Clinical observation of Shengxuebao Mixture in treating anemia after concurrent chemoradiotherapy for cervical cancer

Kai Zhou, Jia-Yu Zhang, Xi-Wei Yang, Da Shen, Jun-Jin Li, Yan-Fang Cheng, Xiao-ling Qian, Pei-Xian Zhang, 4*

Clinical observation of Shengxuebao Mixture in treating anemia after concurrent chemoradiotherapy for cervical cancer

Kai Zhou1, Jia-Yu Zhang1, Xi-Wei Yang1, Da Shen2, Jun-Jin Li3, Yan-Fang Cheng3, Xiao-ling Qian3, Pei-Xian Zhang3, 4*

1The First Clinical Medical College of Yunnan University of Traditional Chinese Medicine, Kunming 650051, Yunnan, China;2The People’s Hospital of Shilin, Shilin 652200, Yunnan, China;3Department of Oncology, Yan’an Hospital Affiliated to Kunming Medical University, Kunming 650051, Yunnan, China;4Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming 650051, Yunnan, China.

To investigate the efficacy of the Shengxuebao Mixture in treating anemia after concurrent chemoradiotherapy for cervical cancer.The patients who met the criteria were randomly divided into the study group (n = 30) and the control group (n = 30). The study group was treated with Shengxuebao Mixture （15 ml once, three times a day）for 30 days, and the control group was treated with ferrous succinate tablets (0.1 g, twice a day), folic acid tablets (5 mg, three times a day), and vitamin B12 tablets (25 μg, once a day) for 30 days. Observed the hemoglobin level, erythropoietin level, TCM syndrome score, karnofsky performance status score before and after treatment in the two groups, compared the relevant data and clinical efficacy between the two groups and observed the adverse drug reactions at the same time.The age, pathological type, stage, baseline hemoglobin level, erythropoietin level, TCM syndrome score, and karnofsky performance status score were comparable between the two groups (> 0.05). The hemoglobin level of the two groups after treatment was higher than before treatment (< 0.05). After treatment, the hemoglobin level in the study group was significantly higher than that in the control group (< 0.05), and the number of effective cases in the study group was more than that in the control group, and the effective rate in the study group was higher than that in the control group (< 0.05). The erythropoietin level of the two groups after treatment was lower than before treatment (< 0.05). After treatment, the erythropoietin level in the study group was significantly lower than that in the control group (< 0.05). The TCM syndrome score of the study group decreased significantly after treatment (< 0.05), but there was no significant change in the control group (> 0.05). After treatment, the TCM syndrome score of the study group was significantly lower than that of the control group (< 0.05), and the number of effective cases in the study group was more than that in the control group, and the effective rate in the study group was higher than that in the control group (< 0.05). There was no significant change in the karnofsky performance status score of the study group after treatment (> 0.05), but the karnofsky performance status score of the control group decreased significantly (< 0.05). After treatment, the karnofsky performance status score of the study group was higher than that of the control group (< 0.05), and the number of effective cases in the study group was more than that of the control group, and the effective rate was higher than that of the control group (< 0.05). And there were no obvious adverse reactions in this study.To some extent, this study showed that the Shengxuebao Mixture has a definite effect in treating anemia after concurrent chemoradiotherapy for cervical cancer, can promote the use of erythropoietin, improve TCM syndromes and stabilize the quality of life of patients.

Shengxuebao Mixture, Cervical cancer, Concurrent chemoradiotherapy, Anemia

Background

Cancer-related anemia (CRA) refers to anemia caused by the cancer itself or its treatment [1]. A European survey involving about 15000 patients in 24 countries found that CRA incidence was 39.30%, of which gynecological cancer-related anemia was widespread [2]. CRA patients often show dizziness, palpitation, fatigue, drowsiness, and even shortness of breath and death [3], which has become an independent factor affecting the prognosis of patients [4]. It significantly reduces the quality of life of patients and the efficacy of radiotherapy and chemotherapy. At present, the degree of attention to CRA is insufficient, Western medicine mainly uses blood transfusion, erythropoietin (EPO), iron agent, but there are some problems, such as blood transfusion infection, thrombus risk, gastrointestinal reaction, and so on. Traditional Chinese Medicine (TCM) believes that CRA belongs to the category of "blood deficiency". It has achieved certain curative effects by tonifying spleen and kidney and Qi and blood. The prescription of Shengxuebao Mixture is rooted in the correlation of Qi and blood and the mutualization of essence and blood. It has a good effect on the syndrome of liver and kidney deficiency and Qi and blood deficiency. Therefore, this study aimed at patients with anemia after concurrent chemoradiotherapy for cervical cancer, and explored the efficacy of Shengxuebao Mixture in the treatment of CRA, and provided clinical evidence.

Materials and methods

General information

This study was a prospective study. Sixty-four cervical cancer patients with anemia after concurrent chemoradiotherapy in the Department of Oncology, Yan'an Hospital affiliated to Kunming Medical University from January 2020 to January 2021 were selected, and 4 cases lost follow-up because of loss of follow-up. Finally, 60 cases were randomly divided into study group (n = 30) and control group (n = 30). The average age of the study group was 52.27 ± 10.49 years old, including 5 cases of adenocarcinoma, 25 cases of squamous cell carcinoma, 8 cases of II stage, 14 cases of III stage, and 8 cases of IV stage. The average age of the control group was 53.07 ± 11.30 years old, including 6 cases of adenocarcinoma, 24 cases of squamous cell carcinoma, 9 cases of II stage, 13 cases of III stage, and 8 cases of IV stage. The age, pathological type, stage, baseline hemoglobin (Hb) level, EPO level, TCM syndrome score, and karnofsky performance status (KPS) score of the two groups were comparable. All patients signed informed consent.

Diagnostic criteria

Diagnostic criteria of Western Medicine. Anemia and anemia degree were diagnosed according to World Health Organization (WHO) standard: normal (≥ 110g/L), mild (95-109 g/L), moderate (80-94 g/L), severe (65-79 g/L), extremely severe (< 65 g/L).

Diagnostic criteria of TCM. The standard of Yin deficiency of liver and kidney was drawn up according to the Guiding Principles of Clinical Research of New Drugs of Traditional Chinese Medicine [5] and "Diagnostics of Traditional Chinese Medicine" [6]. The main symptoms were sore waist and knees, upset and fever, dizziness, tinnitus.And secondary symptoms were insomnia, hot flashes and night sweats, dry mouth and pharynx, forgetfulness. Including at least two kinds main symptom (necessary for sore waist and knees) and at least two kinds secondary symptoms each can be diagnosed with reference to tongue and pulse conditions.

Inclusion criteria

Patients with cervical cancer after concurrent chemoradiotherapy in IIB-IVA stage. TCM syndrome was liver and kidney Yin deficiency; the degree of anemia was mild to moderate; KPS score ≥ 60; age was 30-75 years old; expected survival time was more than three months; EPO and blood transfusion had not been used in nearly one month.

Exclusion criteria

Did not meet the inclusion criteria; allergic to drug used in this test; had heart, liver, kidney, brain, and other vital organ dysfunction; can not cooperate with this test.

Treatment methods

The study group was treated with Shengxuebao Mixture（15 ml once, three times a day）for 30 days, and the control group was treated with ferrous succinate tablets (0.1 g, twice a day), folic acid tablets (5 mg, three times a day), and vitamin B12 tablets (25 μg, once a day) for 30 days.

Observation index

The levels of Hb, EPO, TCM syndrome score, KPS score, and adverse drug reactions were observed in the two groups before and after treatment.

Evaluation criteria of curative effect

Refered to the Diagnosis and Efficacy Criteria for Hematologic Diseases [7] to determine the efficacy of the treatment of anemia, effective: Hb level returned to normal (≥ 110 g/L); ineffective: Hb level did not return to normal. According to the Guiding Principles of Clinical Research of New Drugs of Traditional Chinese Medicine [5] to judge the curative effect standard of TCM syndrome, cured: the symptoms and signs of the syndrome disappeared or nearly disappeared, and the score decreased by ≥ 95%; significantly effective: the symptoms and signs of the syndrome were significantly improved, the score decreased by ≥ 70%; effective: the symptoms and signs of the syndrome were improved, and the score decreased by ≥ 30%; ineffective: the symptoms and signs of the syndrome did not significantly improve or even aggravated, and the score decreased by less than 30%. Effective cases = cured cases + significantly effective cases + effective cases, ineffective cases = total cases-effective cases, effective rate = (effective cases/total cases) x 100%, ineffective rate = 1 - effective rate. According to the KPS score standard to determine the efficacy of quality of life, improved: after treatment, the score increased by ≥ 10 points; stable: there was no change after treatment; decreased: after treatment, the score decreased by ≥ 10 points. Effective cases = improved cases + stable cases, ineffective cases = decreased cases, effective rate = (effective cases/total cases) x 100%, inefficiency = 1- effective rate.

Statistical methods

The data were processed by SPSS22.0 software, the measurement data were processed by t-test or Mann-Whitney test, and the counting data were processed by χ2test.< 0.05 is statistically significant.

Results

Comparison of curative effect of anemia (Table 1)

Comparison of EPO level (Table 2)

Comparison of TCM syndrome (Table 3)

Comparison of quality of life (Table 4)

Security comparison

No obvious adverse reactions were found in the two groups. there were no obvious adverse reactions in this study

Table 1 Comparison of curative effect of anemia

NOTE. The hemoglobin level of the two groups after treatment was higher than before treatment (< 0.05). After treatment, the hemoglobin level in the study group was significantly higher than that in the control group (< 0.05), and the number of effective cases in the study group was more than that in the control group, and the effective rate in the study group was higher than that in the control group (< 0.05).

Table 2 Comparison of erythropoietin level

NOTE. The erythropoietin level of the two groups after treatment was lower than before treatment (< 0.05). After treatment, the erythropoietin level in the study group was significantly lower than that in the control group (< 0.05).

Table 3 Comparison of Traditonal Chinese Medicine syndrome

NOTE. The Traditonal Chinese Medicine syndrome score of the study group decreased significantly after treatment (< 0.05), but there was no significant change in the control group (> 0.05). After treatment, the Traditonal Chinese Medicine syndrome score of the study group was significantly lower than that of the control group (< 0.05), and the number of effective cases in the study group was more than that in the control group, and the effective rate in the study group was higher than that in the control group (< 0.05).

Table 4 Comparison of quality of life

NOTE. There was no significant change in the karnofsky performance status score of the study group after treatment (> 0.05), but the karnofsky performance status score of the control group decreased significantly (< 0.05). After treatment, the karnofsky performance status score of the study group was higher than that of the control group (< 0.05), and the number of effective cases in the study group was more than that of the control group, and the effective rate was higher than that of the control group (< 0.05).

Discussion

Cervical cancer is a common gynecological malignant tumor, and concurrent chemoradiotherapy is one of its main treatment methods. CRA incidence in patients with cervical cancer is high, and the rate and degree of anemia will further increase after concurrent chemoradiotherapy. The hypoxic microenvironment caused by anemia leads to the resistance of tumor cells to treatment, so we should pay attention to the mechanism and treatment of CRA. In terms of mechanism, the occurrence of CRA is mainly due to insufficient production, destruction, and loss of Red Blood Cell (RBC) [1]. The insufficient production of RBC is related to the following factors: lack of nutrition, bone marrow suppression, and bone marrow infiltration, and kidney injury caused by chemotherapeutic drugs [8, 9]. The destruction of RBC is related to immune hemolysis, which is common in lymphoma [10]. The loss of RBC is related to surgical blood loss and tumor bleeding [11]. At present, Western medicine is mainly treated with blood transfusion, EPO, and iron, which has a good therapeutic effect on different degrees of anemia and takes effect quickly. However, Western medicine treatment mostly acts on a single link of hematopoiesis, and the long-term benefit of patients is not observable. There are also some problems, such as high cost, blood transfusion infection, risk of thrombus, gastrointestinal reaction, drug resistance of tumor cells, disease progression, and even death. [12-16]. CRA belongs to the category of "blood deficiency" in Traditional Chinese Medicine. Cancer toxin and various therapeutic measures damage the spleen and kidney and affect blood metaplasia. Patients feel dizzy, less gas lazy words, fatigue. Based on the understanding of Traditional Chinese Medicine, its main pathogenesis is spleen and kidney and Qi and blood deficiency, so tonifying spleen and kidney and Qi and blood is obviously effective in increasing the concentration of Hb and improving anemia syndrome. It has been proved that a variety of traditional Chinese medicine can promote hematopoiesis.

In Shengxuebao Mixture, Heshouwu () is made to tonify liver and kidney, nourish essence and blood, warm but not greasy, and Huangqi () is used to nourish Qi and blood. The two drugs are the sovereign drug, which acts on the central syndrome of deficiency of liver and kidney and deficiency of both Qi and blood. Nüzhenzi () nourishes liver and kidney, and Mohanlian () nourishes liver and kidney, Sangshen () nourishes Yin and blood, the 3 drugs are minister drug. Baishao () nourishes blood and Yin, calms liver-Yang, Gouji () tonifies liver and kidney, strengthens muscles and bones and can enhance blood concentration, they are assistant drug and envoy drug. The seven drugs are properly matched, it nourishes liver blood and kidney Qi, it makes the essence and blood reproduce and transform each other. So it can improve the symptoms related to Yin deficiency of liver and kidney, and has a good effect on the treatment of anemia.

EPO is mainly secreted by the kidney and can regulate the production of RBC and the supply of oxygen. It is generally negatively correlated with the level of Hb. In this study, the EPO levels in both groups were higher before treatment and decreased after treatment, which may be related to the anemia status. The EPO level in the study group was significantly lower than that in the control group after treatment, and the curative effect of anemia was better than that in the control group, probably because the Shengxuebao Mixture could improve the utilization of EPO and improve anemia to some extent. Studies have found that Astragalus polysaccharides can promote EPO expression [17], Radix Paeoniae Alba can increase the level of EPO to regulate hematopoiesis [18]. Polignum multiflorum polysaccharide can promote the proliferation of erythroid progenitor cells and stimulate hematopoiesis [19].

The results of this study showed that after treatment, the level of Hb and the therapeutic effect of anemia in the study group were better than those in the control group, the level of EPO in the study group was lower than that in the control group, the score of TCM syndrome in the study group was lower than that in the control group, the curative effect of improving TCM syndromes is better than that of the control group, and the score of quality of life in the study group was higher than that in the control group, the curative effect to stable quality of life is better than the control group, no obvious adverse reactions were seen. To sum up, to some extent this study showed that the Shengxuebao Mixture has a definite effect in treating anemia after concurrent chemoradiotherapy for cervical cancer, can promote the use of EPO, improve TCM syndromes and stabilize the quality of life of patients. However, due to the limited time and sample size, it is necessary to study further the specific mechanism of improving anemia.

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10.12032/TMRCR20210507005

Pei-Xian Zhang, Yan'an Hospital Affiliated to Kunming Medical University, No. 245, Renmin East Road, Panlong District, Kunming, China. E-mail: CR18192021@163.com

CRA, cancer-related anemia; EPO, erythropoietin; TCM, Traditional Chinese Medicine; Hb, hemoglobin; KPS, karnofsky performance status; WHO, World Health Organization; RBC, Red Blood Cell.

:The authors declare that they have no conflict of interest.

: Zhou K, Zhang JY, Yang XW, et al. Clinical observation of Shengxuebao Mixture in treating anemia after concurrent chemoradiotherapy for cervical cancer2021;4(2):5.

:Ying Chen.

:29 March 2021,

30 April 2021,

:07 May 2021

? 2021 By Authors. Published by TMR Publishing Group Limited. This is an open access article under the CC-BY license (http://creativecommons.org/licenses/BY/4.0/).