Neuropathy Does Not Predict Chemotherapy Outcome
A retrospective analysis of 4,554 women treated with taxane-based chemotherapy found that though neuropathy is a common side effect, its presence does not predict better outcomes such as longer overall survival or lower risk of recurrence. Neuropathy is damage to the nervous system that causes pain, numbness, tingling or swelling of the hands or feet.
Study authors call for further research of DNA changes that may be related to neuropathy, to determine their use in treatment and dose decisions.
Doctors strive to balance the benefit of a medicine with the side effects it may cause, so that individuals get the best possible treatment with the least possible negative effects. Mild side effects can sometimes signal that an effective dose of a medicine is being given.
Investigators on this analysis explored whether moderate to very severe neuropathy caused by taxane-based chemotherapy predicted better treatment outcomes. The goal was to see whether women who developed neuropathy gained more from the treatment than those who did not.
They also considered whether single nucleotide polymorphisms (SNPs) that are believed to be associated with neuropathy may eventually play a role in making treatment decisions for breast cancer. SNPs are small changes in DNA coding that sometimes occur when DNA is copied during cell division, and are under study.
Records from the clinical trial E1199 were used. E1199 compared the effectiveness of two taxane-based chemotherapies, paclitaxel (Taxol) and docetaxel (Taxotere), and two treatment schedules – chemotherapy given once every three weeks for four cycles, versus given once a week for 12 cycles. All participants received four cycles of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) once every three weeks before taxane treatment. They were then assigned to four treatment arms and received:
- Paclitaxel given once every three weeks for four cycles (Arm I)
- Paclitaxel given once a week for 12 cycles (Arm II)
- Docetaxel given once every three weeks for four cycles (Arm III)
- Docetaxel given once a week for 12 cycles (Arm IV)
Only women who had neuropathy within seven months of starting the study treatment were included in this analysis. The researchers assessed overall survival, breast cancer-free survival and recurrence-free survival, along with participant characteristics including age, menopausal status, race and hyperglycemia, too much sugar in the blood that could suggest diabetes—a condition that also causes neuropathy.
The researchers found neuropathy was not associated with overall survival, breast cancer-free survival or recurrence-free survival overall, or when broken down by tumor type (ER/PR positive, HER2 positive, triple-negative). It was also not associated with survival outcomes when age, race, obesity, menopausal status, tumor size, lymph node involvement, hyperglycemia and treatment arm were considered. They also found:
- 770 (or 16 percent of) participants who had neuropathy reported it was moderate to very severe, with the highest number reporting moderate (71.8 percent) and lowest number reporting very severe (0.4 percent)
- The risk of neuropathy was greatest in Arm II (weekly paclitaxel) and lowest in Arm IV (weekly docetaxel)
- Premenopausal women had a lesser risk of neuropathy than postmenopausal women
What This Means For You
That neuropathy itself is not associated with survival outcomes means that having it does not predict the benefit of taxane-based chemotherapy. It may also reassure you to know that having neuropathy doesn’t necessarily mean your treatment is, or is not, working against the cancer. The researchers also note that another trial, E5103, showed that age may be associated neuropathy. More research needs to be done to determine the role of age in developing neuropathy.
The investigators believe more research needs to be done to accurately determine the SNPs related to neuropathy development. By identifying SNPs that predict neuropathy risk, doctors may eventually be able to prescribe taxane-based chemotherapy based on the likelihood of developing neuropathy, possibly saving future women from developing this difficult side effect.
Schnieder, Bryan P., Zhao, Fengmin, et al: Neuropathy Is Not Associated With Clinical Outcomes in Patients Receiving Adjuvant Taxane-Containing Therapy for Operable Breast Cancer. J Clin Oncol (September 2012) 30 (25): 3051- 57.