Chemotherapy-induced peripheral neuropathy is nerve damage caused by cancer drugs. A Cochrane review notes that most patients who complete a full course of cisplatin develop a detectable sensory neuropathy [6].
Glutathione is an antioxidant made in the body, and it was tested for decades as a way to shield nerves during platinum chemotherapy. This page sets out what those trials measured, and where the evidence split. How glutathione is given in other settings is covered in glutathione injections.
The cisplatin trials
A 1995 double-blind trial enrolled 50 patients with advanced stomach cancer on weekly cisplatin [1]. The glutathione arm received 1.5 g/m² by vein over 15 minutes before cisplatin, then 600 mg by intramuscular injection on days 2 to 5.
After 15 weeks, 4 of 24 assessable patients on glutathione had nerve damage, against 16 of 18 on placebo (P = .0001). Tumor response was 76% with glutathione and 52% with placebo, which the authors read as no loss of chemotherapy activity.
A 1997 double-blind trial enrolled 151 women with ovarian cancer on cisplatin at 100 mg/m² [2]. Its main question was whether more women could finish six full cycles.
With glutathione, 58% received six courses, against 39% without it (P = 0.04). Quality-of-life scores favored glutathione for several symptoms, including peripheral neurotoxicity. Response was 73% versus 62%, which was not statistically significant.
The oxaliplatin trials
A 2002 double-blind trial enrolled 52 patients with advanced colorectal cancer on oxaliplatin [3]. The glutathione arm received 1,500 mg/m² by vein over 15 minutes before each oxaliplatin dose.
After 12 cycles, grade 2 to 4 nerve damage affected 3 patients on glutathione and 8 on placebo (P = .004). Response rates were 26.9% and 23.1%, so the authors found no loss of oxaliplatin’s activity.
A 2009 trial randomized 27 patients receiving oxaliplatin-based adjuvant treatment for colorectal cancer [4]. Glutathione at 1,500 mg/m² reduced nerve damage by the end of treatment (P = 0.0037). Platinum bound to DNA in white blood cells did not differ between arms.
One measure did change. Total platinum exposure in the blood was lower with glutathione, which the authors put down to glutathione’s role in clearing oxaliplatin and removing platinum bound to plasma proteins.
The larger trial that found nothing
The largest test came from a US cooperative group, reported in 2014 [5]. It randomized 185 patients on paclitaxel and carboplatin to 1.5 g/m² glutathione (n = 94) or placebo (n = 91), infused over 15 minutes before chemotherapy.
Nerve damage did not differ between arms on either the patient questionnaire (P = .21) or clinician grading (P = .449). Time to grade 2 or worse neuropathy favored placebo (P = .039). The authors concluded their results do not support glutathione for this purpose.
This trial used a different drug pairing. Paclitaxel is a taxane, a different class from the platinum drugs in the earlier trials, and carboplatin was not tested in them. The negative result may not transfer to cisplatin or oxaliplatin, and the positive results may not transfer to it.
| Trial | Patients and chemotherapy | Glutathione given | Nerve result |
|---|---|---|---|
| 1995, stomach cancer | 50, weekly cisplatin | 1.5 g/m² IV, then 600 mg IM | 4 of 24 vs 16 of 18 at week 15 |
| 1997, ovarian cancer | 151, cisplatin 100 mg/m² | Abstract gives no dose | Better neurotoxicity scores |
| 2002, colorectal cancer | 52, oxaliplatin | 1,500 mg/m² IV | Grade 2–4: 3 vs 8 after 12 cycles |
| 2009, colorectal cancer | 27, oxaliplatin (FOLFOX4) | 1,500 mg/m² IV | Less neurotoxicity, P = 0.0037 |
| 2014, phase 3 | 185, paclitaxel and carboplatin | 1.5 g/m² IV | No difference |
What the pooled evidence says
A 2014 Cochrane review looked at agents tested to prevent nerve damage from cisplatin and related drugs [6]. It included seven glutathione trials with 387 participants.
On clinician grading of grade 2 or worse neuropathy, glutathione cut the risk: risk ratio 0.29 (95% CI 0.10 to 0.85). Only one glutathione trial used quantitative sensory testing, the review’s primary outcome, and it reported only qualitative analyses.
The reviewers called the result modest but promising and borderline significant. They concluded the data were insufficient to say any agent prevents platinum nerve damage on objective measures.
What the cancer guidelines say
The American Society of Clinical Oncology reviewed 48 randomized trials for its 2014 guideline [7]. Given the paucity of high-quality, consistent evidence, it recommended no agents for preventing chemotherapy nerve damage.
The 2020 update added 28 prevention trials and three systematic reviews [8]. It reconfirmed that no agents are recommended for prevention. Its advice for intolerable neuropathy is to consider delaying, reducing, substituting or stopping the chemotherapy.
What this means
Glutathione before platinum chemotherapy looked protective in small trials, and pooled clinician grading agrees. The one large trial, on a different regimen, found nothing, and both ASCO guidelines recommend no preventive agent.
Reported reactions to glutathione are in glutathione side effects, and amounts used in other studies are in glutathione dosage. For the wider picture, see the longevity goal page.