goshajinkigan (TJ-107) / Tsumura - LARVOL DELTA

REAL-WORLD UTILIZATION OF TRADITIONAL JAPANESE KAMPO MEDICINE AS SUPPORTIVE CARE IN PATIENTS UNDERGOING CHEMOTHERAPY (IGCS 2025) - "Twenty-eight Kampo formulations were used, with the most common being Goshajinkigan (91 cases, 47.6%), Daikenchuto (82, 42.9%), and Shakuyakukanzoto (15, 7.9%). Regarding chemotherapy regimens, 123 patients (63.4%) received TEC (paclitaxel, epirubicin, carboplatin), and 53 (27.7%) received TC... Among endometrial cancer patients who underwent chemotherapy during the study period, 339 cases were identified. Of these, 191 (56.3%) received Kampo prescriptions. The median age was 60 years (range, 28–85)."

Clinical • Real-world • Real-world evidence • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Co-treatment with Gabapentinoid and Japanese Herbal Medicine Goshajinkigan for CIPN is Associated with Longer Duration and Higher Dose of Chemotherapy. (PubMed, Adv Ther) - "Combination treatment with gabapentinoid plus GJG might prevent reductions in dose or discontinuation of chemotherapy, and might be effective for the treatment of CIPN."

Journal • Breast Cancer • Colorectal Cancer • Gastric Cancer • Oncology • Pain • Solid Tumor

Preventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced neuropathic pain. (PubMed, J Nat Med) - "Currently, there are no effective prophylactic or therapeutic drugs for the treatment of paclitaxel (PTX)-induced peripheral neuropathic pain (PTX-PNP), highlighting the urgent need for the development of effective prophylactic and therapeutic drugs. In contrast, goshajinkigan, a Kampo medicine, and diclofenac, a non-steroidal anti-inflammatory drug, showed minimal therapeutic effects on PTX-PNP. These findings demonstrate the significant potential of EFE as a novel, safe prophylactic and therapeutic agent against PTX-PNP."

Journal • Neuralgia • Oncology • Pain • Peripheral Neuropathic Pain

Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice. (PubMed, Fitoterapia) - "The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging...officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea...The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation."

Journal • Preclinical • Constipation • Diabetes • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Osteoporosis • Peptic Ulcer • Rheumatology

Effectiveness of the Traditional Japanese Medicine Goshajinkigan in Preventing Paclitaxel-Induced Peripheral Neuropathy: A Multicenter Randomized Comparative Trial. (PubMed, Integr Cancer Ther) - " This study enrolled 55 patients with ovarian cancer undergoing first-line chemotherapy using paclitaxel and carboplatin. GJG, when administered prophylactically, showed potential for mitigating CIPN symptoms during paclitaxel chemotherapy. While promising, further research with placebo controls and objective measures is essential to comprehensively validate these findings."

Clinical • Journal • Oncology • Ovarian Cancer • Pain • Solid Tumor

A randomized, open-label phase II study on the preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: The OLCSG2101 study protocol. (PubMed, Respir Investig) - "The results of this study may contribute to better management of CIPN, which can enable the continuation of chemotherapy and maintenance of the patient's QOL."

Clinical • Clinical protocol • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Thymus Cancer

Study of perioperative dose-dense chemotherapy at our hospital (JBCS 2024) - "The taxanes used were dose dense paclitaxel (ddPTX) in 19 patients, weekly paclitaxel (wPTX) in 31 patients, and nab-paclitaxel (nab-PTX) in 3 patients...Peripheral neuropathy is a frequent side effect of taxanes, but only two cases required dose reduction, and the rest were able to be controlled with goshajinkigan, pregabalin, and mirogabalin besilate...Conclusion Dose-dense chemotherapy showed a high completion rate and was relatively safe. Furthermore, dose-dense chemotherapy showed a high pCR rate in preoperative chemotherapy for HER2-negative breast cancer, and is considered to be an effective treatment"

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Solid Tumor • Triple Negative Breast Cancer • HER-2

CANCER SUPPORT CLINIC USING KAMPO MEDICINE (MASCC-AFSOS-ISOO 2024) - "Goshajinkigan (TJ-107) was used for paclitaxel-induced PN, and ninjin'yoeito (TJ-108) was used for oxaliplatin-induced PN. Other symptoms (and Kampo prescription) included niraparib-induced nausea & vomiting in a patient with recurrent ovarian cancer (heiisan, TJ-79), multiple pain (not due to metastasis) in a postoperative patient with breast cancer (goshakusan, TJ-63), and oral mucositis in a patient with recurrent non-small cell lung cancer (hangeshashinto, TJ-14). In some patients, a single Kampo prescription effectively ameliorated multiple symptoms, indicating a potential polypharmacy solution. Conclusions Kampo medicines, high-quality pharmaceutical products, have been well applied in cancer support clinic in Japan."

Anorexia • Breast Cancer • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pain • Peripheral Neuropathic Pain • Sarcopenia • Solid Tumor • Stomatitis

The Role Of Diet And Non-pharmacologic Supplements In The Treatment Of Chronic Neuropathic Pain: A Systematic Review (ASA 2023) - "The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-L-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), L-carnosine (1), magnesium and calcium (1), crocin (1) and antioxidants (1), with some studies involving multiple interventions... Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, L-carnosine, crocin and magnesium is warranted. Acetyl-L-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective."

Review • Diabetic Neuropathy • Musculoskeletal Pain • Neuralgia • Oncology • Pain • Peripheral Neuropathic Pain

Efficacy and safety of drug therapy for the prevention and treatment of chemotherapy-induced peripheral neuropathy: a protocol for a systematic review and network meta-analysis. (PubMed, BMJ Open) - "We will include studies that investigated the efficacy and safety of vitamin B, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN...The research will be published in a peer-reviewed journal. CRD42022371829."

Journal • Retrospective data • Review • Oncology • Pain

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review. (PubMed, Pain Pract) - "Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings."

Journal • Review • Diabetic Neuropathy • Musculoskeletal Pain • Neuralgia • Oncology • Pain • Peripheral Neuropathic Pain

Efficacy and safety of dose-dense neoadjuvant chemotherapy with nab-paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer. (PubMed, Jpn J Clin Oncol) - "Neoadjuvant dose-dense biweekly nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide was effective, especially in patients with triple-negative disease, and feasible with pegfilgrastim support."

Journal • Breast Cancer • Fatigue • Febrile Neutropenia • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Solid Tumor • Triple Negative Breast Cancer • HER-2

Preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: An open-label, randomized, phase II study. (ASCO 2022) - " Patients have to meet the followings: pathologically diagnosed with malignant tumor (regardless of cancer type) and scheduled to receive ≥4 courses of chemotherapy including carboplatin and paclitaxel (paclitaxel ≥150mg/m2 every 3-4 weeks) as initial chemotherapy; age ≥20yrs; Performance Status of 0 or 1. The secondary endpoint includes time to the onset of CIPN G2, incidence rate and severity of CIPN at the end of each course, relative dose intensity of paclitaxel, adverse events other than CIPN. Enrollment began in 2022, and will be complete by 2025."

Clinical • P2 data • Diabetic Neuropathy • Oncology • Pain • Peripheral Neuropathic Pain • Solid Tumor

Behavioral and Immunohistochemical Evidence for Suppressive Effects of Goshajinkigan on Salicylate-Induced Tinnitus in Rats. (PubMed, Brain Sci) - "The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models."

Journal • Preclinical • Otorhinolaryngology • Palliative care • FOS

NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: Hyunseok Kang, MD; Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Dietary Supplements in Chemotherapy-Induced Peripheral Neuropathy: A New Hope? (PubMed, Nutrients) - "As proposed, acetyl-L-carnitine, vitamins (group B and E), extracts of medical plants, including goshajinkigan, curcumin and others, unsaturated fatty acids, as well as the diet composed of so-called "sirtuin-activating foods", could change the typical way of treatment of CIPN, improve the quality of life of patients and maintain the continuity of chemotherapy. This review summarizes currently available data regarding mentioned above agents and evaluates the rationale behind future research focused on their efficacy in CIPN."

Journal • Review • Oncology • Pain

Kampo medicines for supportive care of patients with cancer: A brief review. (PubMed, Integr Med Res) - "Potential use of rikkunshito for anorexia/cancer cachexia and goshajinkigan for peripheral neuropathy is proposed from small numbers of randomized controlled trials in addition to basic research...Kampo medicines potentially play some roles in preventing or ameliorating side effects of anticancer agents. Supportive care with Kampo medicines for patients with cancer might lead to physical, mental, and nutritional improvement."

Journal • Review • Anorexia • Cachexia • Fatigue • Oncology • Pain

Risk factors for interstitial lung disease induced by gemcitabine plus albumin-bound paclitaxel therapy in pancreatic ductal adenocarcinoma patients. (PubMed, J Pharm Health Care Sci) - "These results suggest that administration of goshajinkigan to patients receiving GnP therapy for prevention of CIPN may need to be reconsidered."

Journal • Gastrointestinal Disorder • Hepatology • Interstitial Lung Disease • Oncology • Pain • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Pancreatitis • Pulmonary Disease • Respiratory Diseases

Gosha-jinki-Gan (GJG) shows anti-aging effects through suppression of TNF-α production by Chikusetsusaponin V. (PubMed, Gene) - "In 8-week-old SAMP8 mice fed 4% (w/w) GJG from one week to four weeks, the plasma CsV concentration ranged from 0.0500 to 10.0 ng/mL. The evidence that CsV plays an important role in various anti-aging effects of GJG via suppression of TNF-⍺ expression is presented."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Muscular Atrophy • Oncology • Pain • Sarcopenia • FBXO32 • FBXW7 • RELA • TNFA

Risk factors and pharmacotherapy for chemotherapy-induced peripheral neuropathy in paclitaxel-treated female cancer survivors: A retrospective study in Japan. (PubMed, PLoS One) - "Drugs prescribed for PIPN included duloxetine, pregabalin, mecobalamin and Goshajinkigan, a polyherbal medicine, regardless of poor evidence for their effectiveness against CIPN, and were greatly different between breast and gynecologic cancer patients diagnosed with PIPN at the departments of Surgery and Gynecology, respectively. Thus, older age, greater total paclitaxel dose, the history of estrogen-related diseases, hypertension and BMI are considered risk factors for PIPN in paclitaxel-based chemotherapy of female cancer patients. It appears an urgent need to establish a guideline of evidence-based pharmacotherapy for PIPN."

Journal • Retrospective data • Gynecologic Cancers • Gynecology • Hypertension • Oncology • Pain • Peripheral Neuropathic Pain

Effects of Goshajinkigan (TJ-107) for oxaliplatin-induced peripheral neurotoxicity using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire in a Phase II, multicenter, randomized, double-blind, placebo-controlled trial. (PubMed, J Cancer Res Ther) - "The comparisons of the median scores for TJ-107 and the placebo at 8 and 26 weeks were as follows: numbness or tingling in the hands (P = 0.5820), numbness or tingling in the feet (P = 0.3236), feeling of discomfort in the hands (P = 0.8219), feeling of discomfort in the feet (P = 0.5361), joint pain or muscle cramps (P = 0.1974), feeling weak all over (P = 0.2771), trouble hearing (P = 0.2832), ringing or buzzing in ears (P = 0.1031), trouble buttoning buttons (P = 0.1653), trouble feeling the shape of small objects when held in hand (P = 0.2919), trouble walking (P = 0.5406), and pain in the hands or feet when exposed to cold temperatures (P = 0.1872). There might be no clinically significant difference between the use of TJ-107 and the severity and quality of life for patients treated with oxaliplatin."

Clinical • Journal • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Pain • Solid Tumor

Compression therapy and goshajinkigan for prevention of nab-paclitaxel-induced peripheral neuropathy in patients with operable breast cancer (SABCS 2021) - "Nab-PTX (260mg/m2) followed by epirubicin (90mg/m2) plus cycrlophosphamide (600mg/m2) administered every 2 weeks with pegfilgrastim support. Compression therapy with elastic stockings and GJG were effective to prevent PN associated with DD nab-PTX regimen. Preventive approach for PN may improve dose intensity of taxane and long-term QOL of breast cancer patients."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Roles of Kampo Medicine in Modern Cancer Therapy: Towards Completion of Standard Treatment. (PubMed, J Nippon Med Sch) - "There is accumulating evidence for the following Kampo formula for each symptom: Hangeshashinto for mucositis, rikkunshito for anorexia, goshajinkigan and ninjin'yoeito for peripheral neuropathy, hochuekkito for general malaise/fatigue, and shakuyakukanzoto for myalgia/arthralgia. However, there is insufficient evidence, and further clinical trials are needed. Supportive care with Kampo Medicine will lead to a more complete standard treatment for cancer."

Journal • Anorexia • Fatigue • Mucositis • Musculoskeletal Pain • Oncology • Pain

Goshajinkigan attenuates paclitaxel-induced neuropathic pain via cortical astrocytes. (PubMed, Pharmacol Res Perspect) - "Finally, the inhibition of S1 astrocytes by an astrocyte-toxin L-alpha-aminoadipic acid abolished the PCX-induced neuropathy. Our findings suggest that astrocytes in the S1 cortex would play an important role in the pathogenesis of PCX-induced neuropathy and are a potential target for its treatment."

Journal • Review • Neuralgia • Oncology • Pain • Peripheral Neuropathic Pain

A Phase I/IIa, Open-label, Dose-Escalation and expansion study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TJ107 in Chinese Patients with Advanced Solid Tumors (SITC 2019) - P1/2; "Preliminary results from this trial suggest that TJ107 activated IL-7 pathway and expanded T cells in cancer patients in a similar way to data previously reported in healthy subjects. TJ107 exhibits a promising safety and tolerability profile in cancer patients under current dose. These findings support further clinical investigation."

Clinical • IO Biomarker • P1/2 data • PK/PD data