Single-arm, open-label, dose-escalation phase I study to evaluate the safety of a herbal medicine SH003 in patients with solid cancer: a study protocol

Cheon, Chunhoo; Kang, Sohyeon; Ko, Youme; Kim, Mia; Jang, Bo‐Hyoung; Shin, Yong‐Cheol; Ko, Seong‐Gyu

doi:10.1136/bmjopen-2017-019502

Cited by 8 publications

(10 citation statements)

References 23 publications

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“…SH003 is a herbal formula comprising three medicinal herbs, Astragalus membranaceus (Am), Angelica gigas (Ag), and Tk. Accumulating evidence has demonstrated that SH003 has anti-cancer efficacy against various types of cancer [35,36,45], and clinical trials have been conducted to analyze the efficacy and safety of SH003 in patients with solid cancers [32,53]. The effect of SH003 in chemotherapy-induced neuropathic pain has been demonstrated in docetaxel-induced mechanical allodynia [54]; however, its effect on paclitaxel has never been investigated.…”

Section: Discussionmentioning

confidence: 99%

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Analgesic Effect of SH003 and Trichosanthes kirilowii Maximowicz in Paclitaxel-Induced Neuropathic Pain in Mice

Lee

Kim

et al. 2022

CIMB

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Pacliatxel is a taxol-based chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are prescribed to attenuate neuropathies, no optimal treatment is available. Thus, in our study, we analyzed whether SH003 and its sub-components could alleviate paclitaxel-induced neuropathic pain. Multiple paclitaxel injections (cumulative dose 8 mg/kg, i.p.) induced cold and mechanical allodynia from day 10 to day 21 after the first injection in mice. Oral administration of SH003, an herbal mixture extract of Astragalus membranaceus, Angelica gigas, and Trichosantheskirilowii Maximowicz (Tk), dose-dependently attenuated both allodynia. However, when administered separately only Tk decreased both allodynia. The effect of Tk was shown to be mediated by the spinal noradrenergic system as intrathecal pretreatment with α1- and α2-adrenergic-receptor antagonists (prazosin and idazoxan), but not 5-HT1/2, and 5-HT3-receptor antagonists (methysergide and MDL-72222) blocked the effect of Tk. The spinal noradrenaline levels were also upregulated. Among the phytochemicals of Tk, cucurbitacin D was shown to play a major role, as 0.025 mg/kg (i.p.) of cucurbitacin D alleviated allodynia similar to 500 mg/kg of SH003. These results suggest that Tk should be considered when treating paclitaxel-induced neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

“…SH003 is a complex formula composed of an ethanol extract of three medicinal herbs, namely Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz [32]. Previous studies have reported its anti-cancer effects on various types of cancer cells, such as breast, lung, and prostate cancer [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Analgesic Effect of SH003 and Trichosanthes kirilowii Maximowicz in Paclitaxel-Induced Neuropathic Pain in Mice

Lee

Kim

et al. 2022

CIMB

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“…The study protocol was previously published before study completion. We followed the methods described by Cheon et al 17…”

Section: Study Design and Ethical Approvalmentioning

confidence: 99%

A Phase I Study to Evaluate the Safety of the Herbal Medicine SH003 in Patients With Solid Cancer

Cheon

2020

Integr Cancer Ther

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Background: Cancer is a major health problem worldwide and the leading cause of death in many countries. Preclinical studies have shown the therapeutic anticancer effects of SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. The present study investigated the maximum tolerated dose of SH003 in patients with solid cancers. Methods: This open-label, dose-escalation trial used the traditional 3 + 3 dose-escalation design. Patients with solid cancers were recruited and administered 1 to 4 tablets of SH003 thrice daily for 3 weeks according to the dose level. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Dose-limiting toxicities (DLTs) were defined as Grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. Results: The present study enrolled 11 patients. A total of 31 adverse events occurred. According to the CTCAE, all the observed adverse events were grade 2 or less and no adverse events of grade 3 or more corresponding to DLT occurred. Conclusion: The study results indicated that the maximum tolerated dose of SH003 was 4800 mg/day. A Phase 2 study is required to determine the efficacy of SH003 in patients with cancer at a dose of 4800 mg/day or less.

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“…e anticancer effect of SH003 against breast, lung, and prostate cancer has been demonstrated through several in vitro and in vivo studies [30][31][32][33][34][35][36][37][38]. e safety of SH003 was proved by phase I clinical study for solid tumors, and phase II clinical study for wildtype EGFR lung cancer patients is in progress [39][40][41]. Meanwhile, phase I/II clinical study of SH003 combined with docetaxel for breast and lung cancer patients is also in progress (NCT01755923, https://clinicaltrials.gov).…”

Section: Introductionmentioning

confidence: 99%

Herbal Prescription SH003 Alleviates Docetaxel-Induced Neuropathic Pain in C57BL/6 Mice

Lee

Choi

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Docetaxel-based therapy has been applied to kill cancers including lung and breast cancers but frequently causes peripheral neuropathy such as mechanical allodynia. Lack of effective drugs for chemotherapy-induced peripheral neuropathy (CIPN) treatment leads us to find novel drugs. Here, we investigated whether and how novel anticancer herbal prescription SH003 alleviates mechanical allodynia in mouse model of docetaxel-induced neuropathic pain. Docetaxel-induced mechanical allodynia was evaluated using von Frey filaments. Nerve damage and degeneration in paw skin of mice were investigated by immunofluorescence staining. Neuroinflammation markers in bloodstream, lumbar (L4-L6) spinal cord, and sciatic nerves were examined by ELISA or western blot analysis. Docetaxel (15.277 mg/kg) was intravenously injected into the tail vein of C57BL/6 mice, and mechanical allodynia was followed up. SH003 (557.569 mg/kg) was orally administered at least 60 min before the mechanical allodynia test, and von Frey test was performed twice. Docetaxel injection induced mechanical allodynia, and SH003 administration restored withdrawal threshold. Meanwhile, degeneration of intraepidermal nerve fibers (IENF) was observed in docetaxel-treated mice, but SH003 treatment suppressed it. Moreover, docetaxel injection increased levels of TNF-α and IL-6 in plasma and expressions of phospho-NF-κB and phospho-STAT3 in both of lumbar spinal cord and sciatic nerves, while SH003 treatment inhibited those changes. Taken together, it is worth noting that TNF-α and IL-6 in plasma and phospho-NF-κB and phospho-STAT3 in spinal cord and sciatic nerves are putative biomarkers of docetaxel-induced peripheral neuropathy (DIPN) in mouse models. In addition, we suggest that SH003 would be beneficial for alleviation of docetaxel-induced neuropathic pain.

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Single-arm, open-label, dose-escalation phase I study to evaluate the safety of a herbal medicine SH003 in patients with solid cancer: a study protocol

Cited by 8 publications

References 23 publications

Analgesic Effect of SH003 and Trichosanthes kirilowii Maximowicz in Paclitaxel-Induced Neuropathic Pain in Mice

Analgesic Effect of SH003 and Trichosanthes kirilowii Maximowicz in Paclitaxel-Induced Neuropathic Pain in Mice

A Phase I Study to Evaluate the Safety of the Herbal Medicine SH003 in Patients With Solid Cancer

Herbal Prescription SH003 Alleviates Docetaxel-Induced Neuropathic Pain in C57BL/6 Mice

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