Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: a systematic review

22nd Monday, 2014  |   Lung Cancer  |  no comments

Chen S, Flower A, Ritchie A, Liu J, Molassiotis A, Yu H, Lewith G


CRD summary
This review assessed the efficacy and safety of oral Chinese herbal medicine as adjuvant treatment during chemotherapy for non-small cell lung cancer; it found that Chinese herbal medicine may improve quality of life. The authors noted that further, more rigorous research is needed. These cautious conclusions were appropriate, given the limitations of the review and weaknesses in the underlying trials.
Authors’ objectives

To assess the efficacy and safety of oral Chinese herbal medicine as an adjuvant treatment during chemotherapy for non-small cell lung cancer.

MEDLINE, EMBASE, AMED, CINAHL, National Library of Guidelines (NHS Evidence NHL), Cochrane Central Register of Controlled Trials (CENTRAL) and four Chinese language databases were searched to June 2008. Search terms were reported. Bibliographies of included studies and reviews were screened for additional articles.

Study selection
Randomized controlled trials (RCTs) that compared adjuvant Chinese herbal medicine with inactive placebo, different adjuvant Chinese herbal medicine regimes, or adjuvant Chinese herbal medicine versus conventional biomedical treatment, in patients receiving treatment for non-small cell lung cancer, were eligible for inclusion. Trials using intravenous Chinese herbal medicine, interventions such as radiotherapy, acupuncture, or a complicated sequence of treatment (such as various vitamin supplementations) were excluded.

Primary outcome measures were response rate and survival rate. Secondary outcomes were side effects from chemotherapy, quality of life measures, adverse events associated with Chinese herbal medicine, and compliance to chemotherapy regimes.

All the trials took place in hospitals in China among in-patients. All but three of the included trials were performed exclusively in patients with stages III and IV non-small cell lung cancer. Types of Chinese herbal medicine and chemotherapy regimes varied (details reported). One trial was included that compared Chinese herbal medicine alone with chemotherapy alone (not Chinese herbal medicine as an adjuvant treatment, as specified by the inclusion criteria). Trial duration appeared to range from four weeks to six months.

Assessment of study quality
The authors did not apply a validated quality assessment tool, but recorded a number of aspects of methodological quality including: reporting of clear inclusion and exclusion criteria and appropriate participant characteristics; comparable treatment and control groups at baseline; acceptable method of randomization (no more than a 10% variation between the number of participants in the treatment and control group); allocation concealment; the number of randomized participants excluded or lost to follow-up; use of intention to treat analysis; and blinding of outcome assessors. Details of the duration, timing and the location of the trial, confirmation of the care programmes, and the types of Chinese herbal medicine and placebos used along with their methods of administration, also appeared to form part of the quality assessment.

The authors stated that if all quality criteria were met, the trial was categorised as low risk of bias (A); if one or more criteria were only partly met, the trial was at moderate risk of bias (B); if one or more criteria not met, the trial was at high risk of bias (C).

Methods of synthesis
Pooled estimates of relative risk (RR), with 95% confidence intervals (CIs), were calculated for any outcome measure reported by two or more trials. Where significant heterogeneity was identified (I2 over 50%), a random-effects model was used, otherwise a fixed-effect model was applied.

Results of the review
Fifteen trials were included in the review (n=862 patients). All trials were of poor quality (classified as at a high risk of bias).

The comparisons assessed were: Chinese herbal medicine plus chemotherapy versus chemotherapy (nine trials; n=558 patients); Chinese herbal medicine plus chemotherapy versus chemotherapy versus Chinese herbal medicine (three trials; n=242 patients); Chinese herbal medicine versus another Chinese herbal medicine (one trial; n=51 patients); Chinese herbal medicine plus chemotherapy versus other Chinese herbal medicine plus chemotherapy (one trial; n=40 patients); and Chinese herbal medicine versus chemotherapy (one trial; n=112 patients).

Chinese herbal medicine plus chemotherapy versus chemotherapy alone: Adjuvant therapy with Chinese herbal medicine showed no significant improvements in survival compared with chemotherapy alone for studies of patients at all stages of non-small cell lung cancer. Adjuvant Chinese herbal medicine was associated with an improvement in quality of life (as measured on the Karnofsky Performance Scale, KPS) compared with chemotherapy alone (RR 1.83, 95% CI 1.42 to 2.36; nine trials) and with increased weight stability (RR 1.40, 95% CI 1.11 to 1.76; two trials). Adjuvant Chinese herbal medicine was also associated with a reduction in the risk of anaemia (RR 0.42, 95% CI 0.23 to 0.77; two trials) and a reduction in the risk of neutropenia (RR 0.34, 95% CI 0.20 to 0.57; five trials). Results were similar for trials that included only non-small cell lung cancer stage III and IV patients. No other outcome measures showed significant differences between Chinese herbal medicine and chemotherapy and chemotherapy alone.

Chinese herbal medicine alone versus chemotherapy alone: Chinese herbal medicine alone was associated with an improvement in quality of life (KPS scores) compared with chemotherapy alone (RR 2.71, 95% CI 1.69 to 4.33; four trials) for all stages of non-small cell lung cancer; it was also associated with increased weight stability (RR 1.46, 95% CI 1.17 to 1.82; two trials) for all stages of non-small cell lung cancer. In addition, one trial showed an increase in the one year survival rate, (RR 2.16, 95% CI 1.35 to 3.46; n=103 patients) for Chinese herbal medicine alone compared with chemotherapy alone, and one trial showed a decrease in the risk of anaemia (RR 0.15, 95% CI 0.04 to 0.61; n=67 patients). No other outcome measures showed significant differences between Chinese herbal medicine alone and chemotherapy alone.

No measures of statistical heterogeneity were reported.

Authors’ conclusions
It was possible that oral Chinese herbal medicine used in conjunction with chemotherapy may improve quality of life in non-small cell lung cancer. This needs to be examined further with more rigorous methodology.

CRD commentary
The review applied well defined inclusion criteria to a clearly stated research question. The inclusion of one trial which compared Chinese herbal medicine alone with chemotherapy alone and had no Chinese herbal medicine adjuvant therapy group, appeared to be outside the inclusion criteria defined. A range of sources were searched for relevant trials. Measures to minimise error and/or bias were applied to the study selection process, but it was unclear whether similar measures were used throughout the review.

Although a validated quality assessment tool was not used, the authors reported relevant aspects of the methodological quality and highlighted the poor quality of all included trials. The meta-analytic methods applied were broadly appropriate, although interpretation of the overall findings was hindered by the lack of results for individual trials. In addition, it was unclear which meta-analytic model was actually used (fixed-effect or random-effects model) as no statistical heterogeneity data were reported.

The authors’ cautious conclusions were appropriate, given the limitations of the review and the weakness of the underlying trials.

Implications of the review for practice and research

Bibliographic details
Chen S, Flower A, Ritchie A, Liu J, Molassiotis A, Yu H, Lewith G. Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: a systematic review Lung Cancer 2010; 68(2): 137-145

Mind matters in cancer survival

18th Thursday, 2014  |   Cancer  |  no comments

Spiegel D. Psychooncology. 2012 Jun;21(6):588-93. doi: 10.1002/pon.3067. Epub 2012 Mar 21.


OBJECTIVE: The very name “psycho-oncology” implies interaction between brain and body. One of the most intriguing scientific questions for the field is whether or not living better may also mean living longer.

METHODS: Randomized intervention trials examining this question will be reviewed.

RESULTS: The majority show a survival advantage for patients randomized to psychologically effective interventions for individuals with a variety of cancers, including breast, melanoma, gastrointestinal, lymphoma, and lung cancers. Importantly, for breast and other cancers, when aggressive anti-tumor treatments are less effective, supportive approaches appear to become more useful. This is highlighted by a recent randomized clinical trial of palliative care for non-small cell lung cancer patients.There is growing evidence that disruption of circadian rhythms, including rest-activity patterns and hypothalamic-pituitary-adrenal (HPA) axis function, affects cancer risk and progression. Women with metastatic breast cancer have flatter diurnal cortisol patterns than normal, and the degree of loss of daily variation in cortisol predicts earlier mortality. Mechanisms by which abnormal cortisol patterns affect metabolism, gene expression, and immune function are reviewed. The HPA hyperactivity associated with depression can produce elevated levels of cytokines that affect the brain. Tumor cells can, in turn, co-opt certain mediators of inflammation such as NFkB, interleukin-6, and angiogenic factors to promote metastasis. Also, exposure to elevated levels of norepinephrine triggers release of vascular endothelial growth factor, which facilitates tumor growth.

CONCLUSIONS: Therefore, the stress of advancing cancer and management of it is associated with endocrine, immune, and autonomic dysfunction that has consequences for host resistance to cancer progression.

Daniel Weber with the International Consortium of Chinese Medicine and Cancer at the National Cancer Institute (NIH) in Bethesda Nov. 3 2014

19th Wednesday, 2014  |   Slider  |  no comments

Daniel Weber with the International Consortium of Chinese Medicine and Cancer

at the National Cancer Institute (NIH) in Bethesda Nov. 3 2014 continue reading

Did Cancer Evolve to Protect Us?

9th Thursday, 2014  |   Cancer  |  no comments

A physics-based, “atavistic” model posits that cancer is a “safe mode” for stressed cells and suggests that oxygen and immunotherapy are the best ways to beat the disease

Oct 2, 2014 By Zeeya Merali. Scientific American

A new theory declares cancer is the re-expression of an ancient “preprogrammed” trait that has been lying dormant.

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Could cancer be our cells’ way of running in “safe mode,” like a damaged computer operating system trying to preserve itself, when faced with an external threat? That’s the conclusion reached by cosmologist Paul Davies at Arizona State University in Tempe (A.S.U.) and his colleagues, who have devised a controversial new theory for cancer’s origins, based on its evolutionary roots. If correct, their model suggests that a number of alternative therapies, including treatment with oxygen and infection with viral or bacterial agents, could be particularly effective.

At first glance, Davies, who is trained in physics rather than biomedical science, seems an unlikely soldier in the “war on cancer.” But about seven years ago he was invited to set up a new institute at A.S.U.—one of 12 funded by the National Cancer Institute—to bring together physical scientists and oncologists to find a new perspective on the disease. “We were asked to rethink cancer from the bottom up,” Davies says.

Davies teamed up with Charley Lineweaver, an astrobiologist at The Australian National University in Canberra, and Mark Vincent, an oncologist at the London Health Sciences Center in Ontario. Together they have come up with an “atavistic” model positing cancer is the reexpression of an ancient “preprogrammed” trait that has been lying dormant. In a new paper, which appeared in BioEssays in September, they argue that because cancer appears in many animals and plants, as well as humans, then it must have evolved hundreds of millions of years ago when we shared a common single-celled ancestor. At that time, cells benefited from immortality, or the ability to proliferate unchecked, as cancer does. When complex multicellular organisms developed, however, “immortality was outsourced to the eggs and sperm,” Davies says, and somatic cells (those not involved in reproduction) no longer needed this function.

The team’s hypothesis is that when faced with an environmental threat to the health of a cell—radiation, say, or a lifestyle factor—cells can revert to a “preprogrammed safe mode.” In so doing, the cells jettison higher functionality and switch their dormant ability to proliferate back on in a misguided attempt to survive. “Cancer is a fail-safe,” Davies remarks. “Once the subroutine is triggered, it implements its program ruthlessly.”

Speaking at a medical engineering conference held at Imperial College London, on September 11, Davies outlined a set of therapies for cancer based on this atavistic model. Rather than simply attacking cancer’s ability to reproduce, or “cancer’s strength,” as Davies terms it, the model exposes “cancer’s Achilles’ heel.” For instance, if the theory is correct, then cancer evolved at a time when Earth’s environment was more acidic and contained less oxygen. So the team predicts that treating patients with high levels of oxygen and reducing sugar in their diet, to lower acidity, will strain the cancer and cause tumors to shrink.

The effects of oxygen level on cancer have been independently investigated for many years and appear to support Davies’s ideas, says Costantino Balestra, a physiologist at Paul Henri Spaak School and the Free University of Brussels, both in Belgium. In unpublished work that has been submitted for peer review, for instance, Balestra and his colleagues have recently demonstrated that slightly elevated oxygen levels can begin to induce leukemia cell death without harming healthy cells. “It almost looks too easy,” Balestra says. “Our preliminary results seem to show that supplying a little extra oxygen for one or two hours a day, in combination with other traditional cancer therapies, would benefit patients without any harsh side effects.” Balestra emphasizes, however, that this work was not carried out to test Davies’s hypothesis and cannot be taken as proof that the atavistic model is correct.

Davies and his colleagues also advocate immunotherapy—specifically, selectively infecting patients with bacterial or viral agents. Medical researchers are already investigating the promising effects of such an approach for artificially boosting patients’ immune systems to aid in their recovery. Immunotherapy has already performed well in treating melanomas, for instance, and its effects on other cancers are being studied. According to the atavistic model, however, in addition to invigorating the immune system, cancer cells should also be more vulnerable than healthy cells to being killed by infectious agents because they lose higher protective functionality when they “reboot into safe mode,” Davies says. Recent studies injecting clostridium spores in rats, dogs and a human patient also appear to support this interpretation, he says.

Some scientists, such as David Gorski, a surgical oncologist at Wayne State University, remain skeptical. “The ‘predictions’ of atavism are nothing that scientists haven’t come to by other paths,” he says.

Davies and his colleagues have already begun a more direct test of their theory, in answer to such criticisms. “The key to our theory is looking at the ages of the genes responsible for cancer,” Davies explains. The atavistic model claims that with the onset of cancer, cells revert to a more primitive mode and more recently evolved functions are switched off. The team therefore predicts that as cancer progresses, more recently evolved genes should lose function, whereas ancient genes become active.

To check if this hypothesis is correct, Davies and his colleagues are currently cross-referencing data from the cancer genome atlas, which identifies the genes that are involved in cancer, with various databases that classify the genes that we have in common with other species. The latter data set enables biologists to trace back genes’ ages. Any correlation that exists between the gene age and cancer will be a boost to the atavistic model. “Combining the two data sets hasn’t been done before,” Davies says. “But it’s essentially a data-mining exercise that doesn’t take much money and it’s something we’re working on now.”

Brendon Coventry, a surgical oncologist and immunotherapist at the University of Adelaide in Australia, sees value in physicists working with oncologists to piece together existing medical evidence to try to understand cancer’s origins. “Enormous amounts of money and the brightest minds in biological and medical science have failed to make a big impact in the war on cancer, so maybe it’s time for a new paradigm,” Coventry says, adding: “A cosmologist can look at the cell as an ‘internal universe’ to be explored in a new way.”

Adjuvant phytotherapy in the treatment of cervical cancer: a systematic review and meta-analysis

7th Tuesday, 2014  |   Cancer, Cervical Cancer  |  no comments


Xu M, Deng PX, Qi C, Deng B, Zhao ZZ, Wong V, Ngan T, Kan V, Tian XY, Xu DY, Au D. Journal of Alternative and Complementary Medicine 2009; 15(12): 1347-1353

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.

Authors’ objectives
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.

Study selection
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.

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.

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.

Authors’ conclusions
Adjuvant phytotherapy may increase survival rate, tumour regression rate and decrease vesical complications in the clinical treatment of cervical cancer.

CRD commentary
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.

PubMedID: 19954338
DOI: 10.1089/acm.2009.0202
Date abstract record published 27/10/2010

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