# Comparison of Clinical Effects of Temozolomide Single Agent and Combined Doxorubicin in the Treatment of Glioma

Authors: Yibo Liu; Ligang Chen
Journal: Journal of Healthcare Engineering
 (2022)

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## Abstract

In this article, we have compared and analyzed the clinical effects of temozolomide single agent and combined doxorubicin in the treatment of glioma. To evaluate this, a total of 70 patients diagnosed with glioma in our hospital from July 2019 to July 2020 were randomly divided into two groups, the observation group and the control group, with 35 patients in each group. The control group received temozolomide capsules orally. The observation group was treated with temozolomide single agent and doxorubicin. After treatment, the clinical efficacy, adverse reactions, and KPS score of the two groups were observed. After treatment, the total response rate of the control group was 31.43%, and the total response rate of the observation group was 62.86%. The difference between the two groups was statistically significant (P<0.05). Before treatment, there was no significant difference in KPS scores between the two groups (P>0.05). After treatment, the KPS scores of both groups were improved, and the KPS scores of the observation group and the control group were significantly better, with statistical significance (P<0.05). In the observation group, 17 cases had adverse reactions, including 10 cases of nausea and vomiting, 2 cases of leucopenia, and 5 cases of thrombocytopenia, with a total incidence of 48.57%. In the control group, there were 31 cases of adverse reactions, including 22 cases of nausea and vomiting, 6 cases of leucopenia, and 4 cases of thrombocytopenia, with a total incidence of 91.43%. The difference between the two groups was statistically significant (P<0.05). The efficacy of temozolomide single agent and combined doxorubicin in the treatment of glioma was significant. Moreover, it can significantly improve clinical efficacy, reduce the incidence of adverse reactions, and improve the health status of patients, which is worthy of further clinical application.


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## Body

## 1. Introduction

Glioma is an aggressive tumor that is resistant to radiotherapy and chemotherapy, with a median survival of 12 to 15 months reported in many studies [1]. Glioma is a type of neuroepithelial tissue tumor. The incidence of WHO grade III∼IV malignant tumors have been increasing year by year in the past 30 years [2, 3]. At present, the treatment of glioma is mainly based on surgical resection [4], combined with various methods of chemotherapy and radiotherapy, interstitial chemotherapy has become one of the methods of comprehensive treatment, and its effectiveness still needs to be further confirmed [5]. At present, the patient received the most active treatment (postoperative combined radiotherapy and chemotherapy), and the survival time of the patient was less than 1 year, mainly due to GBM’s resistance to chemotherapy drugs [6]. Temozolomide is a novel oral alkylating agent antitumor agent, which plays an antitumor role mainly through DNA methylation and interference with mismatch repair mechanisms [7, 8]. Doxorubicin is a kind of cytotoxic antitumor drug commonly used in clinical practice. Its mechanism of action is mainly by inhibiting DNA polymerase, which leads to the nucleic acid cannot replicate, and then causing the apoptosis of tumor cells, thus exiting the antitumor effect [9, 10]. The purpose of this study was to investigate the clinical effect of temozolomide alone and doxorubicin in the treatment of brain glioma, and 70 patients with glioma were selected as the research objects.In this paper, we have compared and analyzed the clinical effects of temozolomide single agent and combined doxorubicin in the treatment of glioma. For this purpose, and to evaluate the expected outcomes, a total of seventy (70) patients diagnosed with glioma in our hospital, specifically from July 2019 to July 2020, were randomly divided into two groups, i.e., (i) observation group and (ii) control group, with 35 patients in each group. The control group received temozolomide capsules orally. The observation group was treated with temozolomide single agent and doxorubicin. After treatment, the clinical efficacy, adverse reactions, and KPS score of the two groups were observed. For the observation group, the dosage of temozolomide was 150 mg/(m2·d) for the first cycle, and the neutrophils and platelet counts were detected after 5 days of continuous administration.The rest of the manuscript is organized as follows.In Section2, we have discussed in detail how the patients are selected and how they are divided into various groups along with the proposed methodology which proposed the treatment. In Section 3, various results, preferably after the experiments being carried out on these different groups, are presented along with both textual and graphical explanation. Generalized discussion is provided in Section 4 of the manuscript which is followed by the concluding remarks.


## 2. Materials and Methods

### 2.1. General Information

A total of 70 patients diagnosed with glioma in our hospital from July 2019 to July 2020 were randomly divided into two groups, the observation group and the control group, with 35 patients in each group.(i)
Inclusion criteria: In line with the diagnosis of glioma in the “Standards for the Diagnosis and Treatment of Glioma (2018 Edition)” written by the Medical Administration of the National Health Commission; the individual was in good condition and can accept follow-up work; the patients and their family members were informed of this study and signed an informed consent form.(ii)
Exclusion criteria: Patients who had severe heart, liver, kidney, or blood diseases; intolerant to doxorubicin hydrochloride or temozolomide; cognitive impairment or a history of mental illness; who took the initiative to apply for withdrawal from the study.There was no significant difference between the two groups in gender, age, tumor grade, tumor location, and other general baseline data (P>0.05), and there was comparability. The general information is shown in Table 1.Table 1
The general information.
General informationObservation groupControl groupPCases3535＞0.05Age (average)50.61 ± 4.6951.67 ± 3.51＞0.05GenderBoy1920＞0.05Girl1615Tumor gradeIII2221＞0.05IV1314Tumor locationTemporal lobe1011＞0.05Frontal lobe910Parietal lobe65Occipital67Others42


### 2.2. Drug

Temozolomide: purity: >99%, batch no.:20120602; temozolomide ester, purity: >99%, batch no.:2344006, provided by Tianjin Tasly Company, dissolved and prepared with dimethyl sulfoxide into 100 mmol·mL−1 storage solution, and frozen at −20°C [11].Doxorubicin: doxorubicin hydrochloride injection was produced by Zhejiang Haisheng Pharmaceutical Co., Ltd., specification 5 M L∶10 mg, product batch number 20160725 [11].


### 2.3. Methods

In this study, all cases received chemotherapy after 2–4 weeks of total surgical resection and significant recovery of physical condition, with 28 d as a course of treatment, and 2–6 courses of chemotherapy were given according to the patient’s tolerance.Control group: temozolomide capsule, 150 mg/(m2·d) orally.Observation group: the dosage of temozolomide was 150 mg/(m2·d) for the first cycle, and the neutrophils and platelet counts were detected after 5 days of continuous administration. The dose was increased to 200 mg/(m2·d) from the beginning of the second cycle without significant hematotoxicity. Combined doxorubicin was injected with diluted doxorubicin hydrochloride by the attending physician with intermittent Ommaya pumps. Doxorubicin was given for 6 to 8 weeks at a dose of 1 to 5 mg per dose, depending on the dose and concentration of the case’s response during chemotherapy.


### 2.4. Efficacy Evaluation Criteria

Efficacy was evaluated according to Alexandra and so on [12], to formulate the following rules: complete response: the case’s lesion disappeared completely without recurrence for more than 4 weeks; partial response: tumor volume reduction of more than 50%; improvement: no new lesions were observed, and the tumor volume was reduced by 25% na-50%; stability: the tumor volume was reduced or increased but the range was less than 25%, and no new lesions; and progression: new lesions, or tumor volume increase 25% or more.Total response rate = (complete response + partial response)/total cases × 100%.


### 2.5. Observational Index

The observation indexes included clinical efficacy, KPS score, and adverse reactions, as follows:(1)
Clinical efficacy: According to the efficacy evaluation criteria of Alexandra et al., the clinical efficacy evaluation criteria were divided into complete response, partial response, improvement, stability, and progress.(2)
KPS score: The Karnofsky functional status score [13] was used to evaluate the health status of patients before and after treatment. The total score was 0–100. The higher the score, the better the health status of patients.(3)
Adverse reactions: The adverse reactions of nausea and vomiting, leucopenia, and thrombocytopenia during treatment were observed and counted.


### 2.6. Adverse Reaction Observation

The adverse reactions such as nausea and vomiting, leucopenia, and thrombocytopenia during the treatment were observed and counted.


### 2.7. Statistical Method

All count data in this study were processed by SPSS 20.0 statistical software and expressed in the form of a percentage. The Chi-square test was performed for comparison between groups, andP<0.05 was considered statistically significant.


## 2.1. General Information

A total of 70 patients diagnosed with glioma in our hospital from July 2019 to July 2020 were randomly divided into two groups, the observation group and the control group, with 35 patients in each group.(i)
Inclusion criteria: In line with the diagnosis of glioma in the “Standards for the Diagnosis and Treatment of Glioma (2018 Edition)” written by the Medical Administration of the National Health Commission; the individual was in good condition and can accept follow-up work; the patients and their family members were informed of this study and signed an informed consent form.(ii)
Exclusion criteria: Patients who had severe heart, liver, kidney, or blood diseases; intolerant to doxorubicin hydrochloride or temozolomide; cognitive impairment or a history of mental illness; who took the initiative to apply for withdrawal from the study.There was no significant difference between the two groups in gender, age, tumor grade, tumor location, and other general baseline data (P>0.05), and there was comparability. The general information is shown in Table 1.Table 1
The general information.
General informationObservation groupControl groupPCases3535＞0.05Age (average)50.61 ± 4.6951.67 ± 3.51＞0.05GenderBoy1920＞0.05Girl1615Tumor gradeIII2221＞0.05IV1314Tumor locationTemporal lobe1011＞0.05Frontal lobe910Parietal lobe65Occipital67Others42


## 2.2. Drug

Temozolomide: purity: >99%, batch no.:20120602; temozolomide ester, purity: >99%, batch no.:2344006, provided by Tianjin Tasly Company, dissolved and prepared with dimethyl sulfoxide into 100 mmol·mL−1 storage solution, and frozen at −20°C [11].Doxorubicin: doxorubicin hydrochloride injection was produced by Zhejiang Haisheng Pharmaceutical Co., Ltd., specification 5 M L∶10 mg, product batch number 20160725 [11].


## 2.3. Methods

In this study, all cases received chemotherapy after 2–4 weeks of total surgical resection and significant recovery of physical condition, with 28 d as a course of treatment, and 2–6 courses of chemotherapy were given according to the patient’s tolerance.Control group: temozolomide capsule, 150 mg/(m2·d) orally.Observation group: the dosage of temozolomide was 150 mg/(m2·d) for the first cycle, and the neutrophils and platelet counts were detected after 5 days of continuous administration. The dose was increased to 200 mg/(m2·d) from the beginning of the second cycle without significant hematotoxicity. Combined doxorubicin was injected with diluted doxorubicin hydrochloride by the attending physician with intermittent Ommaya pumps. Doxorubicin was given for 6 to 8 weeks at a dose of 1 to 5 mg per dose, depending on the dose and concentration of the case’s response during chemotherapy.


## 2.4. Efficacy Evaluation Criteria

Efficacy was evaluated according to Alexandra and so on [12], to formulate the following rules: complete response: the case’s lesion disappeared completely without recurrence for more than 4 weeks; partial response: tumor volume reduction of more than 50%; improvement: no new lesions were observed, and the tumor volume was reduced by 25% na-50%; stability: the tumor volume was reduced or increased but the range was less than 25%, and no new lesions; and progression: new lesions, or tumor volume increase 25% or more.Total response rate = (complete response + partial response)/total cases × 100%.


## 2.5. Observational Index

The observation indexes included clinical efficacy, KPS score, and adverse reactions, as follows:(1)
Clinical efficacy: According to the efficacy evaluation criteria of Alexandra et al., the clinical efficacy evaluation criteria were divided into complete response, partial response, improvement, stability, and progress.(2)
KPS score: The Karnofsky functional status score [13] was used to evaluate the health status of patients before and after treatment. The total score was 0–100. The higher the score, the better the health status of patients.(3)
Adverse reactions: The adverse reactions of nausea and vomiting, leucopenia, and thrombocytopenia during treatment were observed and counted.


## 2.6. Adverse Reaction Observation

The adverse reactions such as nausea and vomiting, leucopenia, and thrombocytopenia during the treatment were observed and counted.


## 2.7. Statistical Method

All count data in this study were processed by SPSS 20.0 statistical software and expressed in the form of a percentage. The Chi-square test was performed for comparison between groups, andP<0.05 was considered statistically significant.


## 3. Results of Experiments

### 3.1. Comparison of Clinical Efficacy

After treatment, the total response rate of the control group was 31.43%, and the total response rate of the observation group was 62.86%. The difference between the two groups was statistically significant (P<0.05). Comparison of clinical efficacy is shown in Table 2.Table 2
Comparison of clinical efficacy.
GroupsCasesComplete responsePartial responseImprovementStabilityProgressionTotal response rateObservation group3561647262.86%Control group3529106831.43%P＜0.05＜0.05＜0.05＜0.05＜0.05＜0.05


### 3.2. Comparison of KPS Score

Before treatment, there was no significant difference in KPS scores between the two groups (P>0.05). After treatment, the KPS scores of both groups were improved, and the KPS scores of the observation group and the control group were significantly better, with statistical significance (P<0.05). Comparison of KPS score is shown in Table 3.Table 3
Comparison of KPS score.
GroupsObservation groupControl grouptPKPS scoreBefore treatment63.15 ± 4.2364.08 ± 4.370.940＞0.05After treatment86.71 ± 8.6471.34 ± 6.558.352＜0.05


### 3.3. Comparison of Adverse Reactions

In the observation group, 17 cases had adverse reactions, including 10 cases of nausea and vomiting, 2 cases of leucopenia, and 5 cases of thrombocytopenia, with a total incidence of 48.57%. In the control group, there were 31 cases of adverse reactions, including 22 cases of nausea and vomiting, 6 cases of leucopenia, and 4 cases of thrombocytopenia, with a total incidence of 91.43%. The difference between the two groups was statistically significant (P<0.05). Comparison of adverse reactions is shown in Table 4.Table 4
Comparison of adverse reactions.
GroupsCasesNausea and vomitingLeucopeniaThrombocytopeniaTotal incidenceObservation group35102548.57%Control group35226491.43%P＜0.05＜0.05＜0.05＜0.05


## 3.1. Comparison of Clinical Efficacy

After treatment, the total response rate of the control group was 31.43%, and the total response rate of the observation group was 62.86%. The difference between the two groups was statistically significant (P<0.05). Comparison of clinical efficacy is shown in Table 2.Table 2
Comparison of clinical efficacy.
GroupsCasesComplete responsePartial responseImprovementStabilityProgressionTotal response rateObservation group3561647262.86%Control group3529106831.43%P＜0.05＜0.05＜0.05＜0.05＜0.05＜0.05


## 3.2. Comparison of KPS Score

Before treatment, there was no significant difference in KPS scores between the two groups (P>0.05). After treatment, the KPS scores of both groups were improved, and the KPS scores of the observation group and the control group were significantly better, with statistical significance (P<0.05). Comparison of KPS score is shown in Table 3.Table 3
Comparison of KPS score.
GroupsObservation groupControl grouptPKPS scoreBefore treatment63.15 ± 4.2364.08 ± 4.370.940＞0.05After treatment86.71 ± 8.6471.34 ± 6.558.352＜0.05


## 3.3. Comparison of Adverse Reactions

In the observation group, 17 cases had adverse reactions, including 10 cases of nausea and vomiting, 2 cases of leucopenia, and 5 cases of thrombocytopenia, with a total incidence of 48.57%. In the control group, there were 31 cases of adverse reactions, including 22 cases of nausea and vomiting, 6 cases of leucopenia, and 4 cases of thrombocytopenia, with a total incidence of 91.43%. The difference between the two groups was statistically significant (P<0.05). Comparison of adverse reactions is shown in Table 4.Table 4
Comparison of adverse reactions.
GroupsCasesNausea and vomitingLeucopeniaThrombocytopeniaTotal incidenceObservation group35102548.57%Control group35226491.43%P＜0.05＜0.05＜0.05＜0.05


## 4. Discussion

Glioma is one of the malignant tumors with high mortality in clinical practice. The survival period of this disease is very short, and the treatment is difficult, even if the tumor tissue has been surgically removed under the naked eye [14, 15], however, due to the growth characteristics of the tumor cells themselves, there are still a few in the surrounding normal tissue, so the surgery has a very high recurrence rate [16]. Therefore, how to further kill tumor cells and prevent their recurrence through more effective chemotherapy drugs after surgery is of great significance [17]. In recent years, temozolomide, as a new type of alkylating agent antitumor drug, has begun to enter the clinic and is gradually used in the first-line chemotherapy for malignant tumors such as glioma [18, 19]. The bioavailability of the drug is close to 100%, and it can be quickly absorbed after oral administration, without liver metabolism, and quickly passes through the blood-brain barrier to achieve the effect of antiglioma [20]. Doxorubicin, also known as 14-hydroxydaunorubicin, is a broad-spectrum antitumor antibiotic, which can inhibit the synthesis of RNA and DNA. It mainly inhibits nucleic acid synthesis by embedding DNA, and then plays an antitumor effect. It has a significant therapeutic effect on a variety of tumors in clinical practice [21]. The doxorubicin interstitial chemotherapy refers to the intraoperative injection of biodegradable polymers into the intraoperative lumen after tumor resection, which can be repeated many times after the operation to inject drugs into the embedded subcutaneous chemotherapy capsule, which can be repeated many times [22].After treatment, the total response rate of the control group was 31.43%, and the total response rate of the observation group was 62.86%. The difference between the two groups was statistically significant (P<0.05). Before treatment, there was no significant difference in KPS scores between the two groups (P>0.05). After treatment, the KPS scores of both groups were improved, and the KPS scores of the observation group and the control group were significantly better, with statistical significance (P<0.05). In the observation group, 17 cases had adverse reactions, including 10 cases of nausea and vomiting, 2 cases of leucopenia, and 5 cases of thrombocytopenia, with a total incidence of 48.57%. In the control group, there were 31 cases of adverse reactions, including 22 cases of nausea and vomiting, 6 cases of leucopenia, and 4 cases of thrombocytopenia, with a total incidence of 91.43%. The difference between the two groups was statistically significant (P<0.05).In conclusion, the efficacy of temozolomide single agent and combined doxorubicin in the treatment of glioma was significant. Moreover, it can significantly improve clinical efficacy, reduce the incidence of adverse reactions and improve the health status of patients, which is worthy of further clinical application.


## 5. Conclusion and Future Work

In this article, we have compared and analyzed the clinical effects of temozolomide single agent and combined doxorubicin in the treatment of glioma. To evaluate this, a total of 70 patients diagnosed with glioma in our hospital from July 2019 to July 2020 were randomly divided into two groups, the observation group and the control group, with 35 patients in each group. The control group received temozolomide capsules orally. The observation group was treated with temozolomide single agent and doxorubicin. After treatment, the clinical efficacy, adverse reactions, and KPS score of the two groups were observed. After treatment, the total response rate of the control group was 31.43%, and the total response rate of the observation group was 62.86%. The difference between the two groups was statistically significant (P<0.05). The efficacy of temozolomide single agent and combined doxorubicin in the treatment of glioma was significant. Moreover, it can significantly improve clinical efficacy, reduce the incidence of adverse reactions and improve the health status of patients, which is worthy of further clinical application.This work can be further extended to examine the clinical effects of other treatment schemes and methodologies.



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*Source: 7995385-2022-03-19.xml*