Long-term Peripheral Neuropathy in Breast Cancer Patients Treated With Adjuvant Chemotherapy: NRG Oncology/NSABP B-30

Abstract

Background: The long-term effects of chemotherapy are sparsely reported. Peripheral neuropathy (PN) is one of the most frequent toxicities associated with taxane use for the treatment of early-stage breast cancer. We investigated the impact of the three different docetaxel-based regimens and patient characteristics on long-term, patient-reported outcomes of PN and the impact of PN on long-term quality of life (QOL).

Methods: The National Surgical Adjuvant Breast and Bowel Project Protocol B-30 was a randomized trial comparing sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T) (AC→T), concurrent ACT, or AT in women with node-positive, early-stage breast cancer. The AC→T group had a higher cumulative dose of T. PN was one of the symptoms assessed in a QOL substudy. Statistical methods included simple and mixed ordinal logistic regression and general linear models. All statistical tests were two-sided.

Results: Of 1512 patients, 41.9% reported PN two years after treatment initiation. Treatment with AT and ACT was associated with less severe long-term PN compared with AC→T (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.35 to 0.58; OR = 0.59, 95% CI = 0.46 to 0.75). Preexisting PN, older age, obesity, mastectomy, and greater number of positive nodes were also associated with higher risk of long-term PN. Patients who reported worse PN symptoms at 24 months had statistically significantly worse QOL (Ptrend < .001).

Conclusions: The administration of docetaxel is associated with long-term PN. The lower rate of long-term PN in AT and ACT patients might be an important consideration in supporting choosing these therapies for individuals with preexisting neuropathic symptoms or other risk factors for neuropathy.

Trial registration: ClinicalTrials.gov NCT00003782.

Figure 1.

The severity of the peripheral neuropathy symptom by time and treatment as reported by patients enrolled in the NSABP B-30 Quality of Life substudy. Patients were asked to indicate how much they were bothered by numbness or tingling in hands or feet. Responses, based on a symptom experienced in the past seven days, were recorded on a five-point scale (from a “bother” rating of 0 = “not at all” to 4 = “very much”). A = doxorubicin; C = cyclophosphamide; T = docetaxel.

Figure 2.

Comparison of quality of life as measured by the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index (FACT-B-TOI) score at 24 months among patients reporting different levels of peripheral neuropathy (PN) symptom severity: NSABP B-30 Quality of Life Sub study. Patients were asked to indicate how much they were bothered by numbness or tingling in hands or feet. Responses, based on a symptom experienced in the past seven days, were recorded on a five-point scale (from a “bother” rating of 0 = “not at all” to 4 = “very much”). The ends of the whiskers in the box and whisker plots represent the minimum and maximum values of the group.