Taxane Neuropathy Not Linked to Breast Cancer Outcomes

Janis C. Kelly

September 14, 2011

September 14, 2011 — Data from nearly 5000 women treated with taxane regimens for breast cancer show that development of taxane-induced neuropathy does not contribute to better survival. The new finding largely answers questions raised by previous studies in which treatment-induced side effects appeared to predict better outcomes, said Bryan P. Schneider, MD, who reported the study at the 2011 Breast Cancer Symposium in San Francisco.

"Neuropathy of grades 2-4 did not affect recurrence-free survival, disease-free survival, or overall survival in any breast cancer subtype or for any of the 4 regimens used," said Dr. Schneider, who is associate professor of medicine and associate director of the Indiana Institute for Personalized Medicine at Indiana University's Simon Cancer Center in Indianapolis.

Dr. Schneider and colleagues analyzed data from the E-1199 study, which included 4950 women with axillary lymph node–positive or high-risk lymph node–negative breast cancer who received up to 4 cycles of doxorubicin/cyclophosphamide every 3 weeks, followed by paclitaxel, 175 mg/m2 every 3 weeks x 4; paclitaxel, 80 mg/m2 weekly x 12; docetaxel, 100 mg/m2 every 3 weeks x 4; or docetaxel, 35 mg/m2 weekly x 12. The findings are based on the 4702 women who received at least 1 taxane dose.

Grade 2-4 neuropathy rates ranged from 20% and 27% in the paclitaxel groups and 16% in both of the docetaxel groups.

The researchers reported, "In a model including age, tumor size, nodal status, treatment arm, neuropathy, and the neuropathy-treatment interaction, there was no relationship between neuropathy and [disease-free survival] and [overall survival] in the entire population, for any of the individual treatment arms, or for any breast cancer subtypes, whether analyzed as a time-dependent covariate or using a landmark analysis."

Neuropathy rates were higher in black patients (25% vs. 19%; P = .02) and in obese patients (21% vs. 19%; P = .04) but did not vary with age. There was also a suggestion of higher neuropathy risk for patients whose blood glucose rose during treatment, which might be an indication of diabetes or prediabetes, said Dr. Schneider.

SNPs May Aid in Patient Selection for Taxanes

The researchers concluded that because taxane-induced neuropathy is not associated with outcome, "validation of SNPs [single nucleotide polymorphisms] predictive of neuropathy may be useful in identifying patients at higher risk for neuropathy but not taxane benefit, and thereby improve therapeutic individualization."

An American expert at the meeting echoed this comment about the potential of SNPs.

"As components of adjuvant chemotherapy, taxanes improve relapse-free and overall survival. Their use can be limited by peripheral neuropathy. Prior work has demonstrated the potential for single nucleotide polymorphisms to predict for taxane neurotoxicity," said Andrew Seidman, MD, from the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City. He is also a member of the 2011 Breast Cancer Symposium News Planning Team.

Dr. Seidman also reiterated the study's major findings. "The current analysis, derived from ECOG [European Clinical Oncology Group] 1199 provides reassurance that taxane neuropathy is not linked to taxane benefit," he said.

The researchers suspect that the genetic marker RWDD3 will emerge as one of the biomarkers for susceptibility to taxane neuropathy. Dr. Schneider said that it helps stabilize cells during times of stress and that alterations in this gene might make patients' nerve cells more fragile during the stress of taxane treatment.

"We are looking forward to a time when we can look at the tumor and know what drugs are likely to be effective against it, and look at the patient and know which drugs are likely to cause side effects for her. Between the 2, we will be able to say, 'Here is our best approach to therapy for you,' " Dr. Schneider told Medscape Medical News.

Dr. Schneider and Dr. Seidman have disclosed no relevant financial relationships.

2011 Breast Cancer Symposium. Abstract #270. Presented September 8, 2011.


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