Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect of several commonly used chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and it is noteworthy that no effective treatment has been established so far. In this study, we assess the effect of hypothermia in preventing CIPN in healthy subjects and then, cancer subjects undergoing adjuvant paclitaxel chemotherapy. This study may contribute to alleviating dose-limitation due to CIPN and increase the likelihood of success of chemotherapy.
1. Imaging of temperature dependent hemodynamics in the rat sciatic nerve by functional photoacoustic microscopy. L. D. Liao, J. Orellana, Y. H. Liu, Y. R. Lin, A. Vipin, N. V. Thakor, K. Shen, and E. Wilder-Smith, Biomedical engineering online, vol. 12, pp. 120-32, Nov 2013.
The mechanisms of the peripheral nerve damage induced by paclitaxel are unclear, but are directly dose related. We have demonstrated the influence of hypothermia in reducing nerve blood flow in rats. This study underlies the hypothesis that limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves.
Additionally, future work will be directed towards gaining in-depth knowledge of the neuroprotective mechanisms promoted by hypothermia. We will develop an animal model of paclitaxel-induced peripheral neuropathy and probe the blood perfusion and nerve conduction changes with hypothermia, using the multimodal imaging system and mass spectrometric analysis. Since CIPN is a major dose-limiting side-effect of chemotherapy, this proposed technique will indeed improve the lifestyle of cancer patients.
Hypothermia for Preventing Chemotherapy-Induced Neuropathy - A Pilot Study on Safety and Tolerability in Healthy Controls. A.Bandla, R.Sundar, L. D. Liao, S.Tan, S.Lee, N. V. Thakor, and E. Wilder-Smith, Acta oncologica 2015 submitted.
We hypothesize that limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves. In this study, prior to assessing the effect of hypothermia in preventing CIPN in cancer subjects undergoing paclitaxel chemotherapy, we assess the safety and tolerable temperatures for limb hypothermia in healthy human subjects. Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use achieved tolerable temperature to investigate hypothermia in preventing CIPN in breast-cancer patients receiving adjuvant weekly paclitaxel. This pilot study may contribute to alleviating dose-limitation due to CIPN and increase the likelihood of success of chemotherapy.