Po101 Management of Peripheral Neuropathy Induced by Nab-PTX Therapy for Breast Cancer

Ohno, Tsuyoshi; Inoue, Keiji; Haraguchi, Masashi; Mizutani, Takashi; Yoshioka, Hiroki; Matsuda, Kazuyuki; Kosaka, Mikiko; Morita, Michi; Kerckhove, Maiko de; Kitajima, Masachika; Ito, Shinichiro; Tokai, Hirotaka; Tanaka, Takayuki

doi:10.1016/s0960-9776(13)70114-0

Cited by 10 publications

(11 citation statements)

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“…Although limb hypothermia has commonly been used to ease pain and swelling due to sprain or surgery, no study has so far probed the minimal tolerated temperature for continuous cooling [15][16][17]. Our study has demonstrated for the first time that 22 C is the lowest temperature uniformly well tolerated for three hours in healthy subjects.…”

Section: Temperature Tolerability Threshold For Continuous Flow Limb mentioning

confidence: 75%

Hypothermia for preventing chemotherapy-induced neuropathy – a pilot study on safety and tolerability in healthy controls

et al. 2015

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Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of several chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and no effective treatment has been established so far. The mechanisms of CIPN damage are unclear, but are directly dose-related. We had earlier demonstrated, in rats, the influence of hypothermia in reducing nerve blood flow. Here, we hypothesize that continuous flow 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. Material and methods: In 15 healthy human subjects, hypothermia was administered as continuous flow cooling, unilaterally, via a thermoregulator setup covering the digits up to the elbow/knee, along with continuous skin temperature monitoring. Thermoregulator coolant temperatures between 25C and 20 C were tested for tolerability, based on a carefully designed temperature regulation protocol, and maintained for three hours mimicking the duration of chemotherapy. Tolerability was evaluated using various safety and tolerability scores to monitor the subjects. Results: At the end of the cooling session the healthy subjects presented without significant adverse effects, the main being brief mild skin erythema and transient numbness. Coolant temperatures as low as 22 C were well tolerated continuously over three hours. Conclusion: Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use 22 C thermoregulator temperature to investigate hypothermia in preventing CIPN in breast cancer patients receiving adjuvant weekly paclitaxel. This pilot study may contribute to alleviating chemotherapy dose limitation due to CIPN and increase the likelihood of success of chemotherapy.

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Section: Temperature Tolerability Threshold For Continuous Flow Limb mentioning

confidence: 75%

Hypothermia for preventing chemotherapy-induced neuropathy – a pilot study on safety and tolerability in healthy controls

et al. 2015

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“…As a result of clinical evidence that GJG has utility as a neuroprotectant when combined with various neurotoxic chemotherapeutics [Kaku, et al 2012, Abe, et al 2013, Ohno, et al 2014, Nishioka, et al 2011, Hosokawa, et al 2012, Yoshida, et al 2013], we treated cortical neurons with paclitaxel or oxaliplatin in the presence or absence of GJG for 72 hours and evaluated neurite changes in total outgrowth and cell viability. When cortical neurons were treated with paclitaxel plus 100 µg/mL GJG for 72 hours, there was a slight but significant decrease in paclitaxel-induced neurotoxicity as measured by relative total outgrowth, mean number of processes, mean/max process length, relative number of branches, cell numbers and cell viability and representative images (Figure 5 a–c).…”

Section: Resultsmentioning

confidence: 99%

“…With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine, a selective serotonin and norepinephrine reuptake inhibitor [Smith, et al 2013]. Goshajinkigan (GJG), a traditional Japanese herbal medicine, has been shown to inhibit the progression of neuropathy or alleviate symptoms of nerve pain resulting from chemotherapy treatment with paclitaxel/carboplatin for ovarian and endometrial cancer patients [Kaku, et al 2012], docetaxel in breast cancer patients [Abe, et al 2013], nab-paclitaxel for breast cancer patients [Ohno, et al 2014] and oxaliplatin in colorectal cancer patients [Nishioka, et al 2011, Hosokawa, et al 2012, Yoshida, et al 2013]. In animal models, GJG has been shown to suppress various transient receptor potential channels that may mitigate the pain responses in the patient [Mizuno, et al 2014, Kato, et al 2014, Matsumura, et al 2014].…”

Section: Introductionmentioning

confidence: 99%

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

et al. 2017

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The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy. We demonstrate differential sensitivity of neurons to mechanistically distinct classes of chemotherapeutics. We also show a dose-dependent reduction of electrical activity as measured by mean firing rate of the neurons following treatment with paclitaxel. We compared neurite outgrowth and cell viability of iPSC-derived cortical (iCell® Neurons) and peripheral (Peri.4U) neurons to cisplatin, paclitaxel and vincristine. Goshajinkigan, a Japanese herbal neuroprotectant medicine, was protective against paclitaxel-induced neurotoxicity but not oxaliplatin as measured by morphological phenotypes. Thus, we have demonstrated the utility of human iPSC-derived neurons as a useful model to distinguish drug class differences and for studies of a potential neuroprotectant for the prevention of chemotherapy-induced peripheral neuropathy.

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“…In this study, grade 2-3 peripheral sensory neuropathy led to dose reductions in 7 (19%) patients and delays in 10 (27%) patients. Ohno et al have reported that both compression therapy using stockings and sleeves, and medication therapy using selected prophylactic drugs (such as goshajinkigan or mecobalamin) improve the grade of peripheral neuropathy by controlling microcirculation for breast cancer patients treated with nab-PTX (15). Referring to this study, we also applied this therapy for unresectable or recurrent GC patients treated with nab-PTX and some patients appeared to improve their grade of peripheral neuropathy.…”

Section: Discussionmentioning

confidence: 61%

Efficacy of Nab-Paclitaxel as Second-line Chemotherapy for Unresectable or Recurrent Gastric Cancer

Fukuchi

Mochiki

Ishiguro

et al. 2016

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Po101 Management of Peripheral Neuropathy Induced by Nab-PTX Therapy for Breast Cancer

Cited by 10 publications

References 0 publications

Hypothermia for preventing chemotherapy-induced neuropathy – a pilot study on safety and tolerability in healthy controls

Hypothermia for preventing chemotherapy-induced neuropathy – a pilot study on safety and tolerability in healthy controls

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

Efficacy of Nab-Paclitaxel as Second-line Chemotherapy for Unresectable or Recurrent Gastric Cancer

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