TO THE EDITOR: We read with special attention the letter from Hochster, Grothey, and Childs about preliminary results of the Combined Oxaliplatin Neuropathy Prevention Trial. 1 Theaimsofthisstudyweretoexploretwoapproachesinfirst-line chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) bevacizumab for metastatic colorectal cancer—the Stop-and-Go strategy from the French Oncology Research Group (GERCOR) group developed in the Stop-and-Go strategy study and the prevention of neurotoxicity with calcium and magnesium (Ca2-Mg2) infusion. According to these authors, preliminary results have led to suspect a lesser response rate in the two arms of patients treated with FOLFOX-bevacizumab plus Ca2-Mg2, and the authors decided to stop the administration of Ca2 Mg2. We would like to step back to the concept of Ca2-Mg2 infusions for preventing oxaliplatin-induced neurotoxicity. Obviously, oxaliplatin-induced neurotoxicity is the drug-limiting toxic adverse effect. It alters patients’ quality of life and can lead to postponed or even interrupted treatments with oxaliplatin. Considering the unique profile of acute oxaliplpatin-induced neurotoxicity, we suspected that certain ionic channels could be involved as it has been described in channellopathies, or Na channels inhibitors poisoning, such as tetrodotoxin. We showed in electrophysiological studies with patch-clamp technique that oxaliplatin, and more precisely one of its two direct metabolites, the oxalate, which is a potent Ca2 chelator, interferes with certain ionic channels expressed on the peripheral neurones (Ca2 dependent voltage-gated Na channels). 3 On the other hand, diamminocyclohexane platin, the active cytotoxic metabolite, had no effect on the Na channels. The hypothesis was that when oxaliplatin enters the neurones, it splits into diamminocyclohexane platin and oxalate, and the latter one chelates Ca and interferes with Na channel activity, leading to a neurone ehyperexcitability, and secondarily, to a chronic neuropathy. We tested Ca2 and Mg2 infusion as chelators of oxalate to inhibit its action on Na channels and could show in a retrospective study a dramatic decrease of acute and chronic neurotoxicity, with no impact on oxaliplatin efficacy. In the French multicentric “Neuroxa” study, patients were randomly assigned in a double blind randomized study designed to prove the interest of Ca2 and Mg2 infusions for preventing oxaliplatin neurotoxicity. 2 One hundred forty-four patients have been treated with the FOLFOX 4 regimen, with 85 mg/m2 oxaliplatin every 2 weeks. They either received or did not receive calcium gluconate 1g and magnesium sulfate 1.5 g, administered in 250-mL glucose serum just before and just after oxaliplatin infusion. In the first 52 patients treated for metastatic colorectal cancer in first-line therapy, we reviewed the data in term of patients’ characteristics, efficacy, and neurotoxicity. These 52 patients are split into two groups, with and without Ca2 and Mg2 infusion, respectively. Since all the data are not collected and treated yet, we did not take off the blind. These preliminary results were presented at the 2007 International Society of Gastrointestinal Oncology meeting in Philadelphia, PA, and will be published in its newsletter. The two groups are well balanced in term of age, Eastern Cooperative Oncology Group (ECOG) performance status, primary tumor, number of metastases, and number of metastatic sites. There is neither difference in term of objective response rate (50% v 53%, P. 45), nor in progression-free (12 0.6 SE v 12 0.5 SE, P. 79) and overall survivals (25.1 4 SE v 25.5 4.1 SE, P. 45). On the other hand, we report a …