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  Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 7  |  Page : 110-112
 

Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer: A meta-analysis based on Chinese patients


Department of Oncology, Quzhou People's Hospital, Quzhou 324000, Zhejiang Province, China

Date of Web Publication27-Mar-2015

Correspondence Address:
Y Zou
Department of Oncology, Quzhou People's Hospital, Quzhou 324000, Zhejiang Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.154100

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 » Abstract 

Background: Colorectal carcinoma is one of most diagnosed solid malignant carcinoma. The chemotherapy combined with target drugs in the treatment of advanced colorectal cancer in not conclusive. Methods: The clinical studies reporting the activity and adverse events between chemotherapy alone versus chemotherapy combined with anti-epidermal growth factor receptor drugs were screened in the databases of Medline, the Cochrane Library, Wanfang and CNKI and included in this meta-analysis. The risk ratio (RR) and its 95% confidence interval (CI) for treatment response and adverse events were pooled by random or fixed effect model. Results: A total of 10 clinical studies reporting chemotherapy combined with the target in the treatment of advanced colorectal cancer were included in this study. The pooled RR was 3.26 (95% CI: 1.74-6.11, P < 0.05), 1.49 (95% CI: 1.23-1.80) and 1.65 (95% CI: 1.37-1.98) for complete response (CR), partial response and objective response rate, respectively. For nausea and vomiting events, the RR was 1.62 (95% CI: 1.33-1.97, P < 0.05) indicating higher incidence of nausea and vomiting was observed in the combined group compared with chemotherapy alone. However, the diarrhea (RR = 1.10, 95% CI: 0.86-1.42, P > 0.05), liver function damage (RR = 1.03, 95% CI: 0.74-1.42), myelosuppression (RR = 1.04, 95% CI: 0.83-1.31) and neurotoxicity (RR = 1.12, 95% CI: 0.93-1.35) were not different between the two groups. Conclusion: For Chinese patients with advanced colorectal cancer, chemotherapy combined with target drug can improve the response rate, but also increase the risk of nausea and vomiting.


Keywords: Advance colorectal cancer, bevacizumab, cetuximab, chemotherapy, meta-analysis


How to cite this article:
Zheng Q H, Wu X L, Che X L, Weng M L, Chen J X, Zou Y. Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer: A meta-analysis based on Chinese patients. Indian J Cancer 2014;51, Suppl S3:110-2

How to cite this URL:
Zheng Q H, Wu X L, Che X L, Weng M L, Chen J X, Zou Y. Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer: A meta-analysis based on Chinese patients. Indian J Cancer [serial online] 2014 [cited 2020 Aug 12];51, Suppl S3:110-2. Available from: http://www.indianjcancer.com/text.asp?2014/51/7/110/154100



 » Introduction Top


Colorectal cancer is the third most common cancers and also the second leading cause of cancer-related death in the USA. [1] In China, colorectal cancer was believed as the 5 th cause of cancer-related death. [2] Surgery followed by adjuvant chemotherapy was the standard treatment for nonmetastatic colorectal cancer. However, the response rate of standard chemotherapy range from 10% to 30% for advanced colorectal cancer and reached the bottleneck. [3],[4] Molecular target therapy for colorectal cancer has brought notable clinical improvement across multiple lines of therapy over the past years. [5] But, the results from Chinese patients were seldom and not conclusive. We performed this meta-analysis using the published data on Chinese patients to explicated the activity and adverse effects for combination target drug and chemotherapy in the treatment of advanced colorectal cancer.


 » Methods Top


Search strategy

Medline, the Cochrane Library, Wanfang and CNKI were searched from by using the keywords of "cetuximab" or "Erbitux," "bevacizumab" or "Avastin," "colorectal cancer," "colorectal neoplasm," "colorectal carcinoma." The clinical studies reporting the activity and adverse events between chemotherapy alone versus chemotherapy combined with target drugs were screened and included in this meta-analysis. The studies included in this meta-analysis were restricted to (1) Clinical controlled studies; (2) advanced colorectal carcinoma patients with pathology confirmation; (3) chemotherapy alone versus chemotherapy combed cetuximab or bevacizumab; (4) Chinese patients; (5) published in English or Chinese.

Data extraction

For each of the included 10 articles, we collected general information regarding authors, year of publication, number of patients included in each study, chemotherapy regimens, target drugs and performance status by two reviews independently. The number of case for complete response (CR), partial response (PR) and adverse events (nausea and vomiting, diarrhea, liver function damage, myelosuppression, and neurotoxicity) were also extracted and cross checked by QZ, and XW independently. And minor discrepancies were resolved by the authors' discussion or consulting to the corresponding author JC.

Statistical method

The risk ratio (RR) (hazard ratio) for CR, PR objective response rate (ORR) and adverse events were treated as dichotomous variables and expressed by their 95% confidence interval (CI). The statistical heterogeneity among the studies was first assessed by I2 test. I2 of 25-50%, 50-75%, or >75% were considered to have low, moderate, or high heterogeneity, respectively. [6] If higher heterogeneity was found, the random effect model (DerSimonian-Laird method) was employed to calculated the RR and its 95% CI; And if low and moderate heterogeneity was found, the RR was pooled by fixed effect model (Mantel-Haenszel method). A P < 0.05 is deemed as statistically significant. All analyses are performed by STATA 12.0 (Stata Corporation, College Station, TX, USA).


 » Results Top


Description of included trials

Finally, the search strategy generated 10 studies, all of which were clinical controlled studies. All of the included patients were Chinese. 6 studies compared the chemotherapy with chemotherapy combined cetuximab and other 4 studies compared the chemotherapy with chemotherapy combined with bevacizumab. The ORR range from 12.5% to 56.0% with and median of 33.1% in chemotherapy alone group and range from 35.3% to 85.0%with a median of 49.2% in the combined treatment modality. The baseline of the included studies was showed in [Table 1].
Table 1: Baseline of include patients

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Overall response

The statistical heterogeneity analysis indicated no significant heterogeneity among the included studies for pooling the CR or PR (I2 = 0.00, P > 0.05). The fixed effect model was employed for pooling the CR, PR and ORR. The pooled RR was 3.26 (95% CI: 1.74-6.11, P < 0.05), 1.49 (95% CI: 1.23-1.80) and 1.65 (95% CI: 1.37-1.98) for CR, PR and ORR respectively. The pooled results indicated that the CR, PR and ORR were significant increase in the chemotherapy combined with target drug treatment strategy [Figure 1].
Figure 1: Forest plot for complete response, partial response and objective response rate

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Adverse events

Nine studies reported the nausea and vomiting adverse events in the chemotherapy and chemotherapy combined treatment group. The RR was pooled by fixed effect model for no statistical heterogeneity. The pooled results showed that the nausea and vomiting events was higher in the combined group compared with chemotherapy alone group with RR of 1.62 (95% CI: 1.33-1.97, P < 0.05). But, the diarrhea (RR = 1.10, 95% CI: 0.86-1.42, P > 0.05), liver function damage (RR = 1.03, 95% CI: 0.74-1.42), myelosuppression (RR = 1.04, 95% CI: 0.83-1.31) and neurotoxicity (RR = 1.12, 95% CI: 0.93-1.35) were not different between the two groups [Figure 2].
Figure 2: The forest plot of adverse events between the two groups

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Publication bias

We performed the Begg's funnel plots and egger's regression test for ORR and adverse events to evaluate the presence of any publication bias. No evidence of obvious publication bias was found according to the funnel plots [Figure 3] or egger's regression test in ORR (t = 1.86, P = 0.08), adverse events (t = 1.17, P = 0.09).
Figure 3: The funnel plot for evaluation of the publication bias: (a) For objective response rate; (b) for adverse events

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 » Discussion Top


In this meta-analysis, 10 clinical studies reporting chemotherapy combined with target drugs in the treatment of advanced colorectal cancer were included in this study. The pooled RR was 3.26 (95% CI: 1.74-6.11, P < 0.05), 1.49 (95% CI: 1.23-1.80) and 1.65 (95% CI: 1.37-1.98) for CR, PR and ORR respectively. Not only the CR but also the PR and ORR were also improved by adding the target drugs of cetuximab or bevacizumab. These results indicated that patients received the chemotherapy and cetuximab or bevacizumab had more opportunity of CR, PR and objective response. Target drugs plus cetuximab or bevacizumab can improve the short-term efficacy for Chinese advanced colorectal patients. But without enough data of long-term data of each individual study, the combined long-term results such as overall survival and progression survival were not pooled. As we all known, the most important primary end point for a prospective randomized controlled trials were progression free survival and overall survival. Lacking enough data for pooling these primary results of progression survival and overall survival mad this meta-analysis weakness.

For nausea and vomiting events, the RR was 1.62 (95% CI: 1.33-1.97, P < 0.05) indicating higher incidence of nausea and vomiting was observed in the combined group compared to chemotherapy alone. But the diarrhea (RR = 1.10, 95% CI: 0.86-1.42, P > 0.05), liver function damage (RR = 1.03, 95% CI: 0.74-1.42), myelosuppression (RR = 1.04, 95% CI: 0.83-1.31) and neurotoxicity (RR = 1.12, 95% CI: 0.93-1.35) were not different between the two groups. We can find from this meta-analysis, the adverse events risk of nausea and vomiting was significant increased by adding the target drug drugs of cetuximab or bevacizumab. But, the other side-effects such as diarrhea, liver function damage, myelosuppression and neurotoxicity were not increase by adding anti-epidermal growth factor receptor drugs. And the risk of developing nausea and vomiting was slightly increased by 62% compared to chemotherapy alone. We believe this increased adverse events can be compromised by its improvements for response rate.


 » Conclusion Top


For Chinese patients with advanced colorectal cancer, chemotherapy combined with target drug can improve the response rate with a slightly increased risk of nausea and vomiting.[16]

 
 » References Top

1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 1
    
2.
Zhang SW, Lei ZL, Li GL, Zou XN, Chen WQ, Zhao P. A report of cancer incidence and mortality from 34 cancer registries in China, 2005. China Cancer 2009;18:973-9.  Back to cited text no. 2
    
3.
Brezden-Masley C, Polenz C. Current practices and challenges of adjuvant chemotherapy in patients with colorectal cancer. Surg Oncol Clin N Am 2014;23:49-58.  Back to cited text no. 3
    
4.
Berry SR, Cosby R, Asmis T, Chan K, Hammad N, Krzyzanowska MK, et al. Continuous versus intermittent chemotherapy strategies in metastatic colorectal cancer: A systematic review and meta-analysis. Ann Oncol 2014;23:1-12.  Back to cited text no. 4
    
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Cheng L, Ren W, Xie L, Li M, Liu J, Hu J, et al. Anti-EGFR MoAb treatment in colorectal cancer: Limitations, controversies, and contradictories. Cancer Chemother Pharmacol 2014;74:1-13.  Back to cited text no. 5
    
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Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.  Back to cited text no. 6
    
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Chen ZG, Zhong M. Effect of cetuximab combined with FUFOX regimen in treatment of patients with advanced colorectal cancer. Mod J Integr Tradit Chin West Med 2011;20:2993-5, 3052.  Back to cited text no. 7
    
8.
Hu F, Wang Q, Wang XH, Liu YG. Cetuximab combjned with chemotherapy in the treatment of Advance colorectal cancer. Inn Mong Med J 2010;42:658-60.  Back to cited text no. 8
    
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Li HM, Lu HJ, Feng R, Zhang J, Chi YQ. Bevacizumab in the treatment of metastasis colorectal cancer with 20 case. Shandong Med J 2007;47:54-5.  Back to cited text no. 9
    
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Lin L, Xu JM, Wang Y, Ge FJ, Liu LJ, Zhao CH, et al. Evaluation of bevacizumab combined with irinotecan-based regimen as the first-line treatment for patients with metastatic colorectal cancer. Zhonghua Zhong Liu Za Zhi 2010;32:786-90.  Back to cited text no. 10
    
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Liu JK, Zheng YB, Tong SL, Cao FY, He XB, Gan HF. Clinical research of bevacizumab plus chemotherapy for advanced metastatic colorectal cancer. Chin J Gastroenterol Hepatol 2011;20:900-3.  Back to cited text no. 11
    
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Mao H, Shi Y, Wang ZK, Wu ZY, Dai GH. The short-term therapeutic effect of cetuximab plus FOLFIRI versus FOLFIRI alone in the treatment of patients with metastatic colorectal cancer. Prog Mod Biomed 2012;12:1893-6.  Back to cited text no. 12
    
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Wang XH, Huang Y. Comparison the effects of single used FOLFIRI and its combination with cetuximab in the treatment colorectal cancer. Chin J Clin Pharmacol 2011;27:972-5.  Back to cited text no. 13
    
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Wei Y, Zhou X, Zhou H, Wang LY, Li C, Zhao X, et al. Cetuximab combined with FOLFOX4 chemotherapy regimen in the treatment of advacnecd colorectal cancer. Contemp Med 2010;16:6-8.  Back to cited text no. 14
    
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Xie JM, Xie YL, Chen JZ, Li LB, Liao WJ. Effect of bevacizumab combined with FOLFOX4 on advanced colorectal cancer. China Trop Med 2010;10:1393-4.  Back to cited text no. 15
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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