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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 5  |  Page : 46-51

Kanglaite injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma


1 Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China
2 Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China
3 Department of Oncology, Shandong University Affiliated Jinan Central Hospital, Jinan 250013, China
4 Department of Emergency, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China
5 Department of Epidemiology, Xinxiang Medical University, Xinxiang 453100, China

Date of Web Publication30-Aug-2014

Correspondence Address:
Xiaoge Kou
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.139758

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 > Abstract 

Objective: To evaluate the clinical efficacy of Kanglaite (KLT) injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma (NSCLC) by meta-analysis.
Materials and Methods: Electronic search of PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases was conducted to select studies about KLT injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced NSCLC. The pooled risk ratio (RR) and its 95% confidence interval (95% CI) for objective response rate (ORR), Karnofsky (KPS) score improvement and nausea and vomiting were calculated by Stata11.0 statistical software.
Result: Finally, we included 34 clinical trials in this meta-analysis. The pooled results suggested that KLT injection combined with systematic chemotherapy can significantly increase the objective response rate (ORR) [RR = 1.35, 95% CI: 1.23-1.48, (Z = 6.43, P = 0.000)], the quality of patients' life (KSP improvement) [RR = 2.04, 95% CI: 1.79-2.33, (Z = 10.57, P = 0.000)] and decrease the risk ratio of gastrointestinal reaction [RR = 0.53, 95% CI: 0.42-0.66, (Z = 5.53, P = 0.000)] compared with chemotherapy alone.
Conclusion: KLT injection combined with chemotherapy can improve the short-term efficacy, performance status and decrease the risk of gastrointestinal reaction compared with systematic chemotherapy alone.

Keywords: Chemotherapy, clinical efficacy, Kanglaite, meta-analysis, non-small cell lung carcinoma


How to cite this article:
Liu X, Yang Q, Xi Y, Yu K, Wang W, Zhao X, Kou X. Kanglaite injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma. J Can Res Ther 2014;10, Suppl S1:46-51

How to cite this URL:
Liu X, Yang Q, Xi Y, Yu K, Wang W, Zhao X, Kou X. Kanglaite injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma. J Can Res Ther [serial online] 2014 [cited 2020 Feb 17];10:46-51. Available from: http://www.cancerjournal.net/text.asp?2014/10/5/46/139758


 > Introduction Top


Lung cancer is leading cause of cancer related death and most commonly diagnosed cancer globally in year 2008 according to the world cancer statistics. [1] Generally, lung cancer is divided non-small lung cancer (NSCLC) and small cell lung carcinoma (SCLC) according to the pathology. The NSCLC accounting for 75%-80% lung cancer diagnosed is subdivided into squamous cell lung carcinoma, adenocarcinoma, and big cell lung carcinoma. [2],[3] In China, NSCLC is the most commonly diagnosed solid carcinoma and the first leading cause of cancer-related death in male and second leading cause in female. Patients with early stage of NSCLC can be treated by surgery with relative acceptable prognosis and patients with advanced or metastasis stage of this disease could be only treaded with systematic chemoradiation. In advanced-stage NSCLC, chemotherapy can prolong survival and improves patient quality of life, but its effectiveness is not completely satisfactory. And based on the cisplatin (DDP) and third generation chemotherapy regimen, the objective response rate was only 20%-30%.

Kanglaite (KLT) injection is a unique botanically sourced molecular targeted agent prepared as a micro-emulsion for intravenous use. Several clinical studies indicated the KLT combined with systematic chemotherapy can improve the clinical efficacy in patients with several types of carcinoma.

But with relatively small patients number included in each study, the statistical power is limited. Thus, we performed this meta-analysis to further demonstrate the clinical efficacy of KLT in the treatment of NSCLC by meta-analysis.


 > Materials and methods Top


Literature source and search strategy

We searched and extracted eligible studies about KLT injection assistant treatment of NSCLC by searching databases of PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases. The combination of the following key words were used: "lung cancer", "lung carcimoma", "non-small cell lung cancer", "non-small lung carcinoma", "NSCLC", "Kanglaite" and "KLT".

Inclusion and exclusion criteria

The following criteria were used for the literature inclusion: (a): The study design was confined to prospective clinical controlled trials with or without blind; (b) The patients was pathologically confirmed non-small lung carcinoma; (c) The intervention was KLT injection combined with systematic chemotherapy; (d) The control group was only given systematic chemotherapy; (f) The outcome should include the objective response rate, the KPS improvement and gastrointestinal reaction incidence rate. The major exclusion were: (a) Overlapping study populations; (b) Retrospectively studied; (c) patients without pathology confirmed; (d) Without detailed data about objective response rate, the KPS improvement and gastrointestinal reaction incidence rate.

Data extraction and quality evaluation

The general characteristics of the included trials were extracted such as first author name, publication time, number of subjects in the treatment and control arms and detailed treatments regimen. The frequency for interested events in the combined treatment and control groups were extracted carefully. The general methodological quality of each included trials was evaluated by a six-questionnaire according to the Cochrane protocol when evaluation of clinical randomized trials. The question questions are: (a) Adequate sequence gereration? (b) Allocation concealment? (c) Incomplete outcome data addressed? (d) Free of selective reporting? (f) Free of other bias?

Response criteria

According to the Response Evaluation Criteria in Solid Tumors (RECST) developed by the World Health Organization (WHO), [4] the tumor response were divided to complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The objective response rate was definite as CR + PR. And the exact definition for CR, PR, SD and PD was as follows: CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the  Longest diameter (LD) of target lesions, taking as reference the baseline sum LD; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started; PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Statistical method

All of the data was pooled and calculated by STATA11.0 software. The risk ratio was used to analyze dichotomous data. If heterogeneity was found across the trials the pooled results was calculated based on random effect model; otherwise, if there was no statistical heterogeneity was found across the included studies, the fixed effect model was used. Heterogeneity was tested using the Z score and χ2 in which P < 0.1 was considered statistically significant.


 > Results Top


General characteristics of included trials

Finally, 34 trials [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38] on KLT injection combined with systematic chemotherapy versus chemotherapy alone in the treatment of NSCLC were included in this meta-analysis. The general characteristics of included trials were showed in [Table 1]. The most common use chemotherapy regimens were NP, GP, EP and MVP. The general methodological quality of each included trials was relative low which was demonstrated in [Figure 1].
Figure 1: The quality assessment of included trials

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Table 1: The general characteristics of included studies

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Objective response rate

Twenty-nine studies reported the objective response rate in each arm. The heterogeneity analysis showed no significant heterogeneity was found (I 2 = 0.00%, P = 0.886) and the pooled RR for ORR was RR = 1.35, 95% CI: 1.23--1.48, (Z = 6.43, P = 0.000), [Figure 2]. The pooled results indicated that KLT injection combined systematic chemotherapy can significant increase the short-term efficacy for patients with NSCLC compared with chemotherapy alone.
Figure 2: Forest plot for the objective response

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KPS improvement

Nineteen studies reported the KPS improvement with significant heterogeneity across the trials (I 2 = 62.0%, P = 0.00). The data pooled based on randomized effect model demonstrated that combined treatment can significant improve the patients quality of life [RR = 2.04, 95% CI: 1.79-2.33, (Z = 10.57, P = 0.000)] [Figure 3].
Figure 3: Forest plot for the KPS

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Nausea and vomiting

Ten studies provided the nausea and vomiting toxicity of the KLT combined chemotherapy and chemotherapy alone group. The heterogeneity test showed no statistical heterogeneity was found among the studies. Thus, the data was pooled by fixed effect model. And the pooled results indicated the KLT can decrease the risk of developing nausea and vomiting when patients received the systematic chemotherapy [RR = 0.53, 95% CI: 0.42-0.66, (Z = 5.53, P = 0.000), [Figure 4].
Figure 4: Forest plot for nausea and vomiting

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Publication bias

The publication bias was evaluated by Begg's funnel plot and Egger's line regression test. No publication bias was found in the pooled results of ORR and Gastrointestinal reaction (Pall > 0.05). But significant publication bias was found in the pooled results of KPS improvement [Figure 5].
Figure 5: Begg's test for evaluation of the publication bia

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 > Discussion Top


KLTanglaite injection, which had been confirmed with anti-tumor activity, is one of Chinese herb preparations that is developed and manufactured by Zhejiang Kanglaite Pharmaceutical Co., Ltd in China. [39] It is mainly used for the treatment of several types of tumors such as NSCLCno-small cell lung cancer, liver cancer, gastric cancer and etc., KLT is a unique botanically sourced molecular targeted agent prepared as a micro-emulsion for intravenous use. It is manufactured by the state of art technology with active substance extracted from a natural herbal plant semen coicis. Clinical trials demonstrated that KLT has several advantages in treatment of carcinomas. Firstly, KLT can killing cancer cells directly and effectively while remarkably improving patient immune function; Secondly, synergistic in increasing efficacy and reducing toxicity when combined with chemotherapy regimens or radiation therapy; Thirdly, providing high energy nutrition to treat cachexia; fourthly, controlling cancerous pain markedly; Fifthly, improving patients' quality of life and notably prolonging survival.

In this study, we include 34 trials comparing Kanglaite (KLD) injection combined with systematic chemotherapy versus chemotherapy alone in the treatment of NSCLC. Of the recruited 34 trails, the most common use chemotherapy regimens were NP, GP, EP and MVP. And the chemotherapy duration range from 10 days to 6 weeks. The pooled results showed that KLT injection combined with systematic chemotherapy can significant increase the objective response rate (ORR) [RR = 1.35, 95% CI: 1.23--1.48, (Z = 6.43, P = 0.000)], the quality of patients' life (KPS improvement) [RR = 2.04, 95% CI: 1.79-2.33, (Z = 10.57, P = 0.000)] and decrease the risk ratio of gastrointestinal reaction [RR = 0.53, 95% CI: 0.42-0.66, (Z = 5.53, P = 0.000)] compared with chemotherapy alone. The pooled data indicated that KLT injection combined with chemotherapy can improve the short-term efficacy, performance status and decrease the risk of gastrointestinal reaction compared with systematic chemotherapy alone.

Although the pooled results demonstrated good clinical efficacy for KLD injection assistant treatment NSCLC in this meta-analysis, there still several limitation for this study. Firstly, in the procedure of relevant articles searching and inclusion, we found all the trails are come from Chinese mainland; Secondly, the quality of the included 34 trials are relative low according to the quality evaluation system provided by Cochrane hand book; Thirdly, significant heterogeneity for the pooled results of KPS improvement was found. Fourthly, there was obviously publication bias in the aspect of KPS improvement.

In conclusion, the pooled data showed that KLT injection combined with chemotherapy can improve the short-term efficacy, performance status and decrease the risk of gastrointestinal reaction compared with systematic chemotherapy alone. But considering the limitations, the conclusion should be interpreted with caution.

 
 > References Top

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