Complementary and alternative (unproven) therapies
Complementary and alternative (unproven) therapies
Complementary medicine is any intervention that is used in conjunction with standard western health practices.
Integrative medicine is an approach that combines standard western health interventions and evidence based complementary medicines.
For example: the use of a course of relaxation therapy in conjunction with standard radiotherapy or chemotherapy regime to reduce stress anxiety.
Alternative medicine is an intervention or product offered as an alternative treatment to standard western medical practices.
(Source: Clinical Oncological Society of Australia CAM Definitions http://www.cosa.org.au)
The use of complementary and alternative (or unproven) medicine (CAM) has continued to increase. In 2004 it was reported that 52.2% of the Australian population used CAM. In North America the reported prevalence of CAM usage in prostate cancer lies between 18 and 45%. It is important that clinicians know about their patient's current and proposed CAM use as some CAM therapies can interfere with other therapies. However, a survey of patients using both conventional and complementary therapies found that many patients do not inform their doctor of their CAM use because they were not asked and because they did not see it important for the doctor to know. To gain a comprehensive picture of CAM use and thus avoid possible adverse interactions it is important that all patients be carefully questioned as to their current or proposed usage of CAM agents in a supportive, understanding and non-judgmental way. Schofield et al provides recommendations and suggestions on how to discuss CAM usage. Their systematic review revealed that there is no level IV or higher evidence for communicating about CAM with cancer patients. As a result their recommendations are based on a systematic review of descriptive studies of, a review of generic communication skills and expert opinion.
|Health professionals should ask their patients about their use of CAM therapies in a supportive, understanding and non-judgmental way.||D|
While there have been numerous reports on the level of CAM usage in men with prostate cancer, there are limited studies on the factors motivating them to use it. One studyhypothesised that users of CAM did not assess conventional and non-conventional treatments in the same way as non-users. CAM users perceived CAM to be safer than conventional treatments and showed greater concern for side effects of conventional therapy such as impotence. Non-users of CAM questioned its validity, perceived conventional care as ’curing‘ cancer and were more accepting of possible side effects such as impotence and secondary cancers. They had more definite views on the benefits flowing from conventional medicine and trusted their doctors more fully.
A prospective study involving 111 men noted that those who used CAM were more uncertain about prostate cancer and its treatment than men who chose to follow the conventional therapy route. However it was noted that CAM users were less distressed than non-users after a year of treatment.
In general there are two large areas of therapy for advanced prostate cancer under the CAM umbrella:
- touch therapies (eg Reiki, massage, acupuncture and mind–body interventions)
- dietary interventions (eg dietary modifications, vitamin and herbal supplements).
There are no randomised controlled trials (RCTs) examining the benefit of touch therapies in prostate cancer and so these are not discussed further in this chapter.
A wide range of products has been offered for the treatment of prostate cancer. While there is an increasing number of RCTs investigating the use of dietary interventions for treating cancer, the general rigour of such trials is frequently deficient or of poor quality. This feature, however, is not limited to CAM studies. Quality of life was not measured formally in any of the studies found. The following summary describes the RCTs that met the criteria for inclusion in these guidelines.
Only four dietary interventions have been subjected to RCTs that were completed and were not part of a chemotherapy-centred regimen. (see also section 2.3 Effect of diet and lifestyle interventions on quality of life, p7) CAMs showing potential were high-dose vitamin D (calcitriol), lycopene, ellagic acid, and the dietary supplement verum. Lycopene is a carotenoid and is claimed to be a quencher of free radicals and an immunomodulator. Ellagic acid, a polyphenol extracted from Punica Granatum (pomegranate) seeds may have pro-apoptotic and anti-oxidant properties. Verum is a dietary supplement that contains selenium, carotenoids and other putative prostate cancer inhibitors.
The role of vitamin D in treating cancer is not fully understood. It may block cancer cell proliferation or improve immune system function, however, further research is needed to clarify this association. Folinic acid forms part of some chemotherapy regimens and therefore is not included under CAM.
Another trial was planned to evaluate the efficiency of PC-SPECS, a herbal conglomerate, with that of diethylstilbestrol (DES) in a crossover study in patients with androgen-independent prostate cancer. This study was discontinued because the researchers found traces of DES in four samples of PCSPECS. Further studies by the California Department of Health found contamination with warfarin, alprazolam and DES. These observations highlight the need for investigators to ensure the purity of herbal cocktails they are using.
In a small, low powered study, Ansari et al compared lycopene with orchidectomy against orchidectomy alone among 54 patients with advanced prostate cancer. Patients in the lycopene and orchidectomy arm had a statistically significant increased survival as compared with the group who had orchidectomy alone (p<0.001). Progression was measured by reviewing new ‘hot spots’ on bone scans or any increase over the initial PSA by 25%. Follow-up bone scans revealed four patients (15%) in the orchidectomy-only group had a complete response compared with eight (30%) in the orchidectomy plus lycopene group (p<0.02). PSA level was not statistically different at six months, but at two years the orchidectomy plus lycopene group achieved better PSA response compared with those who had orchidectomy only (78% versus 41%, p<0.001). Pain response was measured through analgesic intake. There was a linear response to treatment in relation to daily requirements for analgesics. When complete response was observed on bone scans, no analgesic requirement was observed in either group. However, the group taking lycopene had more patients who did not require analgesics than the group having orchidectomy alone (25% versus 15%, p value not reported). There was also a statistically significant improvement in peak urine flow rates in the lycopene group with acorresponding benefit in obstructive symptoms (p<0.04). The result of this small study would appear to encourage further investigation of lycopene in the management of advanced prostate cancer.
Studies on vitamin D revealed conflicting results. One showed a benefit for survival and the other found excess deaths in patients receiving vitamin D supplements. Reddy et al examined the use of high-dose vitamin D supplements in combination with weekly docetaxel versus docetaxel alone in 250 patients with metastatic androgen-independent prostate cancer. The combination treatment resulted in significantly better survival, with a 33% (95% confidence interval:0 3 to 55%) relative reduction in risk of death in this group (median survival 23.5 months versus 16.4 months, p=0.04). Vitamin D supplementation was observed to increase the duration of freedom from skeletal morbidity, although not significantly. The time to a PSA response, tumour response rate and proportion of patients with a PSA decrease of at least 50% were not significantly different. Overall, patients in the vitamin D and docetaxel arm suffered fewer side effects than the docetaxel alone group (27% versus 41%, p=0.05). Noticeably, the rate of thrombotic events was lower in the vitamin D arm (2% versus 9%, p=0.02). However the risk of myelosuppression and infection rates was not significantly different. A larger trial comparing the combination of calcitriol and docetaxel with docetaxel alone was terminated in the United States of America because of excess deaths in the calcitriol arm (NCT 0027333, RCT, USA). This illustrates the need for all studies to be published, no matter the outcome of the results or whether they were terminated early due to safety concerns. The difficulty or happenstance in accessing readily available information in trials ‘gone wrong’ is a concern.
The addition of ellagic acid to estramustine and vinorelbine did not significantly improve survival among 48 consecutive patients with hormone-resistant prostate cancer in a study by Falsaperla et al. The proportion of patients in the ellagic acid group with a complete or partial PSA response was higher, and fewer had progressive disease (p=0.03). Analgesic use decreased more in the ellagic acid group (75% versus 42%, p=0.04). There were no significant differences in PSA decrease, and the significance level for duration of pain response was not reported. There were no significant differences in the rate of grade 3 or 4 toxicity in the ellagic acid group except for anorexia, where the rate was lower. It should be noted that ellagic acid is not presently available in Australia.
Kranse et al conducted a double-blind randomised placebo-controlled two-arm cross-over intervention study of the dietary supplement, verum, in 37 prostate cancer patients with no systemic treatment and a rising PSA. The study measured the rate of change of serum concentration of total and free PSA and serum levels of male sex hormones dihydrotestosterone and testosterone. While total PSA doubling time was unaffected, free PSA increased during the placebo phase and decreased during the verum phase (p=0.02). A significant decrease in both total and free PSA was observed (p=0.04) in 21 of 32 men in whom the free androgen index decreased. Survival, toxicity and pain were not reported in this study and there was no significant effect on disease progression.
A recent systematic review of dietary prevention and treatment of prostate cancer advises that doctors must ensure that excessive amounts of dietary supplements should be avoided as adverse events may follow such consumption.
For those requiring a broader review of complementary medicines, there was a National Prescribing Service (NPS) Review in March 2009. (NPS is an independent non-profit organisation for quality use of medicines and is funded by the Australian Government Department of Health and Ageing.)
Also refer to: Memorial Sloan-Kettering Cancer Center for cancer information about herbs, botanicals and other products at http://www.mskcc.org
"Understanding Complementary Therapies: A guide for people with cancer, their families and friends", Cancer Council New South Wales October 2008 at www.cancercouncil.com.au
Advanced Prostate Cancer: A guide for men and their families. Australian Prostate Cancer Collaboration, Australian Cancer Network. 2009. In press.
Evidence summary and recommendations
|A small single RCT found lycopene in addition to orchidectomy has been demonstrated to improve survival, decrease progression and result in better PSA response than orchidectomy alone.||II|||
|There are contrasting results from two studies on the benefit of vitamin D (calcitriol), with one reporting a survival benefit and the other being terminated due to excess deaths in the calcitriol group.||II||, |
|The dietary supplement, verum, may decrease free PSA levels and androgen levels.||II|||
|There is no clear benefit from vitamin D, lycopene or verum in relation to pain relief.||II||, |
|There is a paucity of information on the toxicity of dietary supplements in advanced prostate cancer.||II||, , |
|Calcitriol in combination with docetaxel chemotherapy is not recommended on the basis of a large randomised trial which found excess mortality.||A|
|There is insufficient evidence to make any recommendations on dietary supplements in relation to quality of life, pain relief and toxicity.||C|
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- Kemper KJ, Cassileth B, Ferris T. Holistic pediatrics: a research agenda. Pediatrics 1999 Apr;103(4 Pt 2):902-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10103329.
- Oh WK, Kantoff PW, Weinberg V, Jones G, Rini BI, Derynck MK, et al. Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J Clin Oncol 2004 Sep 15;22(18):3705-12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15289492.
- Ansari MS, Gupta NP. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int 2003 Sep;92(4):375-8; discussion 378 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12930422.
- Reddy GK, Tyagi PT. Clinical Prostate Cancer: Highlights from ASCO May 2005 and 2005 ASCO Prostate Cancer Symposium. Interim Results of the Phase ll Randomised ASCENT Trial of High-Dose Calcitriol and Docetaxel in patients with Androgen Independent Prostate Cancer. 2005.
- Beer TM. ASCENT: the androgen-independent prostate cancer study of calcitriol enhancing taxotere. BJU Int 2005 Sep;96(4):508-13 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16104901.
- Marketwire. Novacea Halts ASCENT-2 Trial in Advanced Prostate Cancer. 2007 Oct 5 Available from: http://www.marketwire.com/press-release/Novacea-Halts-ASCENT-2-Trial-in-Advanced-Prostate-Cancer-788553.htm.
- Falsaperla M, Morgia G, Tartarone A, Ardito R, Romano G. Support ellagic acid therapy in patients with hormone refractory prostate cancer (HRPC) on standard chemotherapy using vinorelbine and estramustine phosphate. Eur Urol 2005 Apr;47(4):449-54; discussion 454-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15774240.
- Kranse R, Dagnelie PC, van Kemenade MC, de Jong FH, Blom JH, Tijburg LB, et al. Dietary intervention in prostate cancer patients: PSA response in a randomized double-blind placebo-controlled study. Int J Cancer 2005 Feb 20;113(5):835-40 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15499622.
- Ma RW, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. J Hum Nutr Diet 2009 Jun;22(3):187-99; quiz 200-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19344379.
- National Prescribing Service. Review of the Quality of Complementary Medciines Information Resources: Summary Report. National Prescribing Service Limited 2009 Mar Available from: http://www.nps.org.au/__data/assets/pdf_file/0005/69656/CMsInfoSummary.pdf.