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, 1192–1197.

Female participants were were admitted for cyclophosphamide (6,000 mg/m²), thiotepa (500 mg/m²) and carboplatin (800 mg/m²) over 96 hours seven and four days prior to stem cell transplantation. Mesna (7,400 mg/m²; 1,500 mg/m² per day) was administered by continuous infusion over 120 hours. After December 1998, women enrolled in the study received glutamine (10 g orally three times daily) for four days starting 24 hours after the completion of paclitaxel. Data were collected at baseline and two weeks after completion of chemotherapy. In addition, paired pre- and post-paclitaxel evaluations were performed on all women.

• The study had a sample size of 45 women with advanced breast cancer, 12 who received glutamine 10 g orally three times daily for four days starting 24 hours after the completion of paclitaxel, and 33 women placed in the historical comparison group.
• Women were eligible to participate they were to receive high-dose chemotherapy (paclitaxel 825 mg/m² via continuous infusion over 24 hours four days before transplantation and melphalan 90 mg/m² per day for two consecutive days after recovery) with stem cell support.
• Women with stage IV breast cancer also were eligible if their disease had responded (partial or complete response) to conventional dose chemotherapy.
• Those with central nervous system metastases, prior progression while on a taxane, compromised organ function, or baseline neuropathy from chemotherapy that was disabling were excluded.

• A detailed neurologic history and neuropathy assessment instrument was used.
• Questions assessing symptoms were asked separately for fingers and toes and were graded as mild, moderate, or severe as well as their interference with functioning.
• Evaluation of reflexes, vibration sense, pin prick, and proprioception were performed on upper and lower extremities.
• Cerebellar function, gait, and motor weakness also were evaluated.
• Nerve conduction studies were performed in four nerves, with motor responses recorded.
• Serial sensory nerve conduction studies were performed on three nerves.

Women who received glutamine had fewer symptoms, with 8% of women who received glutamine reporting dysesthesias in the fingers and toes, as compared to 40% of the women who did not receive glutamine. In addition, the frequency of moderate to severe numbness was observed less often in the glutamine-treated group than in the non-glutamine group for both fingers and toes. Moderate to severe parasthesias also were observed less frequently in those who received glutamine.

• A non-randomized design.
• Unbalanced treatment and comparison groups.
• The grading of myalgias was not collected prospectively.
• Retrospective chart reviews were performed.
• Neurologic examinations can vary in their findings, even when performed by one examiner.