Intraepidermal Nerve Fibre Density in Cancer Patients Receiving Adjuvant Chemotherapy

Background: Chemotherapy-induced neuropathy is a common adverse event in patients receiving vinca alcaloids, platinum derivatives and taxanes. However, the underlying pathogenetic mechanisms have not been completely elucidated. We set up a prospective pilot study on skin biopsies in newly diagnosed cancer patients receiving neurotoxic chemotherapeutic agents as adjuvant treatment in order to study the occurrence of small-fibre pathology and its relationship to clinical symptoms. Patients and Methods: Skin biopsies from distal leg were performed in 12 patients before, during and after chemotherapy. Using light microscopy, the intraepidermal nerve fibre (IENF) density was determined from the skin biopsies by counting morphometrically the immunopositive nerves per epidermal area. Results: Reduced IENF density was observed in eight patients at baseline. During the follow-up, the IENF density increased significantly in six patients and remained unchanged in two. In four patients, the IENF density was normal both at baseline and at the end of the follow-up period. Neuropathic symptoms were manifested in nine patients, but no association with the IENF count was found. Conclusion: During chemotherapy, results from patients revealed different evolutionary patterns of IENF density, but symptoms and IENF density were not related. Chemotherapy is one of the most effective therapies of cancer. It is used both as adjuvant therapy and as treatment for advanced cancer. Survival benefit of adjuvant chemotherapy has been demonstrated in breast, ovarian and colorectal cancer, and its role is under research for many other malignancies. In advanced cancer, chemotherapy prolongs survival and improves quality of life by preventing cancer-related symptoms. However, chemotherapy has many adverse effects: haematological and gastrointestinal toxicity, manifested as mucositis and diarrhoea, alopecia, nephrotoxicity, cardiotoxicity and neurotoxicity. Most of these toxicities are reversible, but some, such as neurotoxicity, can also be permanent. The long-term adverse effects of chemotherapy are becoming more important as more cancer patients are being cured. The most neurotoxic chemotherapeutic agents are platinum