Neuropathy is a common and potentially disabling complication of adjuvant taxane therapy. Recent studies have identified candidate single nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we sought to determine whether neuropathy was associated with breast cancer recurrence in a clinical trial population who received adjuvant taxane therapy.
Trial E1199 included 4,554 eligible women with operable breast cancer who received up to four cycles of doxorubicin and cyclophosphamide every 3 weeks followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles (P3), paclitaxel 80 mg/m(2) weekly for 12 cycles (P1), docetaxel 100 mg/m(2) every 3 weeks for four cycles (D3), or docetaxel 35 mg/m(2) weekly for 12 cycles (D1). A Cox proportional hazards model was used to determine the relationship between neuropathy and disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) by treating neuropathy status as a time dependent covariate and using a landmark analysis.
Of 4,554 patients who received at least one taxane dose, grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and 13% of patients in the P3, P1, D3, and D1 arms, respectively. In a model that included age, race, obesity, menopausal status, tumor size, nodal status, treatment arm, neuropathy, and hyperglycemia, no significant relationship was found between neuropathy and DFS, OS, or RFS.
There was no association between taxane-induced neuropathy and outcome.
"CIPN remains an important toxicity of taxane administration. A recently published study demonstrated that CIPN, in and of itself, has no effect on disease free survival, progression free survival or overall survival (Schneider et al. 2012), however, the potential consequences of dose reduction as a result of CIPN on PFS and OS remain unknown. In its most severe form, CIPN greatly impairs quality of life and can potentially lead to secondary consequences such as increased risk of recurrent falls (Gewandter et al. 2013; Tofthagen et al. 2012). "
[Show abstract][Hide abstract] ABSTRACT: Purpose
Taxanes are a cornerstone treatment in early and advanced stage breast cancer and in other common solid tumor malignancies; however, the development of chemotherapy induced peripheral neuropathy (CIPN) often necessitates dose-reduction, which may hamper the effectiveness of the drug and compromise survival outcomes especially when used in the adjuvant setting. Limited literature is available on the prevalence and severity of dose reduction due to CIPN. We sought to determine the frequency and severity of CIPN-induced dose reduction in early stage breast cancer patients who received taxane-based chemotherapy in the neoadjuvant or adjuvant settings.
We conducted a retrospective single-institution breast cancer clinic chart review of 123 newly diagnosed breast cancer patients and treated with taxane-based neoadjuvant/adjuvant chemotherapy at the University of Maryland Greenebaum Cancer Center between January 2008 and December 2011.
Forty-nine of 123 (40%; 95% CI: 31-49%) patients required dose reduction. Twenty-one (17%; 95% CI: 11-25%) of these patients were dose-reduced specifically due to CIPN that developed during treatment. The median relative dose intensity (received dose/planned dose) for the 21 CIPN-induced dose reduction patients was 73.4% (range, 68.0-94.0%). Patients with diabetes appeared to have a higher risk of taxane-induced dose reduction (p-value=0.01). African-American patients and those treated with paclitaxel (rather than docetaxel) experienced a higher-risk of CIPN-induced dose reduction (p-values are <0.001 and 0.001, respectively).
The incidence of CIPN-associated dose reduction in our patient population was 17%. African-American patients, diabetics and subjects treated with paclitaxel had a higher risk for CIPN-associated dose reduction in our study.
[Show abstract][Hide abstract] ABSTRACT: Although considerable treatment advances have been made since the early 2000s, metastatic breast cancer (MBC) continues to provide challenges for patients and healthcare providers. The responsibilities of nurses regarding the management of MBC are extensive. Among other things, nurses must provide patient education, understand treatment administration, and have the ability to perform patient assessments, as well as identify and manage symptoms. The taxanes paclitaxel, docetaxel, and nab-paclitaxel are a class of microtubule-stabilizing agents that are highly active against MBC but have many differences among them (e.g., formulation, administration, efficacy, tolerability profiles). Understanding those differences will aid in improving the overall patient experience. This supplement provides a historical overview of taxanes, examines the differences in their administration, and defines their efficacy and safety profiles and effects on patient quality of life. In addition, methods for assessing taxane-induced neuropathy are discussed from the nursing perspective, and treatment considerations for older adult patients with MBC are provided.
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