Reduction of paclitaxel-induced peripheral neuropathy with glutamine

L. Vahdat, K. Papadopoulos, D. Lange, S. Leuin, E. Kaufman, D. Donovan, D. Frederick, E. Bagiella, A. Tiersten, G. Nichols, T. Garrett, D. Savage, K. Antman, C. S. Hesdorffer, C. Balmaceda

Research output: Contribution to journalArticle

Abstract

Purpose: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose pachtaxel. Experimental Design: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m2 given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. Results: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P ≤ 0.05). The degree and incidence of motor weakness was reduced (56 versus 25%; P = 0.04) as well as deterioration in gait (85 versus 45%; P = 0.016) and interference with activities of daily living (85 versus 27%; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42% and 64 versus 50%, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. Conclusions: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity.

Original languageEnglish (US)
Pages (from-to)1192-1197
Number of pages6
JournalClinical Cancer Research
Volume7
Issue number5
StatePublished - 2001
Externally publishedYes

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Peripheral Nervous System Diseases
Paclitaxel
Glutamine
Paresthesia
Toes
Fingers
Hypesthesia
Neural Conduction
Activities of Daily Living
Gait
Research Design
Randomized Controlled Trials
Placebos
Breast Neoplasms
Drug Therapy
Incidence
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vahdat, L., Papadopoulos, K., Lange, D., Leuin, S., Kaufman, E., Donovan, D., ... Balmaceda, C. (2001). Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clinical Cancer Research, 7(5), 1192-1197.

Reduction of paclitaxel-induced peripheral neuropathy with glutamine. / Vahdat, L.; Papadopoulos, K.; Lange, D.; Leuin, S.; Kaufman, E.; Donovan, D.; Frederick, D.; Bagiella, E.; Tiersten, A.; Nichols, G.; Garrett, T.; Savage, D.; Antman, K.; Hesdorffer, C. S.; Balmaceda, C.

In: Clinical Cancer Research, Vol. 7, No. 5, 2001, p. 1192-1197.

Research output: Contribution to journalArticle

Vahdat, L, Papadopoulos, K, Lange, D, Leuin, S, Kaufman, E, Donovan, D, Frederick, D, Bagiella, E, Tiersten, A, Nichols, G, Garrett, T, Savage, D, Antman, K, Hesdorffer, CS & Balmaceda, C 2001, 'Reduction of paclitaxel-induced peripheral neuropathy with glutamine', Clinical Cancer Research, vol. 7, no. 5, pp. 1192-1197.
Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D et al. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clinical Cancer Research. 2001;7(5):1192-1197.
Vahdat, L. ; Papadopoulos, K. ; Lange, D. ; Leuin, S. ; Kaufman, E. ; Donovan, D. ; Frederick, D. ; Bagiella, E. ; Tiersten, A. ; Nichols, G. ; Garrett, T. ; Savage, D. ; Antman, K. ; Hesdorffer, C. S. ; Balmaceda, C. / Reduction of paclitaxel-induced peripheral neuropathy with glutamine. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 5. pp. 1192-1197.
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abstract = "Purpose: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose pachtaxel. Experimental Design: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m2 given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. Results: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P ≤ 0.05). The degree and incidence of motor weakness was reduced (56 versus 25{\%}; P = 0.04) as well as deterioration in gait (85 versus 45{\%}; P = 0.016) and interference with activities of daily living (85 versus 27{\%}; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42{\%} and 64 versus 50{\%}, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. Conclusions: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity.",
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T1 - Reduction of paclitaxel-induced peripheral neuropathy with glutamine

AU - Vahdat, L.

AU - Papadopoulos, K.

AU - Lange, D.

AU - Leuin, S.

AU - Kaufman, E.

AU - Donovan, D.

AU - Frederick, D.

AU - Bagiella, E.

AU - Tiersten, A.

AU - Nichols, G.

AU - Garrett, T.

AU - Savage, D.

AU - Antman, K.

AU - Hesdorffer, C. S.

AU - Balmaceda, C.

PY - 2001

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N2 - Purpose: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose pachtaxel. Experimental Design: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m2 given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. Results: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P ≤ 0.05). The degree and incidence of motor weakness was reduced (56 versus 25%; P = 0.04) as well as deterioration in gait (85 versus 45%; P = 0.016) and interference with activities of daily living (85 versus 27%; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42% and 64 versus 50%, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. Conclusions: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity.

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