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Skin platinum deposition in colorectal cancer patients following oxaliplatin-based therapy

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

We thank Jing Xu for valuable technical assistance.

Funding

Funding for this study was provided by Princess Margaret Cancer Center Foundation.

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Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Room 7-824, 700 University Avenue, Toronto, ON, M5G 1X6, Canada

    Yanshuo Cao, Wenjiang Zhang, David Hedley & Eric X. Chen

  2. Faculty of Medicine, University of Toronto, Toronto, Canada

    Yanshuo Cao, David Hedley & Eric X. Chen

  3. Fluidigm Canada Inc., Markham, Canada

    Qing Chang & Olga Ornatsky

Authors
  1. Yanshuo Cao
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  2. Qing Chang
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  3. Wenjiang Zhang
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  4. Olga Ornatsky
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  5. David Hedley
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  6. Eric X. Chen
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Corresponding author

Correspondence to Eric X. Chen.

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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.

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Cao, Y., Chang, Q., Zhang, W. et al. Skin platinum deposition in colorectal cancer patients following oxaliplatin-based therapy. Cancer Chemother Pharmacol 84, 1195–1200 (2019). https://doi.org/10.1007/s00280-019-03956-6

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  • DOI: https://doi.org/10.1007/s00280-019-03956-6

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