The Functional Implications of Taxane-induced Neuropathy

Institution: University of California, San Francisco
Investigator(s): Meredith Edwards Wampler, B.H.S. -
Award Cycle: 2004 (Cycle 10) Grant #: 10GB-0001 Award: $33,937
Award Type: Dissertation Award
Research Priorities
Community Impact of Breast Cancer>Sociocultural, Behavioral, and Psychological Issues: the human side



Initial Award Abstract (2004)
Taxol (paclitaxel) and Taxotere (docetaxel) are effective chemotherapy drugs used in the treatment of breast cancer. These drugs kill cancer cells reducing the size of the tumor and preventing the spread of the disease to distant sites. Because the drugs are administered to the whole body, they unfortunately also affect non-cancerous cells. Nerve cells to the hands and feet are particularly susceptible to the effects of these drugs. As a result, many patients develop pain, decreased reflexes, and abnormal sensations of the hands and feet when taking Taxol or Taxotere. Patients with similar nerve problems due to other causes, such as diabetes, have been shown to have problems with pain, balance, arm function, physical performance, and decreased quality of life. However, it is unknown at this time if Taxol or Taxotere-induced changes to nerve cells has a similar impact in breast cancer patients.

Three questions will be answered during this study:
  1. Do women taking Taxol or Taxotere have increased problems with nerve function, balance, pain, arm function, physical performance and quality of life compared to healthy women of the same age and body type?
  2. What is the best clinical test to identify the severity of changes to nerve function in women taking Taxol or Taxotere as part of their treatment for breast cancer?
Are the severity of nerve changes, as measured by the best clinical test identified in question 2, related to problems with balance, pain, arm function, physical performance, and quality of life?

There will be two groups of women who participate in this study. The first group will include women who have completed their Taxol or Taxotere therapy for breast cancer. The second group will include healthy women of the same age and body type compared to the chemotherapy group. Six variables will be measured in this study: nerve function, balance, arm function, physical performance, pain, and quality of life. A clinical exam and nerve conduction studies (chemotherapy group only) will be used to quantify nerve function. The other variables will be measured through performance of balance tasks with eyes open and closed, moving your arm to and from a target with your eyes closed, timed short distance walking, and questionnaires. These tests will be performed in two two-hour sessions at the Mount Zion and Parnassus campuses of UCSF.

This study is unique because no one has investigated the impact Taxol and Taxotere have on the physical well-being and quality of life of women being treated for breast cancer. In addition to describing the problem, we will also identify the best clinical method to measure changes in nerve function due to Taxol and Taxotere therapy. This study will lay the foundation for future studies focused on the development of treatments for balance, pain, and arm function problems before they can have a detrimental impact on physical performance and quality of life. This will be a significant advancement in the quality of life for breast cancer patients during and after treatment.


Final Report (2006)
Up to 60% of people who take paclitaxel or docetaxel will develop peripheral neuropathy (PN)--a decreased function of the nerves to the arms and legs. Patients commonly complain of sensory symptoms including numbness, tingling, or burning pain of their hands and/or feet. In severe cases, muscle weakness has also been reported. Patients with PN due to diabetes mellitus have increased pain, decreased balance, and decreased quality of life (QOL). However, to date, an investigation of associations between taxane-induced PN and pain, balance, and QOL have not been reported. The goal of this project was to quantify the differences in PN, pain, balance, physical mobility, and QOL in women after they completed taxane chemotherapy compared to healthy women. A second goal of this project was to identify a clinically feaseible and valid measure of taxane-induced PN that correlated with impairments in balance, physical performance, pain, and QOL.

All goals of this study have been achieved. There were 20 women with breast cancer and 20 healthy women matched on age, height, and weight who participated in this project. Women in the breast cancer group were found to have statistically signficant PN, impaired balance, impaired physical mobility, and decreased QOL compared to the women in the healthy group (p < .05). Pain was not universally experienced by the women in the breast cancer group. While 70% of the women reported pain, unfortunately, only 45% were receiving analgesics. The second goal was achieved through correlational analysis comparing several clinical measures of PN to a gold standard measure of PN, the Total Neuropathy Score (TNS). In this analysis, the Modified Total Neuropathy Score (mTNS) was found to be the most highly correlated at .990 (p < .001) to the TNS. In addition, the mTNS was found to be moderately correlated to changes in balance, physical mobility and QOL (p < .05). No measures of pain were significantly correlated with any measure of PN.

Patients with breast cancer who have completed taxane chemotherapy may present with PN, impaired balance, impaired physical mobility, and decreased QOL. In addition, some women may present with a painful PN. The mTNS may be a valid and clinically feasible measure of taxane-induced PN in women with breast cancer. It is highly correlated to a gold standard measure of PN, yet is less expensive and more easily tolerated because nerve conduction studies are eliminated. In addition the mTNS is correlated with changes in balance, physical performance, and QOL. Therefore, oncology clinicians may be able to use the mTNS to identify patients who may benefit from physical therapy services for assessment and treatment of balance and physical mobility. However, because pain was not correlated to any measure of PN, pain may need to be assessed seperately to identify patients who may benefit from treatment of taxane-induced neuropathic pain.


Symposium Abstract (2005)
*Edwards (Wampler), Meredith PT, DPTSc Candidate, Hamel, Kathryn A., PhD, Topp, Kimberly S., PT, PhD * Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, and San Francisco State University, Box 0736, San Francisco,CA 94143-0736; e-mail: medwards@itsa.ucsf.edu

Up to 60% of people who take paclitaxel or docetaxel, drugs from the taxane class of chemotherapy agents, will develop peripheral neuropathy (PN)—a decreased function of the nerves to the arms and legs (1, 2). Patients commonly complain of sensory symptoms including numbness, tingling, or burning pain of their hands and/or feet. In severe cases, muscle weakness has also been reported (3, 4). Patients with PN due to diabetes mellitus have increased pain, decreased balance, and decreased quality of life (QOL) (5, 6). However, to date, an investigation of associations between taxane-induced PN and pain, balance, and QOL have not been reported. The goal of this research project is to quantify the differences in PN, pain, balance, and QOL in women after they have completed taxane chemotherapy compared to healthy women of the same age, height, and weight. A second goal of this project is to identify a clinical tool to measure PN that is associated with pain, balance, and QOL. This type of tool could help health care providers identify women who may benefit from a referral to a physical therapist for balance assessment and retraining and to a pain clinic for neuropathic pain management.

To date, 17 women with breast cancer (BC) (48.5±8.7 years) and 11 healthy women (C) (49.6±7.8 years) have participated in our project. The following measures were significantly different between BC and C groups (p<.05): Peripheral neuropathy--Michigan Diabetic Neuropathy Score (MDNS), Modified Total Neuropathy Score (mTNS), vibration threshold at the great toe and head of the ulna, and touch thresholds of the index finger; Balance measures-- Sensory Organization Test (SOT), center of pressure velocity in four positions on a static force plate, Fullerton Advanced Balance Scale (FABS); Pain measures—pain below the knee; QOL—Functional Assessment Cancer Therapy-Trial Outcome Index (FACT-TOI).

The mTNS significantly correlated (p<.05) with the TNS, MDNS, SOT, three force plate measures, FABS, and FACT-TOI. Vibration threshold of the great toe significantly correlated (p<.05) with two force plate measures only. The MDNS and touch thresholds were not significantly correlated with balance, pain, or QOL measures. Pain below the knee and below the elbow was not significantly correlated with any measure of PN.

Patients with breast cancer who have undergone taxane chemotherapy treatment have a statistically significant increase in peripheral neuropathy compared to healthy women. In addition, they demonstrate decreased balance, increased pain below the knee, and decreased quality of life compared to healthy women. The mTNS test may be the best clinical measure of taxane-induced peripheral neuropathy given its consistent association with measures of balance and quality of life. The mTNS could be used by health care providers to determine if patients would benefit from physical therapy to improve balance. As pain is significantly increased in the group of women with breast cancer but not significantly associated with peripheral neuropathy measures, it may be important to use a separate measure of pain to determine if women would benefit from a pain management regimen.

References 1. Taxol Prescribing Information. Bristol Meyers Squibb. Available at: http://www.accessdata.fda.gov/scripts/cder/onctools/labels.cfm?GN=paclitaxel. Accessed April 13, 2005. 2. Taxotere Prescribing Information. Aventis. Available at: http://www.aventis-us.com/PIs/taxotere_TXT.html. Accessed April 13, 2005. 3. Lipton RB, Apfel SC, Dutcher JP et al. Taxol produces a predominantly sensory neuropathy. Neurology 1989; 39:368-73. 4. Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol 1994; 35:304-11. 5. Simoneau GG, Ulbrecht JS, Derr JA, Becker MB, Cavanagh PR. Postural instability in patients with diabetic sensory neuropathy. Diabetes Care 1994; 17:1411-21. 6. Galer BS, Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain