Glutathione Protects Against Oxaliplatin Neurotoxicity

Laurie Barclay, MD

August 22, 2002

Aug. 23, 2002 — Glutathione may protect against the neurotoxicity of oxaliplatin, a relatively new chemotherapeutic used in the treatment of colorectal and other cancers, according to the results of a randomized controlled trial reported in the Aug. 15 issue of the Journal of Clinical Oncology. Even better, this inexpensive drug does not adversely affect the efficacy of oxaliplatin.

"An optimal strategy for reducing the neurotoxicity associated with oxaliplatin may be the use of agents such as glutathione, which may be able to prevent the initial accumulation of platinum adducts in dorsal root ganglia," write Stefano Cascinu, MD, and colleagues from the Universitaria di Parma in Italy. "The lack of toxicity and interference with oxaliplatin activity, as well as its low economic cost, makes glutathione an ideal new drug for the prevention of oxaliplatin-induced neuropathy in colorectal cancer patients."

In this double-blind trial, 52 patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive glutathione, 1,500 mg/m2, or normal saline solution infused over 15 minutes before oxaliplatin administration.

After the fourth treatment cycle (oxaliplatin dose, 400 mg/m2), seven patients receiving glutathione and 11 patients receiving placebo had clinically evident neuropathy. After the eighth cycle (oxaliplatin dose, 800 mg/m2), nine of 21 assessable patients receiving glutathione and 15 of 19 receiving placebo had neurotoxicity. Only two patients receiving glutathione treatment met grade 2 to 4 National Cancer Institute common toxicity criteria for neuropathy compared with 11 patients receiving placebo (P=.003). After 12 cycles (oxaliplatin dose, 1200 mg/m2), three patients receiving glutathione and eight patients receiving placebo had grade 2 to 4 neurotoxicity (P=.004).

Sural sensory nerve conduction was significantly decreased in the placebo group but not in the glutathione group. The response rate was 26.9% in the glutathione group and 23.1% in the placebo group, indicating no reduction by glutathione of oxaliplatin efficacy.

"These findings may have important clinical implications. In several cases, despite good clinical activity, treatment with oxaliplatin must be discontinued because of the onset of neurotoxicity," the authors write, noting expanding use of oxaliplatin in several other cancers as well as in the adjuvant setting. "The concomitant use of glutathione may allow the administration of an effective treatment for a more prolonged time. In fact, in the placebo arm, none of the patients could receive further oxaliplatin treatment because of the development of neurotoxicity; in the glutathione arm, seven patients did not develop any sign of clinical neurotoxicity and could continue on treatment."

J Clin Oncol. 2002;20(16):3478-3483

Reviewed by Gary D. Vogin, MD

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