Research Papers:

The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients

Roxanne J. Wadia, Marilyn Stolar, Clarice Grens, Barbara E. Ehrlich and Herta H. Chao _

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Oncotarget. 2018; 9:7322-7331. https://doi.org/10.18632/oncotarget.23467

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Roxanne J. Wadia1,2,5, Marilyn Stolar3, Clarice Grens5, Barbara E. Ehrlich2,4 and Herta H. Chao1,2,5

1Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA

2Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA

3Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, USA

4Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut, USA

5VA Connecticut Healthcare System, West Haven, Connecticut, USA

Correspondence to:

Herta H Chao, email: [email protected]

Keywords: chemotherapy; taxane; vinca alkaloid; lithium; valproic acid

Received: September 12, 2017     Accepted: November 20, 2017     Published: December 19, 2017


Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment. We previously found that drugs that interfere with the microtubule function, including taxanes and vinca alkaloids, bind to neuronal calcium sensor 1 (NCS1), leading to aberrant calcium signaling. The altered calcium signaling can be mitigated by application of drugs used to treat bipolar disease (e.g., lithium and valproic acid) prior to initiation of chemotherapy. Because pre-treatment with these drugs prevented CIPN in mice treated with taxanes, we sought clinical evidence by performing a retrospective chart review study of the VA electronic health record to see whether or not there would be evidence to support our scientific belief that patients treated with lithium or valproic acid while receiving chemotherapy have a lower risk for development of CIPN than patients who received chemotherapy alone. Our data did provide evidence supporting the belief that treatment with lithium or valproic acid concurrently with chemotherapy was associated with a decreased incidence of developing CIPN.

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