A randomized, double-blinded, placebo-controlled trial of oral alpha lipoic acid to prevent platinum-induced polyneuropathy.

Abstract

9010 Background: Platinum-induced peripheral neuropathy may cause pain, function loss, and can be a dose-limiting factor for cancer treatment. The neurotoxicity can be irreversible; therefore prevention of chemotherapy-induced neuropathy is necessary. Our aim is to determine if α-lipoic acid (ALA, thioctic acid) can prevent peripheral neuropathy for patients (pts) receiving platinum-containing chemotherapy. Methods: Adult cancer pts were randomized to receive either 600 mg ALA or placebo (2 large pills) three times a day for 24 weeks while receiving platinum-base chemotherapy. Neuropathy was measured by FACT/GOG-NTX score and NCI-CTC neurotoxicity grade. Results: Of 243 pts randomized, 121 pts (51%) completed treatment for 12 weeks and 84 pts (35%) for 24 weeks. Of these, 70 pts completed FACT/GOG-NTX assessments at baseline and at 24 weeks. At baseline, the ALA (n =122) and placebo (n =121) groups were comparable for age (55±11 vs. 57±12 years), gender (54% vs 52% male), prior platinum exposure, and FACT/GOG-NTX score. At 24 weeks, only 34 evaluable pts remained in the ALA group, and 36 in the placebo group (p= 0.75). Pill size and dose frequency were frequent concerns regarding adherence. No statistical difference was noted in dose intensity for the oxaliplatin arm of the ALA group and the placebo group (median of 765 mg/m2 vs. 1020 mg/m2, p=0.18). No significant differences were noted for either FACT/GOG-NTX scores (p=0.70), neurotoxicity (p=0.87), or best tumor responses between the 2 groups (p=0.85). Conclusions: Oral ALA 600 mg PO TID was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. Intense schedules of oral agents in the symptom/toxicity prevention setting created adherence challenges due to pill size and frequency of administration. Poor adherence might affect the power to detect ALA’s effectiveness in this trial. Innovative drug delivery and trial designs are needed to further explore alpha lipoic acid in the prevention and/or reduction of chemotherapy-induced neuropathy.