- Title
- Pyridoxine to protect from oxaliplatin-induced neurotoxicity without compromising antitumour effect
- Creator
- Garg, Madhu B.; Ackland, Stephen P.
- Relation
- Cancer Chemotherapy and Pharmacology Vol. 67, Issue 4, p. 963-966
- Publisher Link
- http://dx.doi.org/10.1007/s00280-010-1476-9
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2011
- Description
- Purpose: Oxaliplatin (OHP) in combination with 5-Xuorouracil/leucovorin (FOLFOX) is clinically used as frontline therapy in patients with advanced colorectal carcinoma (CRC), with response rates ranging from 46 to 71%. This combination is now considered a standard treatment for metastatic CRC and also in the post-operative adjuvant setting. Reversible, cumulative, peripheral sensory neuropathy is the principal dose-limiting toxicity of OHP therapy. Pyridoxine (vitamin B6) has been shown to reduce cisplatin and Xuoropyrimidine-related neurotoxicity but its administration with OHP has not yet been studied. Low doses of pyridoxine are free of side effects; it can be given orally. If pyridoxine administration with oxaliplatin has no adverse effect on OHP cytotoxicity effects, it will be a simple and cost-effective way to minimise OHP-induced neurotoxicity. Methods: In vitro simultaneous combination of OHP and pyridoxine was studied in 6 CRC cell lines (HT29, Widr, SW480, HCT116, H630 and SW1116), in an ovarian cancer cell line (A2780) and its cisplatin-resistant subline (ADDP) and in an oestrogen-dependent breast cancer cell line (MCF-7). Three fixed concentrations of pyridoxine: 1, 10 and 25 μM were combined with varying concentrations of OHP, and the growth inhibitory effects were evaluated using the MTT cell growth assay. Results: Oxaliplatin induced consistent cytotoxicity in all cell lines with GI50 values between 0.23 and 7.6 μM. Addition of pyridoxine at concentrations of 1–25 μM does not affect OHP cytotoxicity. Conclusions: Administration of pyridoxine, at concentrations extending across possible therapeutic plasma levels in humans, does not antagonise OHP 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.
- Subject
- oxaliplatin; pyridoxine; neurotoxicity; colorectal cancer; cell lines; MTT
- Identifier
- http://hdl.handle.net/1959.13/936419
- Identifier
- uon:12304
- Identifier
- ISSN:0344-5704
- Language
- eng
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