Adriamycin (chemical name: doxorubicin) and Ellence (chemical name: epirubicin) are both anthracyclines, a type of chemotherapy medicine. Anthracyclines often are used to treat advanced-stage breast cancer. But sometimes cancers don't respond to an anthracycline. The small study reviewed here suggests that breast cancer that is resistant to an anthracycline may respond to a combination of two other chemotherapies, Taxotere (chemical name: docetaxel) and Xeloda (chemical name: capecitabine).
This research was presented at the 2008 American Society of Clinical Oncology (ASCO) Breast Cancer Symposium.
There's really no agreement on the best treatment to use when breast cancer is resistant to an anthracycline. Other research has shown that Taxotere and Xeloda together could work better than Taxotere alone, but doctors were concerned about serious side effects when using the two medicines at the same time. So the researchers decided to study the combination.
The study included 47 women diagnosed with advanced-stage breast cancer. All the cancers had been treated with an anthracycline and either didn't respond or stopped responding to that treatment. The women then got low-dose Taxotere once a week and Xeloda once a day. Taxotere is given intravenously. Xeloda is a pill taken by mouth. If the first dose of Taxotere was tolerated well, the dose was increased later on for some of the women. All the women also took Celebrex (chemical name: celecoxib), an anti-inflammatory medicine to help reduce side effects.
Some of the women had to stop taking Taxotere and Xeloda because of serious side effects. The researchers were able to look at how 38 of the women responded to the treatment:
Side effects were common and included:
While many of the women got benefits from the combination of Taxotere and Xeloda, more research is needed to see if using targeted therapies such as Herceptin (chemical name: trastuzumab), Tykerb (chemical name: lapatinib), or Avastin (chemical name: bevacizumab) along with this chemotherapy combination might offer even more benefits.
If you're being treated for advanced-stage breast cancer that isn't responding or stopped responding to Adriamycin or Ellence, you might want to talk to your doctor about this study and whether the combination of Taxotere and Xeloda might be a good next step for you.
WASHINGTON (MedPage Today) -- For patients with anthracycline-resistant breast cancer, continuous treatment with weekly low-dose docetaxel (Taxotere) plus daily capecitabine (Xeloda) provided a clinical benefit greater than 40%.
A third of patients had objective responses and almost 10% had stable disease beyond six months, Scott D. Young, M.D., Ph.D., of the University of Ottawa, reported at the ASCO Breast Cancer Symposium. However, adding celecoxib (Celebrex) to the therapy provided no obvious benefit in the small study.
Fewer than 10% of patients had grade 3-4 hematologic toxicity, and no patient had grade 3-4 nonhematologic toxicity.
"Treatment given in this metronomic fashion is associated with significant anticancer activity and was well tolerated in this study," said Dr. Young. "The efficacy of this regimen may be underestimated, as our study design involved a two-step escalation of docetaxel. It is possible that some patients experienced early progression prior to receiving an adequate dose of this agent."
There's no consensus on optimal treatment of anthracycline-resistant breast cancer, Dr. Young noted. The combination of docetaxel and capecitabine has demonstrated a survival advantage compared with docetaxel alone, but is associated with significant toxicity, he said.
Metronomic dosing, the practice of administering small doses on a rapid cycle, has been shown to improve the therapeutic index of some drugs and might have antiangiogenic effects, he added.
So he and his colleagues enrolled 47 patients with HER2-negative, anthracycline-resistant/refractory breast cancer, either locally advanced or metastatic.
They began treatment with weekly docetaxel at a dose of 15 mg/m2 plus capecitabine 1,250 mg daily and celecoxib 200 mg twice daily.
The celecoxib was given in an attempt to enhance the other drugs' anticancer efficacy and to minimize toxicity, said Dr. Young.
After four weeks, the docetaxel dose could be increased to 20 mg/m2 weekly for patients who did not have grade 3-4 neutropenia. Escalation of the docetaxel dose to 25 mg/m2 was permissible at eight weeks.
The primary endpoint was clinical benefit, defined as the proportion of patients who had a complete or partial response or who had stable disease for at least six months.
Approximately three-fourths of the patients had the first dose escalation of docetaxel and about a third had the second dose escalation.
Of 38 patients evaluable for response, 13 (34%) had a partial response and three (8%) had prolonged stable disease, resulting in an overall clinical benefit of 42%.
The median time to progression for all evaluable patients was 15 weeks; it was 32 weeks in patients who achieved clinical benefit.
Hematologic toxicity included one case of febrile neutropenia.
The most common nonhematologic toxicities (all grades) were diarrhea (15%), hand-foot syndrome (13%), fatigue (13%), mucositis (9%), and vomiting (6%).
Eleven patients discontinued treatment because of toxicity.
"This particular dosing schedule for docetaxel and oral capecitabine should be examined further in clinical studies involving combination therapy with novel targeted therapies," said Dr. Young.
One or more investigators in the study reported receiving honoraria from sanofi-aventis, Pfizer, and Roche, research funding from Roche and Roche Canada, and other forms of remuneration from Roche Canada.
Primary source: ASCO Breast Cancer Symposium 2008 Source reference: Young SD, et al "Phase II clinical rial examining the activity of docetaxel and oral capecitabine given in metronomic fashion and concurrently with celecoxib in patients with anthracycline-resistant metastatic breast cancer" ASCO Breast 2008; Abstract 256.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
Learn more about our commitment to your privacy
© 2010 Breastcancer.org - All rights reserved.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
