination with Avastin (chemical name: bevacizumab). Avastin is a targeted therapy that was approved by the U.S. Food and Drug Administration (FDA) to be used in combination with Taxol to treat metastatic, HER2-negative breast cancer that hadn’t yet been treated with chemotherapy. When this study started in 2008, doctors hoped that Avastin would be an effective breast cancer treatment. But later research showed that Avastin offered only modest benefits for breast cancer, and in 2011, the FDA removed the breast cancer indication from Avastin. Still, many doctors continue to use it off-label, prescribing it to women diagnosed with breast cancer if they think the medicine will offer benefits.
Most of the cancers were hormone-receptor-positive:
- 72% of the cancers were hormone-receptor-positive
- 25% were triple negative (estrogen-receptor-negative, progesterone-receptor-negative, and HER2-negative)
- 2% were HER2-positive
The women were followed for lengths of time from about 2 years to more than 4 years.
The researchers wanted to know if one of the medicines would improve progression-free survival more than the others. Progression-free survival is how long a woman lives without the cancer growing.
The results showed that women who were treated with Taxol had the longest progression-free survival time. Progression-free survival time was:
- 11 months for Taxol
- 7.4 months for Ixempra
- 9.3 months for Abraxane
All three medicines can cause side effects, some of them serious, including anemia (low red blood cell counts), neutropenia (low white blood cell counts), neuropathy, fatigue, high blood pressure, pain, and nausea. Anemia and neutropenia are called hematologic side effects because they involve blood counts. The other side effects are called nonhematologic side effects because they don’t involve blood counts.
In this study, a larger percentage of women treated with Abraxane had serious side effects:
- 55% of women getting Abraxane had anemia or neutropenia
- 22% of women getting Taxol had anemia or neutropenia
- 12% of women getting Ixempra had anemia or neutropenia
- 65% of women getting Abraxane had a serious nonhematologic side effect
- 58% of women getting Ixempra had a serious nonhematologic side effect
- 49% of women getting Taxol had a serious nonhematologic side effect
The researchers recommended that Taxol once a week remain the standard chemotherapy treatment for women diagnosed with advanced-stage breast cancer that hasn’t been treated with chemotherapy yet.
Hope Rugo, M.D., clinical professor of medicine at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, was the lead author of the study. Dr. Rugo also is a member of the Breastcancer.org Professional Advisory Board.
Other authors who are members of the Breastcancer.org Professional Advisory Board are Clifford Hudis, M.D., chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center; Edith Perez, M.D., professor of medicine at Mayo Medical School; and Eric Winer, M.D., director of the breast oncology center at Dana-Farber Cancer Institute’s Gillette Centers for Women’s Cancers.
“In summary, this phase III cooperative group trial failed to demonstrate superiority of either nab-paclitaxel or ixabepilone given once per week compared with paclitaxel in patients with advanced [breast cancer], with all drugs given in combination with bevacizumab,” Dr. Rugo and her colleagues wrote. “Both newer agents were associated with increased overall toxicity, possibly inferior effectiveness, and reduced palliation of disease-related symptoms, even though earlier studies had suggested that either of the investigational arms, particularly nab-paclitaxel, might be more efficacious than standard once-per-week paclitaxel. On the basis of our data, once-per-week paclitaxel should remain the preferred microtubule inhibitor for treating patients with metastatic [breast cancer] in the first-line setting, and there is no evidence that either of the newer agents is superior.”
If you’ve been diagnosed with advanced-stage breast cancer, you and your doctor will discuss a number of treatment options, including chemotherapy and possible hormonal therapy (if the breast cancer is hormone-receptor-positive) and targeted therapy. If you haven’t been treated with chemotherapy yet, you might want to talk to your doctor about this study and ask if Taxol might be a good first chemotherapy choice for you, depending on your unique situation. Together, you and your doctor will decide on a treatment plan that’s best for you.
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