Phase I study to evaluate the maximum tolerated dose of the combination of SH003 and docetaxel in patients with solid cancer

Abstract

Introduction: Cancer is the second leading cause of death, and the burden of cancer continues to grow globally. Research on the efficacy of combined administration of herbal medicine and anticancer drugs is also increasing. SH003 is a new herbal medicine composed of Astragalus membranaceus , Angelica gigas , and Trichosanthes kirilowii . SH003 alone up to 4800 mg daily was found to be safe. Preclinical studies have shown SH003 to have a synergistic effect with coadministration of anticancer drugs. This study aimed to determine the maximum tolerated dose of SH003 combined with docetaxel in patients with lung or breast cancer. Methods: This is an open-label, dose-escalation study to evaluate the safety of SH003 combined with docetaxel. Patients with lung or breast cancer will be recruited. The participants will be divided into 3 groups based on SH003 daily dose (2400, 3600, and 4800 mg); the medication will be taken orally for 21 days. The traditional 3 + 3 design will be adopted for the dose escalation. Dose-limiting toxicities are defined as grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events. The highest dose at which no more than 1 of the 6 patients experience dose-limiting toxicity will be determined as the maximum tolerated dose of SH003 combined with docetaxel. Discussion: This study investigates the safety of SH003 when combined with docetaxel. The results of this study will provide a safe dose range for conducting therapeutic exploratory trials. Trial registrations: ClinicalTrials.gov NCT04360317.

Synergistic effects of herbal medicines and anticancer drugs

“…Although herbal medicines are useful for symptom management, additionally utilizing the anticancer properties of herbal medicines tends to maximize their potential. The anticancer actions of herbal medicines are increasingly being investigated, and several studies are being performed to confirm the effects of co-administration of herbal medicines and anticancer drugs [18,19] . There is greater clarity regarding the mechanisms underlying the synergistic interactions between these agents, although further research is warranted to gain a deeper understanding of the subject [20–22] .…”

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

“…No-observed-adverse-effect level (NOAEL) of SH003 determined by phase I clinical trials was 4,800 mg/day [ 41 ]. Maximum tolerable dose (MTD) of docetaxel in cancer patients was 75 mg/m 2 [ 40 ]. Animal equivalent dose was calculated by the following equation [ 47 ]: …”

“…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).…”

State of the Art and Future Implications of SH003: Acting as a Therapeutic Anticancer Agent

“…A phase I study evaluating the maximum tolerated dose for SH003 administration alone confirmed the daily safe dose to be up to 4800 mg [ 17 ]. A clinical trial to ensure the maximum tolerated dose when administered in combination with docetaxel is also being conducted [ 18 ].…”