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 Sources of unpublished material, such as the China Proceedings of Conference Databases and China Doctorate/Master Dissertations Full Text Databases, were also searched.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

Changes in Intestinal Permeability and Nutritional Status After Cytotoxic Therapy in Patients with Cancer

7th Tuesday, 2014  |   Cancer  |  no comments

Nutrition and Cancer. Volume 66, Issue 4, 2014 DOI: 10.1080/01635581.2014.894095


Damage to intestinal mucosa may impair nutritional status and increase the demand for nutrients involved in intestinal cell proliferation (retinol and folate). It is still unclear if cytotoxic therapy affects serum concentrations of these nutrients in patients with cancer and if this would be associated with disturbances of intestinal mucosa. Intestinal permeability, serum folate, and retinol and nutritional status of 22 patients with hematologic malignancies and 17 healthy volunteers [control group (CG)] were assessed before (T0) and after cytotoxic therapy (T1). Ingestion of lactulose and mannitol was used to assess intestinal permeability. Anthropometric, body composition, phase angle (PA), and biochemical analysis (albumin, retinol, and folate) were also performed. Lactulose/mannitol ratio (0.026 ± 0.014 vs. 0.052 ± 0.037) and lactulose excretion (0.27 ± 0.18% vs. 0.53 ± 0.6%) increased at T1. PA decreased (7.2 ± 1.9° vs. 6.2 ± 0.9°). Serum folate and albumin (20.7 ± 9.5 nmol/L, 37.7 ± 5.5 g/L) were lower than CG (39.2 ± 16.4 nmol/L, 42.9 ± 5.2 g/L) but did not change at T1 (17.5 ± 7.0 nmol/L, 35.9 ± 4.5 g/L). Serum retinol did not differ from CG and did not change at T1 (1.83 ± 0.30 ?mol/L vs. 1.69 ± 0.3 ?mol/L; CG: 1.86 ± 0.20 ?mol/L). Abnormal intestinal permeability, low serum folate levels, and its possible relationship with intestinal alterations, and reduced PA, may be associated with poor nutritional status in cancer patients.

Although cytotoxic therapy plays an important role in the management and cure of cancer, it may result in side effects that frequently affect the gastrointestinal tract (1). Mucositis is one possible side effect defined as a complex, dynamic, and interactive biopathological process involving the action of pro-inflammatory cytokines over the mucosa (2). Patients with hematologic malignancies treated with intensive chemotherapy and all those receiving myeloablative conditioning regimens prior to hematopoietic stem cell transplantation (HSCT) are often affected by this condition (3).

Mucositis may affect oral and intestinal mucosa. Inflammatory activation and damage within intestinal mucosa impairs its barrier function, essential for general homeostasis (2). Oral mucositis can be easily diagnosed by direct inspection, whereas assessment of intestinal mucosa damage still relies on anamnestic data (4). Because low platelet and white blood cell counts are also frequently observed in cancer patients as a result of chemotherapy, assessment of intestinal mucosa through small bowel biopsy and endoscopy could increase the risk of complications (5). Therefore, lactulose-mannitol intestinal permeability test is an alternative noninvasive method used for assessing intestinal barrier function in patients treated with cytotoxic drugs (4). Therefore, higher intestinal permeability may indicate impairment of barrier function, which in turn may be a consequence of intestinal mucositis (4).

Mucositis is also associated with a variety of clinical complications including pain, bleeding, dysphagia, diarrhea, and infections (1,6,7). This may lower food intake, which can negatively affect nutritional status (8). The nutritional status influences the prognosis of cancer patients (9). Although undernutrition is highly prevalent in patients with head, neck and gastrointestinal cancers (9), weight gain and obesity are also commonly observed in patients with hematologic malignancies (10). Chemotherapy, decreased physical activity, and increased total caloric intake may contribute to weight gain (11,12). Therefore, evaluation of body composition in cancer patients is of great importance. Phase angle (PA) from bioelectrical impedance analysis (BIA) is proposed as a useful prognostic marker in clinical conditions like cancer (13). In addition, low serum concentrations of retinol and folate are also commonly observed in cancer patients (14–17). Clinical studies have investigated the association between pretreatment folate levels and oral and gastrointestinal toxicity. Nevertheless, results are still controversial (18,19). These nutrients are essential for stem cell proliferation in the gut and bone marrow (20–22). Its deficiency may be associated with impairment of gut barrier function and may delay the recovery of gastrointestinal cells from mucositis.

It is well known that cancer itself and cytotoxic therapy usually negatively affect nutritional status and gastrointestinal mucosa. This, in turn, may alter intestinal permeability and serum concentration of nutrients such as folate and retinol. Investigation of the association between these conditions may indicate the importance of future therapies aimed at correcting abnormally increased intestinal permeability in the context of cancer-associated undernutrition. Therefore, the aim of this study was to assess intestinal permeability, body composition, serum folate, and retinol concentrations and the associations between these variables in cancer patients after cytotoxic therapy.

1. Keefe DM, Gibson RJ, and Hauer-Jensen M: Gastrointestinal mucositis. Semin Oncol Nurs 20, 38–47, 2004. [CrossRef], [PubMed]
2. Sonis ST: The pathobiology of mucositis. Nat Rev Cancer 4, 277–284, 2004. [CrossRef], [PubMed], [Web of Science ®]
3. Niscola P, Romani C, Cupelli L, Scaramucci L, Tendas A, : Mucositis in patients with hematologic malignancies: an overview. Haematologica 92, 222–231, 2007. [CrossRef], [PubMed], [Web of Science ®]
4. Melichar B, Dvorák J, Hyspler R, and Zadák Z: Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents. Chemotherapy 51, 336–338, 2005. [CrossRef], [PubMed], [Web of Science ®]
5. Tooley KL, Howarth GS, and Butler RN: Mucositis and non-invasive markers of small intestinal function. Cancer Biol Ther 8, 753–758, 2005. [CrossRef], [Web of Science ®]
6. Davila M and Bresalier RS: Gastrointestinal complications of oncologic therapy. Nat Clin Pract Gastroenterol Hepatol 5, 682–696, 2008. [CrossRef], [PubMed]
7. Volpato LE, Silva TC, Oliveira TM, Sakai VT, and Machado MA: Radiation therapy and chemotherapy-induced oral mucositis. Braz J Otorhinolaryngol 73, 562–568, 2007. [PubMed]
8. Tisdale MJ: Cancer cachexia. Curr Opin Gastroenterol 26, 146–151, 2010. [CrossRef], [PubMed], [Web of Science ®]
9. Pressoir M, Desné S, Berchery D, Rossignol G, Poiree B, : Prevalence, risk factors and clinical implications of malnutrition in French comprehensive cancer centers. Br J Cancer 102, 966–971, 2010. [CrossRef], [PubMed], [Web of Science ®]
10. Withycombe JS, Post-White JE, Meza JL, Hawks RG, Smith LM, : Weight patterns in children with higher risk ALL: a report from the Children’s Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer 53, 1249–1254, 2009. [CrossRef], [PubMed], [Web of Science ®]
11. Jansen H, Postma A, Stolk RP, and Kamps WA: Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity? Support Care Cancer 17, 103–106, 2009. [CrossRef], [PubMed], [Web of Science ®]
12. Demark-Wahnefried W, Peterson BL, Winer EP, Marks L, Aziz N, : Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 19, 2381–2389, 2001. [PubMed], [Web of Science ®]
13. Norman K, Stobäus N, Zocher D, Bosy-Westphal A, Szramek A, : Cutoff percentiles of bioelectrical phase angle predict functionality, quality of life, and mortality in patients with cancer. Amer J Clin Nutr 92, 612–619, 2010. [CrossRef], [PubMed], [Web of Science ®]
14. Lin CC and Yin MC: Vitamins deficiency and decreased anti-oxidative state in patients with liver cancer. Eur J Nutr 46, 293–299, 2007. [CrossRef], [PubMed], [Web of Science ®]
15. Tsao SM, Yin MC, and Liu WH: Oxidant stress and B vitamins status in patients with non-small cell lung cancer. Nutr Cancer 59, 8–13, 2007. [Taylor & Francis Online], [PubMed], [Web of Science ®]
16. Iversen PO, Ukrainchenko E, Afanasyev B, Hulbekkmo K, Choukah A, : Impaired nutritional status during intensive chemotherapy in Russian and Norwegian cohorts with acute myeloid leukemia. LeukLymphoma, 49, 1916–1924, 2008.
17. Shim E, Yeum KJ, Tang G, Ahn SH, Hwang J, : Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients. Nutr Cancer 64, 956–963, 2012. [Taylor & Francis Online], [PubMed], [Web of Science ®]
18. Sharma R, Rivory L, Beale P, Ong S, Horvath L, : A phase II study of fixed-dose capecitabine and assessment of predictors of toxicity in patients with advanced/metastatic colorectal cancer. Br J Cancer 94, 964–968, 2006. [CrossRef], [PubMed], [Web of Science ®]
19. Branda RF, Naud SJ, Brooks EM, Chen Z, and Muss H: Effect of vitamin B12, folate and dietary supplements on breast carcinoma chemotherapy-induced mucositis and neutropenia. Cancer 101, 1058–1064, 2004. [CrossRef], [PubMed], [Web of Science ®]
20. Ponziani FR, Cazzato IA, Danese S, Fagiuoli S, Gionchetti P, : Folate in gastrointestinal health and disease. Eur Rev Med Pharmacol Sci 16, 376–385, 2012. [PubMed], [Web of Science ®]
21. Koury MJ and Ponka P: New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr 24, 105–131, 2004. [CrossRef], [PubMed], [Web of Science ®]
22. Yousefi B and Azizzadeh F: The histopathalogical effects of retinoic acid on the tissues. Pak J Biol Sci 13, 927–936, 2010. [CrossRef], [PubMed]

Valuable Data to Demonstrate How Cancer Survivors will Seek Out Complementary Therapies

23rd Tuesday, 2014  |   Cancer  |  no comments

Costs of Complementary and Alternative Medicine for Cancer Survivors in the United States: Results from the 2012 National Health Interview Survey

Gabriella John, Dawn Hershman, Laura Falci, Wei-Yann Tsai, Heather Greenlee. The Journal of Alternative and Complementary Medicine. May 2014, 20(5): A4-A4.

Screen Shot 2014-09-23 at 11.46.53 am

Purpose: While it is known that a high percentage of cancer survivors use complementary and alternative medicine (CAM), little is known about the financial implications of such use. We sought to determine cancer survivors’ annual out-of-pocket spending on CAM.

Methods: Data from the Adult Alternative Medicine questionnaire of the 2012 National Health Interview Survey (NHIS) were used to estimate out-of-pocket CAM costs among individuals with a history of a cancer diagnosis. The analysis was limited to adults with a history of cancer, excluding non- melanoma skin cancers. Statistical methods were used to account for NHIS’s complex sampling methods. We performed a multivariate analysis to determine factors associated with the highest quartile of CAM spending.

Results: We identified a cohort of 3,102 cancer survivors, of which 78.1% reported having used at least one CAM modality over the past 12 months. We estimated that adult cancer survivors in the United States spent $9.0 billion in total on out-of- pocket CAM use in 2012. Over two thirds of this total was spent on the purchase of vitamins and minerals ($6.2 billion), over 15% ($1.4 billion) was spent on herbs and non-vitamin supple- ments, and over 5% ($0.5 billion) was spent on massage. Breast cancer survivors were estimated to be the highest spending group, totaling $1.6 billion in out-of-pocket CAM costs over the past 12 months. Among all users, median annual cost of CAM use was estimated at $140. Compared to those who did not report CAM use due to their cancer diagnosis, survivors who reported using any CAM for cancer have 4.6 times the odds of being a high spender (p = 0.0028).

Conclusion: The total 2012 out-of-pocket CAM costs for cancer survivors in the United States are estimated to be $9.0 billion— 7% of the estimated $125 billion for cancer survivors’ yearly health care costs.

Berberine Targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and Cytochrome-c/Caspase Signaling to Suppress Human Cancer Cell Growth.

16th Tuesday, 2014  |   Cancer  |  no comments

Screen Shot 2014-09-16 at 10.57.28 am Berberine is an isoquinoline alkaloid with a bright yellow color that is easily seen in most of the herb materials that contain any significant amount of this compound. Among Chinese herbs, the primary sources are phellodendron and coptis Berberine (BBR), an isoquinoline derivative alkaloid isolated from Chinese herbs, has a long history of uses for the treatment of multiple diseases, including cancers. However, the precise mechanisms of actions of BBR in human lung cancer cells remain unclear. In this study, we investigated the molecular mechanisms by which BBR inhibits cell growth in human non-small-cell lung cancer (NSCLC) cells. Treatment with BBR promoted cell morphology change, inhibited cell migration, proliferation and colony formation, and induced cell apoptosis. Further molecular mechanism study showed that BBR simultaneously targeted multiple cell signaling pathways to inhibit NSCLC cell growth. Treatment with BBR inhibited AP-2? and AP-2? expression and abrogated their binding on hTERT promoters, thereby inhibiting hTERT expression. Knockdown of AP-2? and AP-2? by siRNA considerably augmented the BBR-mediated inhibition of cell growth. BBR also suppressed the nuclear translocation of p50/p65 NF-?B proteins and their binding to COX-2 promoter, causing inhibition of COX-2. BBR also downregulated HIF-1? and VEGF expression and inhibited Akt and ERK phosphorylation. Knockdown of HIF-1? by siRNA considerably augmented the BBR-mediated inhibition of cell growth. Moreover, BBR treatment triggered cytochrome-c release from mitochondrial inter-membrane space into cytosol, promoted cleavage of caspase and PARP, and affected expression of BAX and Bcl-2, thereby activating apoptotic pathway. Taken together, these results demonstrated that BBR inhibited NSCLC cell growth by simultaneously targeting AP-2/hTERT, NF-?B/COX-2, HIF-1?/VEGF, PI3K/AKT, Raf/MEK/ERK and cytochrome-c/caspase signaling pathways. Our findings provide new insights into understanding the anticancer mechanisms of BBR in human lung cancer therapy. Source Fu L, Chen w, Guo W et al. PLoS One. 2013 Jul 15;8(7):e69240. doi: 10.1371/journal.pone.0069240.

Cancer Screening Rates Are Too High in Older Adults with Limited Life Expectancy

27th Wednesday, 2014  |   Cancer, Uncategorized  |  no comments

JAMA Intern Med 2014 Aug 18


Between 31% and 55% of patients at very high risk for dying within 9 years underwent recent cancer screenings.

Many health organizations recommend against routine cancer screening in patients with short life expectancies (generally , <10 years), but inappropriately high screening rates persist (NEJM JW Gen Med Mar 20 2014). Investigators assessed self-reported cancer screening in about 27,000 older adults (age, ≥65) who were queried periodically between 2000 and 2010. A validated instrument was used to calculate 9-year mortality risk for each participant, and participants were grouped from low (<25%) to very high (≥75%) risk.

Overall screening rates for prostate, breast, cervical, and colorectal cancer declined with increasing 9-year mortality risk, but recent screening occurred at relatively high rates (55%, 38%, 31%, and 41%, respectively) among patients with the highest 9-year mortality risk. Likewise, screening rates declined with age, yet 55% of older women (age, ≥75) underwent screening for breast cancer, and 31% of the oldest adults (age, ≥85) were screened for colorectal cancer. Among women with prior hysterectomies for benign indications (a group for whom Papanicolaou smear is not recommended), 34% of those at high 9-year mortality risk had Pap smears within the past 3 years. Patients who had more education, were married, had health insurance, or had sources of medical care were more likely to be screened.

Although no “right” rate of screening can be specified for all the categories of adults who were assessed, some screening rates are disturbingly high, especially in patients for whom screening absolutely is not recommended. One major barrier to discontinuing screening based on life expectancy or older age is the difficult conversation that starts when a clinician recommends no screening, and the patient responds, “What? Do you think I’m too old to be screened?”

Royce TJ et al. Cancer screening rates in
individuals with different life expectancies. JAMA Intern Med 2014 Aug 18; [e-pub ahead of print]. (

Page 6 of 138« First...«45678»102030...Last »