Hypothesis
Calmangafodipir, which reduced patient-reported chemotherapy-induced peripheral neuropathy in a randomised phase 2 trial, would prevent moderate-to-severe neuropathy in patients receiving oxaliplatin in the adjuvant and metastatic settings.
What failed
Both POLAR trials (n = 301 and 291) stopped early after unexpected hypersensitivity reactions. In the pooled primary analysis, 54.3% of calmangafodipir patients had moderate-to-severe neuropathy at month 9 versus 40.3% on placebo (relative risk 1.37, 95% CI 1.01–1.86, P = .045), and serious hypersensitivity reactions were more frequent (3.6% vs 0.8%).
Broken assumption
Targeting oxidative stress prevents oxaliplatin-induced peripheral neuropathy, as a phase 2 trial suggested.
Why
Not only was there no benefit, the drug arm did worse on the primary endpoint. The authors frame the result as showing the difficulty of preventing this neuropathy by targeting oxidative stress.
From the published paper: Pfeiffer et al. JNCI Cancer Spectrum, 2022. ↗CC BY