|Adjuvant phytotherapy in the treatment of cervical cancer: a systematic review and meta-analysis
|Xu M, Deng PX, Qi C, Deng B, Zhao ZZ, Wong V, Ngan T, Kan V, Tian XY, Xu DY, Au D
This review compared conventional therapies versus adjuvant phytotherapy in treating patients with cervical cancer. The authors concluded that adjuvant phytotherapy may increase survival and tumour regression rates and decrease vesical complications, but that the results require verification. This cautious conclusion appears to reliably reflect limited evidence from the generally poor quality available trials.
To compare the efficacy and safety of conventional therapies with conventional therapies plus adjuvant phytotherapy in the treatment of cervical cancer.
Forty-three electronic databases were searched, including MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, several Chinese data sources (listed in the paper) and other databases (e.g. WorldCat, MetaPress, SpringerLink, Oxford Journals Online, Blackwell Synergy, ScienceDirect, and ProQuest). Search terms were reported. Sources of unpublished material, such as the China Proceedings of Conference Databases and China Doctorate/Master Dissertations Full Text Databases, were also searched. Reference lists of retrieved papers were scanned. Handsearching of the latest articles in selected University libraries (details given) was carried out to June 2008. There were no language restrictions.
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the effects and safety of conventional therapies plus phytotherapy with conventional therapies alone; or those comparing phytotherapy, or phytotherapy plus Western medication with Western medication alone, in women with histopathologically confirmed cervical cancer, were eligible for inclusion in the review. Patients receiving non-oral phytotherapy treatments were excluded.
Eligible outcomes were survival rate, tumour regression rate, and vesical or rectal complications.
Over half of included patients were classified with advanced stage cervical cancer (stage IIB and above); the majority of cases were squamous cell carcinoma. Intervention durations ranged from five days to 10 years. Just over half of the included trials measured survival rate and tumour regression rate; the remainder measured vesical or rectal complications. The most frequently used phytotherapeutic herbs amongst the included trials were reported; just under half of trials used Radix astragali.
Two independent reviewers selected the trials for inclusion.
Assessment of study quality
Trial quality was assessed using the Jadad criteria, covering randomisation, double-blinding, and drop-out rate. Trials were scored from 1 to 5, where trials scoring 1 and 2 were considered to be low quality, and trials scoring 3 to 5 were considered high quality.
The authors did not state how many reviewers carried out the validity assessment.
Data were extracted on numbers and percentages of patients for each outcome, to enable the calculation of odds ratios (OR) and 95% confidence intervals (CI). Authors were contacted for missing information, where necessary.
Data were extracted by one reviewer and confirmed by a second reviewer.
Methods of synthesis
Odds ratios and 95% confidence intervals were pooled in a fixed-effect meta-analysis. Statistical heterogeneity was assessed using the Q-test (Mantel Haenszel X2 test). Sources of heterogeneity were explored in subgroup analysis.
Results of the review
Eighteen RCTs (n=1,657 patients) were included in the review. Two trials were considered to be high quality (with Jadad scores of 3); the remainder were low quality (Jadad scores of 0 and 1). Two trials that compared phytotherapy plus Western medications with Western medications alone appeared to be part of the same study, raising the possibility of duplicate analysis of patients.
Efficacy assessment: Pooled results showed an increased survival rate at one-year for patients receiving conventional therapies plus phytotherapy (94.5%), compared with those receiving conventional therapies alone (83.1%); odds ratio 4.16 (95% CI 1.97 to 8.78; four trials; n=427 patients). Data from the trials indicated that survival rates were higher for two-year, three-year and 10-year survival, but that there was no significant difference in five-year survival. Tumour regression rate was also significantly higher in patients receiving conventional therapies plus phytotherapy (87.1%) compared with conventional therapy alone (70.2%); odds ratio 5.12 (95% CI 2.28 to 11.50; five trials; n=281 patients). There was no statistically significant heterogeneity in either analysis.
Safety assessment: Pooled results showed a significantly diminished vesical complication rate in patients receiving phytotherapy or phytotherapy plus Western medication (94.2%) compared with Western medication alone (81.9%); odds ratio 3.61 (95% CI 1.92 to 6.79; four trials; n=475 patients). There was no statistically significant heterogeneity. The effect on rectal complications (even after sub-group analysis to minimise heterogeneity) showed that phytotherapy or phytotherapy plus Western medication was generally favourable compared with Western medication alone, but the results were not statistically significant and significant heterogeneity was found.
Adjuvant phytotherapy may increase survival rate, tumour regression rate and decrease vesical complications in the clinical treatment of cervical cancer.
The review addressed a clear question, and this was supported by detailed and potentially reproducible inclusion criteria. The search strategy included an extensive list of data sources, and efforts were made to minimise language and publication biases. The review process was carried out with some attempts to minimise error and bias in the selection of studies and data extraction. The process was unreported for validity assessment.
An appropriate validity assessment tool was applied to the trials, revealing that the evidence was generally of poor quality. Trial details were provided, and this revealed the possibility of double-counting of patients. The chosen method of synthesis appeared to be appropriate in most cases; sub-group analysis was carried out to explore the effect of heterogeneity.
The authors' cautious conclusion appears to reliably reflect limited evidence from generally poor quality trials.
Implications of the review for practice and research
Practice: The authors stated that adjuvant phytotherapy should be of value to improve the survival rate of patients, including those at the advance stages of cervical cancer.
Research: The authors stated that further large-scale, long-term RCTs are needed to verify the results of this review, and examine the effects of phytotherapy in treating cervical cancer, specifically in patients with vesical complications resulting from conventional therapies. Research should also focus on the commonly-used herbs identified in this review.
Hong Kong Baptist University, grant number FRG/07-08/I-37; Hospital Authority of Hong Kong, grant number HOC172-06.
Xu M, Deng PX, Qi C, Deng B, Zhao ZZ, Wong V, Ngan T, Kan V, Tian XY, Xu DY, Au D. Adjuvant phytotherapy in the treatment of cervical cancer: a systematic review and meta-analysis. Journal of Alternative and Complementary Medicine 2009; 15(12): 1347-1353
Subject indexing assigned by NLM
Antineoplastic Agents, Phytogenic /adverse effects /therapeutic use; Chemotherapy, Adjuvant; Clinical Trials as Topic; Female; Humans; Phytotherapy; Plant Extracts /therapeutic use; Remission Induction; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms /drug therapy /mortality
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.