Description of reviewed studies

We identified 181 eligible randomized controlled clinical studies (Fig. 2). Tables 1 & 2 summarize the details of the reviewed studies. The eligible clinical trials studied 3 types of cancer (laryngeal cancer, esophageal cancer, and gastric cancer) and 3 types of precancerous lesions (oral leukoplakia, esophageal epithelial hyperplasia, and gastric precancerous lesions). In cancer treatment, 126 CHDs were used as adjuvant to conventional therapies (Table 1). Table 1 is divided into four sub-tables based on the type of conventional therapies: radiotherapy, chemotherapy, chemoradiotherapy, and targeted therapy. For the management of precancerous lesions, six CHDs were used alone, while six others were used in combination with conventional therapies (Table 2).

Fig. 2

Flow diagram of the screening process. In total, 181 clinical studies were selected for review. Low-quality study: a study in which the results do not support the authors' claims, or a study that lacks a clear description of the herbal drug composition

Table 1 Chinese herbal drugs used in combination with conventional therapiesTable 2 Chinese herbal drugs in clinical studies for managing precancerous lesions

No preclinical pharmacological or chemical studies were eligible.

Table 3 summarizes the compositions of the reviewed CHDs.

Table 3 Chinese herbal drugs reviewed

We introduce the clinical study results of CHDs listed in Table 1 & 2 under five subtitles.

Results of reviewed studiesIn patients receiving radiotherapy

Thirty-one eligible reports studied 27 CHDs in patients receiving radiotherapy. Twenty-one CHDs were tested in esophageal cancer patients, four were tested in esophageal squamous cell carcinoma (ESCC) patients, and two were tested in gastric cancer patients.

Bruceae Fructus Oil Injection, prepared with the oil derived from the fruit of Brucea javanica, is a proprietary herbal drug (PHD) approved by the National Medical Products Administration (NMPA) of China for treating cancer. It has been used in the treatment of diverse cancers for several decades [195]. In middle- and late-stage esophageal cancer patients, Bruceae Fructus Oil Injection in combination with radiotherapy significantly increased 1-year survival rate compared to radiotherapy alone (76.3% vs. 56.9%). It was also observed that the combination treatment significantly improved immune function, evidenced by increased CD4+ T cells and CD4+/CD8+ratio, and significantly reduced occurrence rate of esophagitis, compared to the mono radiotherapy. Of 76 patients, only one experienced Bruceae Fructus Oil Injection-induced fever [14]. In another study designed to assess the efficacy and safety of Bruceae Fructus Oil Injection in combination with radiotherapy in advanced esophageal cancer patients, the combination therapy exhibited higher 1-year and 2-year survival rates than single radiotherapy (1-year survival rate: 63.3% vs. 46.7%; 2-year survival rate: 33.3% vs. 20%). The combined treatment group had a higher white blood cell (WBC) count than the radiotherapy group. Among the 30 patients, only two experienced drug-associated fever [15]. Bruceae Fructus Oil Oral Liquid is an oral form PHD prepared with Bruceae Fructus Oil. In esophageal cancer patients, Bruceae Fructus Oil Oral Liquid combined with radiotherapy exhibited a higher objective response rate (ORR) than radiotherapy alone (77.5% vs. 47.5%). Patients receiving the combined therapy had a higher Karnofsky Performance Scale (KPS) score than those receiving radiotherapy alone, indicating that this PHD improved patients’ quality of life (QOL). In addition, Bruceae Fructus Oil Oral Liquid co-treatment reduced the incidence of radiotherapy-induced adverse effects, including myelosuppression (12.5% vs. 30%), nausea/vomiting (20% vs. 42.5%), as well as radiation esophagitis and pneumonitis (27.5% vs. 32.5%) [16]. Findings of these studies demonstrate that Bruceae Fructus Oil-based drugs can enhance the efficacy, and reduce the toxicities of radiotherapy, and can improve patients’ QOL in treating esophageal cancer [14, 15].

Pingxiao Tablet, an NMPA-approved anticancer drug developed based on the TCM theory of regulating blood [196], in combination with radiotherapy, significantly increased 1-, 3-, and 5-year survival rates of middle- and late-stage esophageal cancer patients compared to mono radiotherapy (1-year survival rate: 49% vs. 39.6%; 3-year survival rate: 32.1% vs. 17%; 5-year survival rate: 18.9% vs 9.4%) [17].

Huisheng Koufuye (Oral Liquid) was initially approved for treating liver and lung cancers in China [197]. A clinical trial showed that, in patients with esophageal cancer, radiotherapy plus Huisheng Koufuye (Oral Liquid) resulted in higher complete remission (CR) and 1-year survival rate compared to radiotherapy alone (CR: 71.7% vs. 45.7%; 1-year survival rate: 67.4% vs. 43.5%) [18]. Drug administration-associated adverse events were not observed in any of the 46 patients.

Irisquinone Capsule is an NMPA-approved radiosensitizer [198]. One study showed that Irisquinone Capsule plus radiotherapy group had higher 1- and 3-year survival rates than the mono radiotherapy group (1-year survival rate: 73.8% vs. 47.7%; 3-year survival rate: 35.4% vs 18.5%) in esophageal cancer patients [19]. Another study showed that Irisquinone Capsule significantly sensitized radiotherapy in esophageal cancer patients, evidenced by increased CR (combined therapy 80% vs. radiotherapy alone 40%) and 1-year survival rate (75% vs. 56.7%) [20]. In both studies, only mild gastrointestinal (GI) side effects (without affecting treatment adherence) associated with the use of Irisquinone Capsule were observed [19, 20].

Fuzheng Kangai Jiedu Formula (a 19-herb prescription created by a TCM doctor) combined with radiotherapy resulted in significantly longer progression-free survival (PFS) and median overall survival (mOS) of esophageal cancer patients than single radiotherapy (PFS: 12 months vs. 8 months; mOS: 23 months vs. 19 months). After a 4-month treatment, the combination therapy showed significantly better effects in lowering the serum levels of the tumor markers cytokeratin 19 fragment (CYFRA21-1) and glycochain antigen 19-9 (CA19-9). Moreover, the formula enhanced the immune function of esophageal cancer patients receiving radiotherapy, evidenced by increased CD3+ and CD4+ T cells, and decreased CD8+ T cells in the combined treatment group compared to those in the mono radiotherapy group [21].

Fuzheng Guben Granule (based on a 13-herb prescription created by a TCM doctor) in combination with radiotherapy achieved significantly higher CR and 1-, 3-, and 5-year survival rates in patients with middle- and late-stage esophageal cancer, compared to single radiotherapy (CR: combined therapy 62.1% vs. radiotherapy 44.0%. 1-year survival rate: 63.8% vs. 41.4%; 3-year survival rate: 29.3% vs. 14.7%; 5-year survival rate: 19.0% vs 7.6%). Meanwhile, significantly increased WBC counts, haemoglobin (Hb) content, and platelete counts, as well as significantly reduced occurrence rate of esophagitis, were observed in the combined therapy group compared to the mono radiotherapy group [22].

Aiyishu Injection is an NMPA-approved anticancer drug comprising of sodium cantharidate and vitamin B6. Combining this drug with radiotherapy significantly increased disease control rate (DCR) in patients with esophageal cancer (combined therapy 81.39% vs. radiotherapy 58.14%) [23].

Elemene Injection is an anticancer PHD comprising β-, γ-, and δ-elemene isolated from Curcumae Rhizoma. In two studies, combined use of Elemene Injection and radiotherapy resulted in a significantly higher ORR than single radiotherapy (97.5% vs. 80% [24] and 63.33% vs. 36.67% [25]) in patients with esophageal cancer. More CD4+ and CD3+ T cells, higher WBC count and CD4+/CD8+ ratio, as well as less CD8+ cells, were observed in the combined treatment group than in the mono radiotherapy group. The combination effectively lowered serum levels of the tumor markers CEA and CA19-9 more than radiotherapy alone. In addition, a higher KPS score was achieved in patients of the combination group, indicating that Elemene Injection improved QOL of patients undergoing radiotherapy [24, 25].

Fufang Danshen Injection was initially approved in China for treating coronary heart disease, angina pectoris and acute myocardial infarction. An article reported that Fufang Danshen Injection in combination with radiotherapy exhibited higher ORR than single radiotherapy in esophageal cancer patients (88.9% vs. 76.2%). It also increased the WBC count and improved the transcription activity of rDNA in the peripheral lymphocytes of patients receiving radiotherapy, indicating that it can enhance immune function of the patients [26].

Fufang Kushen Injection is an NMPA-approved anticancer adjuvant drug prepared with Sophorae Flavescentis Radix and Heterosmilacis Rhizoma. A clinical trial showed that, in patients with esophageal cancer, radiotherapy plus Fufang Kushen Injection resulted in higher CR compared to radiotherapy alone (33.3% vs. 10%). Patients in the combined treatment group exhibited better appetite, higher KPS score, and greater body weight gain than patients in the radiotherapy group, indicating that this injection improved the QOL of patients undergoing radiotherapy [27].

Fuzheng Yiliu Granule (based on a 4-herb prescription created by a TCM doctor), combined with radiotherapy resulted in a higher rosette rate of the red cell C3b receptor (RBC-C3bRR) and lower red blood cell immune complex rosette rate (RBC-ICRR) in esophageal cancer patients than single radiotherapy, indicating that it enhanced the immune function of cancer patients receiving radiotherapy. Moreover, this prescription significantly lowered the tumor metastatic marker CD44v6 in patients receiving radiotherapy [28].

Huachansu Capsule is a PHD prepared from the lipophilic components of Bufonis Corium. This drug in combination with radiotherapy achieved significantly higher ORR than single radiotherapy in treating esophageal cancer (89.47% vs. 68.42%). Meanwhile, the incidence of adverse effects (leukopenia, esophagitis, nausea, and myalgia) was lower in patients receiving the combined treatment compared to those receiving radiotherapy alone [29].

Kanglaite Injection is an NMPA-approved anticancer drug prepared from the oil of Coicis Semen. A study showed that the incidence of adverse reactions (fatigue, leukopenia and loss of appetite) caused by radiotherapy in esophageal cancer patients was significantly decreased by Kanglaite Injection [30].

Modified Liuwei Dihuang Decoction is an 8-herb prescription created by a TCM doctor. It improved the immune function of esophageal cancer patients receiving radiotherapy (CD4+/CD8+ ratio: combined therapy 1.4 vs. radiotherapy 1.2). Meanwhile, this prescription decreased the incidence of radiotherapy-induced adverse effects from 83.3% to 56.7%, and significantly improved the physical power of the patients [31].

Shenqi Liuwei Dihuang Decoction is an 8-herb prescription created by a TCM doctor. It has been shown to enhance the efficacy of radiotherapy in esophageal cancer patients. The ORR was higher in Shenqi Liuwei Dihuang Decoction plus radiotherapy group than in the mono radiotherapy group (81.8% vs. 75.5%). Patients in the combined treatment group had a lower probability of suffering from radiotherapy-induced adverse effects compared to patients in the mono-radiotherapy treatment group [32].

Si Jun Zi Tang, a classical TCM formula, is commonly used by TCM doctors for tonifying Qi. A study showed that this formula enhanced the clinical efficacy of radiotherapy in esophageal cancer patients, evidenced by an elevated ORR (combined therapy 62.5% vs. radiotherapy 37.5%) [33].

Xiangsha Bazhen Decoction is a 14-herb prescription created by a TCM doctor. This prescription has been proven to markedly increase CD4+ T cells and decrease CD8+ T cells in esophageal cancer patients receiving radiotherapy, suggesting that it enhanced the immune function of the patients. The incidence of adverse effects (vomiting and leukopenia) caused by radiotherapy was significantly reduced by the prescription [34].

In two reports, Sishen Jiedu Decoction (a 14-herb prescription created by a TCM doctor) combined with radiotherapy achieved significantly higher ORR (93.33% vs. 73.33% in one report, 92% vs. 75% in the other report) in the treatment of esophageal cancer compared to radiotherapy alone. Meanwhile, the prescription significantly reduced the occurrence rates of radiotherapy-induced adverse effects (radiation esophagitis, radiation pneumonitis, leukopenia and thrombocytopenia). QOL of patients receiving combined treatment was better than that of patients receiving radiotherapy only [35, 36].

Xuefu Zhuyu Decoction is a classical TCM formula that can protect esophageal cancer patients from radiotherapy-induced myelosuppression. Higher WBC, RBC and platelet counts were observed in the combined treatment group than in the mono radiotherapy group [37].

Yangzheng Xiaoji Capsule is a PHD that has been demonstrated to improve the QOL of esophageal cancer patients undergoing radiotherapy. The Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Oesophageal Module 18 (QLQ-OES18) symptom scores were lower in the combination treatment group than in the radiotherapy group [38].

Antike Capsule, an NMPA-approved adjuvant drug for treating ESCC, combined with radiotherapy resulted in a significantly higher ORR in the treatment of ESCC than single radiotherapy (96.9% vs. 78.1%). Clinical symptoms of the ESCC patients, including eating disorders, chest pain and back pain, disappeared more quickly in the combined treatment group than in the mono radiotherapy group. Drug treatment-associated nausea was observed [39].

Liushen Pill is another PHD that can improve the efficacy of radiotherapy in ESCC treatment. Liushen Pill in combination with radiotherapy achieved significantly higher ORR than radiotherapy alone (75.76% vs. 50.0%). It also down-regulated vascular endothelial growth factor (VEGF) expression and reduced micro-vessel density in ESCC patients receiving radiotherapy, indicating that the combination therapy exhibited better anti-angiogenic effects in ESCC patients than radiotherapy alone [40].

Astragalus Polysaccharide Injection is a PHD prepared with the TCM herb Astragali Radix. It can increase ORR in ESCC patients receiving radiotherapy (76.6% vs. 50.0%). Patients receiving combined treatment had higher KPS score and greater body weight gain than patients receiving radiotherapy alone, indicating that the injection improved patients’ QOL [41].

Lianqi Capsule is a PHD used for treating lung, liver, and esophageal cancers. In advanced ESCC patients, the combination of Lianqi Capsule and radiotherapy significantly lowered serum levels of three tumor markers (CEA, SCC-Ag, and CYFRA21-1), and showed more potent effects than radiotherapy alone. Meanwhile, this PHD improved the immune function of ESCC patients receiving radiotherapy, indicated by higher CD4+ T cell count, lower CD8+ cell count and higher CD4+/CD8+ ratio in the combined treatment group compared to the radiotherapy group [42].

Modified Fuzheng Guben Quxie Decoction (a 13-herb prescription created by a TCM doctor) combined with radiotherapy achieved longer PFS and mOS, as well as higher 1-year survival rate in stage III-IV gastric cancer treatment compared to radiotherapy alone. In the combined treatment group, serum levels of the tumor markers CEA, CA19-9, and macrophage inflammatory protein 3α (MIP-3α, also known as CCL20), and the score of patient-generated subjective global assessment (PG-SGA, a patient-reported instrument for assessment of nutritional risk and nutritional deficit in patients with cancer) were lower compared to the radiotherapy group. It was also demonstrated that CD3+ and CD4+ T cells were more, and CD4+/CD8+ ratio was higher in the combined treatment group than in the mono radiotherapy group, indicating that this herbal prescription enhanced immune function of the gastric cancer patients receiving radiotherapy [43].

Yangzheng Sanjie Decoction is a 13-herb prescription created by a TCM doctor. This decoction in combination with radiotherapy resulted in a higher DCR than radiotherapy alone (97.56% vs. 82.50%). The combination therapy more effectively lowered serum levels of three tumor markers in gastric cancer patients: CEA, VEGF, and CD44v6, compared to radiotherapy alone. Higher serum motilin level, and lower serum D-lactic acid level were observed in the combination treatment group than in the radiotherapy group, indicating that this CHD improved the GI function of patients receiving radiotherapy [44].

In patients receiving chemotherapy

A total of 114 eligible clinical studies tested the clinical use of 104 CHDs as adjuvants to chemotherapies in cancer patients (22 studies on esophageal cancer, 90 on gastric cancer, and 2 on laryngeal cancer). In one of the clinical trials, potential anticancer mechanisms of Liu Jun Zi Tang were explored. Among the 104 CHDs, 28 are NMPA-approved PHDs.

In patients receiving fluoropyrimidine-based chemotherapeutics

5-fluorouracil (5-FU) and its oral prodrugs, such as tegafur, S-1, and capecitabine, are widely used in the treatment of various cancers including upper digestive tract cancers. Twelve eligible studies reported the combinational use of individual fluoropyrimidine-based chemotherapeutics and CHDs for treating gastric cancer.

Bo-Er-Ning Capsule (BENC), derived from an 11-herb prescription, is a PHD approved as an adjuvant to cancer therapies in China. It was reported that the ORR of stage IV gastric cancer patients was higher in the group treated with the combination of BENC and S-1 than in the group treated with S-1 alone (56.67% vs. 36.67%) [45]. Forty percent of patients in the combination therapy group showed a >10% increase in KPS score, compared to 13% in the S-1 monotherapy group. The incidence of myelosuppression (23.33% vs. 50%) and GI disorders (26.67% vs. 43.33%) was lower in the combined therapy group than in the S-1 monotherapy group. This study suggests that BENC can enhance the anti-gastric cancer effects of S-1, mitigate S-1-induced side effects, and improve QOL of the patients.

Another report showed that Yangzheng Xiaoji Capsule (a PHD), combined with capecitabine, lowered serum level of the tumor marker CEA in gastric cancer patients more effectively than capecitabine alone [46]. The patients in the combination group had a higher QLQ-C30 function score compared to patients in the capecitabine monotherapy group. These results indicate that the TCM capsule enhanced the anticancer efficacy of capecitabine, and enhanced QOL of the patients.

Two clinical trials tested Shenyi Jianzhong Decoction (an 11-herb prescription created by a TCM doctor) in combination with S-1 for treating gastric cancer [47, 48]. The ORR of patients was higher in the combination group than in the S-1 group. Patients in the combination group showed a greater increase in KPS score compared to the S-1 group, indicating that this herbal prescription enhanced the anti-gastric cancer efficacy of S-1 and improved patients’ QOL.

Fuzheng Jiedu Quyu Method-based Formula (FJQR) is a 6-herb prescription from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine. FJQR combined with capecitabine improved the ORR of patients with advanced HER-2 negative gastric cancer (9.4% vs. 6.2%). The incidence of grade III-IV adverse events, including leukopenia, anemia, and nausea/vomiting, was lower in the combination group compared to the capecitabine monotreatment group [49].

Xiaoai Decoction (a 5-herb prescription created by a TCM doctor) in combination with 5-FU increased the ORR of postoperative gastric cancer patients (combination therapy vs. 5-FU alone: 89.8% vs. 75.5%) [50]. The combination therapy group showed higher 1-year (87.2% vs. 76.1%) and 2-year (19.1% vs. 10.8%) survival rates, and longer PFS (20.98 months vs. 18.71 months) and mOS (18.41 months vs. 16.51 months) compared to the 5-FU monotherapy group, indicating that Xiaoai Decoction potentiates the anticancer efficacy of 5-FU.

Some CHDs have also been shown to enhance the anticancer efficacy of fluoropyrimidines. For instance, Buyang Huanwu Tang (a classical TCM formula) combined with 5-FU resulted in a higher 5-year survival rate compared to 5-FU alone in gastric cancer patients (12.5% vs. 0%) [51]; Fufang Hongdoushan Capsule (a PHD approved as an adjuvant to cancer therapies) combined with S-1 showed increased ORR in gastric cancer patients compared to S-1 monotherapy (60% vs. 43.3%) [52]; Shenqi Jianwei Decoction (an 11-herb prescription created by a TCM doctor) combined with S-1 achieved a higher ORR in gastric cancer patients, compared to S-1 monotherapy (90% vs. 60%) [53]; and Jiawei Lizhong Decoction (a 5-herb prescription created by a TCM doctor) combined with S-1 resulted in a higher ORR compared to S-1 alone (82.22% vs. 62.22%) in gastric cancer patients, and the combination also reduced nausea and vomiting caused by S-1 [54]. The Japanese herbal medicine Hochu-ekki-to (whose composition is the same as the classical TCM formula Buzhong Yiqi Tang) was reported to reduce the occurrence of adverse events, including thrombocytopenia, nausea, vomiting, diarrhea, and appetite loss caused by S-1 treatment in stage II/III gastric cancer patients [55]. Jianpi Huazheng Decoction (a 19-herb prescription created by a TCM doctor) did not enhance the anticancer efficacy of tegafur in gastric cancer, but it was able to increase patient KPS score (the decoction + tegafur vs. tegafur alone: 72.12 vs. 65.98) [56], indicating a QOL benefit in patients.

In patients receiving CF regimen

Cisplatin in combination with 5-FU, commonly referred to as CF regimen, is one of the recommended therapies for locally advanced esophageal cancer. Six reports studied the combination of CHDs and CF regimen for treating esophageal cancer.

Sishen Jiedu Decoction combined with CF regimen resulted in a higher ORR in stage II-III esophageal cancer patients compared to CF regimen alone (90.48% vs 69.05%) [57]. The 1-year, 3-year, and 5-year survival rates of patients receiving the decoction-plus-CF regimen were 88.10%, 71.43%, and 52.38%, respectively, and those of patients who only received CF regimen were 66.67%, 45.24%, and 28.57%, respectively. The incidence of adverse effects such as leukopenia and thrombocytopenia was lower, and the KPS score was higher, in the combined treatment group than in the CF regimen group.

Another CHD that has been shown to enhance the efficacy of CF regimen is Tongguanteng Oral Solution [58], a PHD approved by the NMPA of China. Combination of this oral solution with CF regimen elevated the ORR of stage II-IV esophageal cancer patients (the oral solution + CF regimen vs. CF regimen: 75% vs. 52.5%). Patients receiving the oral solution-plus-CF regimen demonstrated a marked increase in peripheral NK cells and CD4+/CD8+ ratio, compared to the patients receiving CF regimen alone. In addition, the incidence of leukopenia, thrombocytopenia, and nausea/vomiting was significantly lower in the combined treatment group than in CF regimen group.

Xiaoaiping Tablet and Tongguanteng Oral Solution both are PHDs developed from the extracts of Caulis Marsdeniae Tenacissimae (Tongguanteng), the dry rattan stem of Marsdenia tenacissima (Roxburgh) Moon. Compared to the CF regimen alone, the combination of Xiaoaiping Tablet and CF regimen increased peripheral NK cells and CD4+/CD8+ ratio in patients with stage III-IV esophageal cancer. The tablet-plus-CF regimen decreased serum levels of tumor markers [cancer antigen 125 (CA125), CEA and CA19-9], and angiogenesis and metastasis-associated biomarkers [VEGF, transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-9 (MMP-9), and neutrophil gelatinase-associated lipocalin (NGAL)] in these patients [59]. These findings [58, 59] indicate that drugs derived from Caulis Marsdeniae Tenacissimae enhance the anticancer efficacy and reduce the adverse effects of CF regimen, and may boost immune function of the esophageal cancer patients.

Some clinical studies revealed that combining certain CHDs with CF regimen may not enhance the efficacy of CF regimen in treating esophageal cancer, but could alleviate its side effects in patients. For instance, compared to the CF regimen, Fuzheng Guben Decoction (a 13-herb prescription created by a TCM doctor) combined with CF regimen significantly reduced the incidence of vomiting (combined treatment 25% vs. CF regimen 50%), thrombocytopenia (0% vs. 12.5%), and constipation or diarrhea (0% vs. 5.2%) [60]; Xuanfu Daizhe Tang, a classical TCM formula, combined with the CF regimen decreased the occurrence of severe GI reactions (3.3% vs. 30.0%) and serious myelosuppression (6.7% vs. 33.3%) [61]; Ye Ge Yin No.2 (a 10-herb prescription created by a TCM doctor) combined with CF regimen reduced the rates of vomiting (26.7% vs. 46.7%), hepatic and renal function impairment (3.3% vs. 6.7%), and leukopenia (20% vs. 30%) [62].

The CF regimen is also utilized for treating gastric cancer. Bo-Er-Ning Capsule (BENC) in combination with CF regimen significantly prolonged mOS of stage IV gastric cancer patients (BENC + CF regimen vs. CF regimen: 23.57 months vs. 18.75 months) [63]. Higher KPS score and greater body weight gain in the BENC-plus-CF regimen group than in the TC regimen group indicated that the adjuvant therapy with BENC improved the QOL of the patients. The researchers then explored the anticancer mechanisms of BENC using the bioinformatics tool BATMAN-TCM. Enrichment analysis indicated that BENC influenced various cellular processes, including cell proliferation, cell cycle arrest, and apoptosis, which were further validated in gastric cell and/or animal models. The molecular mechanisms underlying BENC's anti-gastric cancer effects and its ability to enhance the efficacy of the CF regimen remain unclear and warrant further investigation.

In patients receiving taxanes plus platinum-based regimens

Platinum-based agents (cisplatin, carboplatin, and oxaliplatin) combined with taxanes (paclitaxel and docetaxel) are commonly used chemotherapies for treating esophageal and gastric cancers.

Shidao Tongjie Formula (a 7-herb prescription created by a TCM doctor) combined with PC regimen (paclitaxel-plus-carboplatin) improved survival in patients with stage IIb-IV esophageal cancer, compared to PC regimen alone (3-year survival rate: 48.6% vs. 25.0%) [64]. This herbal prescription combined with PC regimen increased peripheral NK cells, CD3+ cells and CD4+/CD8+ ratio compared to PC regimen alone, indicating that the herbal prescription improved the immune function of patients receiving PC regimen.

Two reports tested Shidao Tongjie Granule (a PHD with a similar herbal composition to Shidao Tongjie Formula) in combination with TP regimen (docetaxel-plus-cisplatin) for treating stage IIb-IIIc and IIb-IVb esophageal cancer [65, 66]. Patients treated with the combination of the granules and TP regimen had longer median disease-free survival (mDFS) than those treated with TP regimen alone (34.6 months vs. 23.2 months). This combination therapy also improved the ORR of the patients with stage IIb-IVb esophageal cancer (combination therapy vs. TP regimen: 55.00% vs. 32.50%), reduced chemotherapy-related adverse effects, including leukopenia, thrombocytopenia, anemia, and nausea/vomiting, and increased peripheral CD3+ cells, CD4+ cells, CD4+/CD8+ ratio, and NK cells of the patients. These studies suggest that Shidao Tongjie Formula combined with TP regimen and Shidao Tongjie Granule combined with TP regimen can serve as preferential options for treating advanced esophageal cancer.

Esophageal Pingsan, a PHD approved by NMPA as an adjuvant for treating esophageal and gastric cancers, was shown to enhance the anticancer efficacy of TP regimen in patients with stage I-III esophageal cancer (ORR: Esophageal Pingsan + TP regimen 93.33% vs. TP regimen 63.33%) [