The Oncologist: commentary + link to original paper - Calcium and Magnesium Prophylaxis for Oxaliplatin-Related (taxanes) Neurotoxicity: Is It a Trade-off Between Drug Efficacy and Toxicity?

 1)  link to commentary: 

 Calcium and Magnesium Prophylaxis for Oxaliplatin-Related Neurotoxicity: Is It a Trade-off Between Drug Efficacy and Toxicity?

"In this context, a large international academic trial involving several U.S. and European oncological centers—the Chemotherapy-Induced Peripheral Neuropathy Outcome Measures Standardization (CI-PERINOMS) study[16]—recently completed the enrollment of >280 patients with CIPN who were examined with an extended series of scales and questionnaires to assess their reliability and validity, a critical step in the search for the optimal method to detect and describe its features in daily practice and in clinical trials. In fact, until reliable, valid, reproducible, and responsive methods are used to properly assess CIPN, any effort to establish an effective neuroprotection treatment will be unrealistic."

2)  link to original paper:

Calcium and Magnesium Prophylaxis for Oxaliplatin-Related Neurotoxicity: Is It a Trade-off Between Drug Efficacy and Toxicity?

"......Furthermore, there is a lack of standardization in timing of assessment of neurotoxicity and inadequate assessment of long-term neurotoxicity related to oxaliplatin between studies investigating Ca/Mg prophylaxis. Also, because of the initial concerns raised by the IDMC examining the CONCePT trial, many of the major trials were terminated early and are thus underpowered. The NCCTG has initiated another prospective randomized, double-blinded trial aimed at addressing these issues."  (safety)

abstract: Pyridoxine (Vitamin B6) to protect from oxaliplatin-induced neurotoxicity without compromising antitumour effect

CONCLUSIONS:

Administration of pyridoxine (Vitamin B6) , at concentrations extending across possible therapeutic plasma levels in humans, does not antagonise OHP (Oxaliplatin) antitumour effects in a range of relevant tumour cell lines.

This study provides a foundation for clinical studies to test whether pyridoxine can minimise OHP-related neurotoxicity, and clinicians can be confident that pyridoxine is very unlikely to reverse the antitumour effects of OHP, as seems to be the case with Ca/Mg infusions.

This could prove to be a cost-effective way to minimise OHP-related neurotoxicity, allowing more effective less toxic treatment and better outcomes in patients.

EvidenceUpdates - Interventions for preventing neuropathy caused by cisplatin and related compounds

BACKGROUND:
Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.


AUTHORS' CONCLUSIONS:
At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

Cochrane review: Interventions for preventing neuropathy caused by cisplatin and related compounds

AUTHORS' CONCLUSIONS: At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.