Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study

Oki, Eiji; Emi, Yasunori; Kojima, Hiroshi; Higashijima, Jun; Kato, Takeshi; Miyake, Yasuhiro; Kon, Masanori; Osuga, Yutaka; Takahashi, Ken­ichi; Ishida, Hideyuki; Saeki, Hiroshi; Sakaguchi, Yoshihisa; Yamanaka, T.; Kono, Toru; Tomita, Naohiro; Baba, Hideo; Shirabe, Ken; Kakeji, Yoshihiro; Maehara, Yoshihiko

doi:10.1007/s10147-015-0784-9

Cited by 82 publications

(96 citation statements)

References 29 publications

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“…A549, SKOV3) to paclitaxel. However, we did not observe neuroprotection of oxaliplatin with GJG consistent with lack of clinical evidence from a randomized phase III study of GJG combined with oxaliplatin [Oki, et al 2015]. …”

Section: Discussionsupporting

confidence: 76%

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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Section: Discussionsupporting

confidence: 76%

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

et al. 2017

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“…About the safety of GJG, a recent phase 2, randomized, double-blind, placebo-controlled study concluded that GJG offers an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater oxaliplatin-induced peripheral neurotoxicity without impairing chemotherapy efficacy [48], confirming previous animal models findings [56]. To date, there are no strong recommendations about the use of specific neuroprotective agents and also the effectiveness of herbal medicines, such as GJG must be better elucidated [57][58][59]. Nevertheless, standard approaches, including amifostine and antidepressants have had limited efficacy and may themselves induce adverse side-effects, while herbal medicines has shown a better efficacy and safety profile.…”

mentioning

confidence: 65%

Pharmacological Approaches and Natural Products for Prevention of Chemotherapy-Induced Peripheral Neuropathy - A Review

Cascella

Muzio

2017

IJPPE

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Abstract. Chemotherapy-induced peripheral neuropathy (CIPN) is a one of the most common and severe cancer treatment-related adverse effect. It can often cause the stop of the treatment and affects the long-term quality of life of cancer survivors. Unfortunately, there are no effective agent or protocol to prevent with strong evidence of effectiveness this toxicity prevention of CIPN. Thus, CIPN prevention mainly consists of cumulative dose-reduction or lower dose-intensities, especially in higher risk patients. After a brief description of pathophysiology and features of CIPN, the purpose of this study is to analyse the role of standard pharmacological approaches and natural products for prevention of this serious side effect.

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“…The majority of the articles reviewed reported results of randomized trials ( N = 11) [19–21, 23, 24, 26–28, 31–33]. Other research designs included nonrandomized trials ( N = 5) [22, 34–37], cross-sectional studies ( N = 2) [3, 11], cohort studies ( N = 2) [25, 29], case series ( N = 1) [38], and a crossover trial ( N = 1) [30].…”

Section: Resultsmentioning

confidence: 99%

Lifestyle‐Related Factors in the Self‐Management of Chemotherapy‐Induced Peripheral Neuropathy in Colorectal Cancer: A Systematic Review

Derksen

Bours

Mols

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy treatment in colorectal cancer (CRC), negatively affecting the daily functioning and quality of life of CRC patients. Currently, there are no established treatments to prevent or reduce CIPN. The purpose of this systematic review was to identify lifestyle-related factors that can aid in preventing or reducing CIPN, as such factors may promote self-management options for CRC patients suffering from CIPN. Methods. A literature search was conducted through PubMed, Embase, and Google Scholar. Original research articles investigating oxaliplatin-related CIPN in CRC were eligible for inclusion. Results. In total, 22 articles were included, which suggested that dietary supplements, such as antioxidants and herbal extracts, as well as physical exercise and complementary therapies, such as acupuncture, may have beneficial effects on preventing or reducing CIPN symptoms. However, many of the reviewed articles presented various limitations, including small sample sizes and heterogeneity in study design and measurements of CIPN. Conclusions. No strong conclusions can be drawn regarding the role of lifestyle-related factors in the management of CIPN in CRC patients. Certain dietary supplements and physical exercise may be beneficial for the management of CIPN, but further research is warranted.

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Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study

Abstract: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.

Cited by 82 publications

References 29 publications

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

Pharmacological Approaches and Natural Products for Prevention of Chemotherapy-Induced Peripheral Neuropathy - A Review

Lifestyle‐Related Factors in the Self‐Management of Chemotherapy‐Induced Peripheral Neuropathy in Colorectal Cancer: A Systematic Review

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