Interventions for preventing neuropathy caused by cisplatin and related compounds.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 24687190 · doi:10.1002/14651858.CD005228.pub4
What was done
This Cochrane systematic review searched multiple databases through March 2013 for randomized or quasi-randomized controlled trials evaluating chemoprotective agents (including amifostine, calcium/magnesium, glutathione, Org 2766, vitamin E, acetylcysteine, diethyldithiocarbamate, oxcarbazepine, and retinoic acid) compared with placebo, no treatment, or active comparators in patients receiving cisplatin or related chemotherapy. The primary outcome was quantitative sensory testing (QST) evaluated zero to six months post-chemotherapy; secondary outcomes included nerve conduction studies and validated clinical toxicity scales such as the National Cancer Institute Common Toxicity Criteria (NCI-CTC).
What was found
The review included 29 trials with 2,906 participants. Only seven trials reported primary QST data and nine reported nerve conduction test results. In secondary subjective outcomes, amifostine significantly reduced the risk of developing NCI-CTC grade ≥ 2 neurotoxicity compared to placebo (RR 0.26, 95% CI 0.11 to 0.61; 15 pooled trials for NCI-CTC), as did glutathione (RR 0.29, 95% CI 0.10 to 0.85). Three vitamin E trials each favoured the intervention on subjective non-pooled measures. Adverse effects included transient hypotension with amifostine (8% to 62%), hypocalcemia with retinoic acid (11%), and toxic withdrawals with diethyldithiocarbamate (~20%).
Why it matters
Despite promising subjective symptom reductions with agents such as amifostine and glutathione, there remains insufficient objective evidence to support any chemoprotective agent for platinum-induced neurotoxicity.
Limits
Only a minority of trials evaluated the primary objective outcome of quantitative sensory testing, often with very small cohorts (e.g., 14 completing participants in the single amifostine QST trial). Methodological heterogeneity precluded meta-analysis for most objective endpoints, and risk of bias could frequently not be determined due to underreporting.
Cited by
- partial Co-administration of intravenous glutathione with platinum-based chemotherapies significantly reduces the incidence of peripheral neuropathy.