Adjuvant chemotherapy is chemotherapy given after surgery to lower the risk of the cancer coming back (recurrence). The study reviewed here looked at women diagnosed with early-stage breast cancer and found that adjuvant chemotherapy regimens that included Xeloda (chemical name: capecitabine) reduced the risk of recurrence more than regimens that didn't include Xeloda. Still, Xeloda caused more serious side effects and increased the risk that chemotherapy might be stopped because of side effects.
Xeloda is used to treat advanced-stage breast cancer. It's not typically used to treat early-stage breast cancer and is not approved by the U.S. Food and Drug Administration to be used that way. But because Xeloda can help treat advanced-stage breast cancer, researchers wanted to know if adding Xeloda to a chemotherapy regimen might help reduce the risk of recurrence in women diagnosed with early-stage breast cancer. Xeloda is a pill taken by mouth.
In this Finnish study, 1,500 women diagnosed with early-stage breast cancer were split into two groups:
The women were followed for almost 3 years after diagnosis.
Most women -- no matter which group they were in -- didn't have a recurrence during the nearly 3 years of follow-up, but the women who got Xeloda had a better chance of not having a recurrence:
Still, the women who got Xeloda were more likely to have some serious side effects:
Some chemotherapy medicines, especially Xeloda, may cause hand-foot syndrome. Hand-foot syndrome happens when a small amount of medicine leaks out of the capillaries (small blood vessels), usually on the palms of the hands and soles of the feet. The medicine that has leaked out can damage the surrounding tissues. Hand-foot syndrome can be painful and can affect daily living. Symptoms include:
In severe cases, hand-foot syndrome can cause:
In this study, 24% of the women who got Xeloda stopped adjuvant chemotherapy treatment because of treatment-related side effects such as hand-foot syndrome. Only 3% of the women who didn't get Xeloda stopped chemotherapy because of side effects.
If you've been diagnosed with early-stage breast cancer, you and your doctor will discuss whether chemotherapy after surgery makes sense for you based on the details of the cancer and your unique situation. If adjuvant chemotherapy will be part of your treatment, your doctor will consider several chemotherapy regimens that have been shown to lower the risk of recurrence. This study suggests a regimen with Xeloda may have some promise. Still, the risk of serious side effects with Xeloda may outweigh its benefits. More research is needed before doctors know for certain if Xeloda is a good treatment for early-stage breast cancer.
You can learn more about chemotherapy and possible side effects in the Breastcancer.org Chemotherapy section.
Adding capecitabine (Xeloda) to standard adjuvant chemotherapy significantly reduced the risk of breast cancer recurrence, but the cost was a substantial increase in adverse events, investigators in a randomized clinical trial reported.
Three-year recurrence-free survival improved to 93% with capecitabine, compared with 89% for the standard regimen, the authors wrote online in The Lancet Oncology.
However, severe diarrhea and hand-foot syndrome occurred substantially more often with the capecitabine regimen, and eight times as many patients in the capecitabine arm discontinued therapy because of adverse effects.
"Our results suggest that integration of capecitabine upfront with potentially synergistic chemotherapeutic agents and into several cycles might be an effective treatment strategy," Heikki Joensuu, MD, of Helsinki University in Finland, and colleagues concluded.
"Integration of capecitabine was associated with frequent discontinuation of chemotherapy, but most patients could tolerate all six scheduled cycles," they added.
Patients with early breast cancer often received adjuvant therapy containing some combination of an alkylating agent, an anthracycline, and a taxane.
The addition of a taxane to an anthracycline improved disease-free and overall survival, but many patients still succumb to breast cancer, indicating a need for more effective therapy, the authors noted.
Capecitabine is a prodrug of fluorouracil, and the final step in the conversion to fluorouracil is catalyzed by thymidine phosphorylase, which is elevated in breast tumors.
Taxanes and cyclophosphamide increased tumor concentrations of thymidine phosphorylase in preclinical models, suggesting that administration with capecitabine would enhance the enzyme's activity in tumors and might produce anticancer synergy.
Investigators tested the synergy hypothesis in an open-label, randomized clinical trial involving 1,500 women with node-positive or high-risk node-negative breast cancer.
To increase exposure to the chemotherapy and possible eradication of cells that have slow cell-proliferation rates, patients received a total of 18 weeks of chemotherapy.
Patients were randomized to adjuvant chemotherapy regimens that were similar except for inclusion of capecitabine.
Half of the patients began therapy with capecitabine and docetaxel followed by cyclophosphamide, epirubicin, and capecitabine, while the remaining patients received docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil.
The primary endpoint was recurrence-free survival.
After a median follow-up of 35 months, the capecitabine regimen had led to a 4% absolute improvement in recurrence-free survival, which translated into a hazard ratio of 0.66 in favor of the capecitabine regimen (95% CI 0.47-0.94, P=0.020).
Capecitabine was associated with twice as many cases of grade 3-4 diarrhea (6% versus 3%) and more than 10 times as many cases of grade 3-4 hand-foot syndrome (11% versus <1%).
The control regimen caused more grade 3-4 neutropenia (98% versus 86%) and febrile neutropenia (9% versus 4%). The authors reported that 24% of patients in the capecitabine arm discontinued treatment because of adverse effects, compared with 3% of the control group.
The improved recurrence-free survival with the capecitabine regimen, despite a high dropout rate, might represent validation of the preclinical evidence suggesting that docetaxel sensitizes cancer cells to capecitabine by increasing levels of thymidine phosphorylase, Ruth O'Regan, MD, of Emory University in Atlanta, wrote in an invited commentary.
The study represents another "one size fits all" approach to managing a condition that exhibits considerable molecular heterogeneity, O'Regan continued.
"It is naive to assume that the same therapy will be of equal benefit for all subtypes," she said.
Though not practice changing, the findings merit further assessment, O'Regan concluded. However, the considerable toxicity associated with adding capecitabine to standard chemotherapy could dampen enthusiasm for further investigation.
The study was supported by Roche, sanofi-aventis, AstraZeneca, and the Cancer Society of Finland.
Joensuu disclosed a relationship with sanofi-aventis.
Coauthor Pirkko-Liisa Kellokumpu-Lehtinin and Petri Bono disclosed relationships with Roche and sanofi-aventis.
Marjo Pajunen disclosed relationships with Roche and sanofi-aventis.
Paula Poikonen disclosed a relationship with Roche.
Primary source: The Lancet Oncology Source reference: Joensuu H et al. "Adjuvant capecitabine in combination with docetaxel and chyclophosphamide plus epirubicin for breast cancer: an open-label, randomized, controlled trial" Lancet Oncol 2009; DOI: 10.1016/S1470-2045(09)0307-9.
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