Skin platinum deposition in colorectal cancer patients following oxaliplatin-based therapy
Oxaliplatin is widely used in the treatment of gastrointestinal malignancies. One of the most common and dose-limiting side effects of oxaliplatin is the chronic peripheral sensory neuropathy. The mechanism of this neurotoxicity is poorly understood and there are no effective preventive or treatment strategies, other than oxaliplatin dose interruption or reduction.
Colorectal cancer patients who completed FOLFOX at least 6 months prior to enrollment were eligible. EORTC QLQ-CIPN20 questionnaire was used for assessing self-reported neuropathic symptom. Blood samples and skin biopsies were obtained and analyzed for platinum.
Twelve patients were enrolled. The mean cumulative dose of oxaliplatin was 818 ± 54 mg/m2, and the median time from last dose of oxaliplatin was 38.7 months (range: 7.2–65.6 months). The QLQ-CIPN20 sensory score was 18 or less in 10 patients and 19 and 25, respectively, in 2 patients. Platinum was detectable in plasma from 4/12 patients up to 63.3 months after the completion of FOLFOX. In all six patients with skin biopsies, platinum was present in the skin with imaging mass cytometry.
QLQ-CIPN20 scores and plasma platinum concentrations were not related to cumulative doses of oxaliplatin or interval from the last dose of oxaliplatin. Platinum was readily detectable in skin biopsies more than 60 months post-completion of FOLFOX. This is the first demonstration of platinum deposition in skin post-oxaliplatin treatment and it provides a possible mechanism for oxaliplatin-induced peripheral sensory neuropathy and its persistence.
KeywordsColorectal cancer Platinum Peripheral sensory neuropathy Oxaliplatin Image mass cytometry
We thank Jing Xu for valuable technical assistance.
Funding for this study was provided by Princess Margaret Cancer Center Foundation.
Compliance with ethical standards
Conflict of interest
Qing Chang and Olga Ornatsky are employees of Fluidigm Canada Inc. Olga Ornatsky is one of the co-founders of DVS Sciences Inc. (now part of Fluidigm) that invented, developed and manufactures mass cytometry technologies, including the Helios CyTOF system, the Imaging Mass Cytometer and metal-conjugated reagents. No other authors declared any potential conflicts of interest.
- 19.Misery L, Bodere C, Genestet S et al (2014) Small-fibre neuropathies and skin: news and perspectives for dermatologists. Eur J Dermatol 24:147–153Google Scholar
- 25.Gamelin E, Bouil AL, Boisdron-Celle M et al (1997) Cumulative pharmacokinetic study of oxaliplatin, administered every three weeks, combined with 5-fluorouracil in colorectal cancer patients. Clin Cancer Res 3:891–899Google Scholar