name: Jonty Vincent (firstname.lastname@example.org) organisation: h/n cancer radiotherapy patient in Brisbane
With regards to beta carotene intake your Q21 summary statements are at odds with your recommendations.
Your Summary: There are two level II neutral quality studies reporting on beta carotene. The first demonstrates fewer adverse effects associated with high dietary beta carotene intake, higher plasma beta carotene levels and improved survival . A second neutral study reported reduced mucositis, but no effect on survival .
Your Recommendation: Beta carotene (30mg/d) may be associated with reduced survival or recurrent disease. B
This is confusing.
The references are [13, 15].
The title of 13 "Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients" maybe the cause of the confusion as on initial inspection this title draws an incorrect negative association between "acute adverse effects of radiation therapy" and "beta carotene". The actual article makes the opposite assertation - "This study suggests that a higher usual dietary beta carotene intake can reduce the occurrence of severe adverse effects of radiation therapy and decrease local cancer recurrence." in direct conflict to your recommendation.
Unable to find the text for reference 15.
Does your search include "Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8" "Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1." Simone CB 2nd, Simone NL, Simone V, Simone CB. Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8. Review. PMID: 17283738 [PubMed - indexed for MEDLINE] this article conflicts with your recommendation but would agree with your summary.
Thank you for your comments. The section on beta carotene has been reviewed, and a correction to the recommendation statement has been made. Additional information on the withdrawal of the use of beta carotene in these trials has also been included and the reasons why.
Thank you for also highlighting the other paper Simone et al 2007. This has been reviewed by the committee, and would have been excluded from the initial literature search as it is not a systematic review of RCT’s, and so would be classed as level V evidence (expert opinion) and therefore this type of paper can have a high level of bias in methodology and interpretation of results. Using our assessment tool, we reviewed the quality of the paper to be negative. The literature search was only current until 2003, and so missed several key articles that had been published since in this area. Therefore no further changes have been made to the recommendations.
Teresa Brown, on behalf of the authors
Hi Teresa, Thanks for your response. I gather your literature search has been updated to search beyond 2003 as I now see references to more recent studies e.g. under Carotenoids there is a 2010 reference to Nutr Cancer 2010;62(3):322-8. Interestingly COSA's latest (Jul 2011) Cancer Forum issue has an article "After the storm: nutrition after cancer treatment" stating "...while treatment with β-carotene, vitamin A, and vitamin E may increase mortality." referencing yet another source, this time the Journal of American Medical Association. 2007; 297(8):842-857. - Bjelakovic G, Nikolova D, Gludd L, Simonetti R, Gludd C, et al. If you read the reference it states "....In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08)". It's curious that a data finding in trials with such a large sample (180,000+) of significantly increased mortality is so diluted in the summary to say "Treatment with beta carotene, vitamin A, and vitamin E may increase mortality.", I think a statistician would impart greater confidence in the data, but alas we live in a world full of uncertainty.
I have had a quick look at the Vit E issue again and have come across reference to another article which may strengthen the recommendations against use of Vit E. Bairati Int J Cancer 2006 119(9) 2221-2224 (see attached – same person involved in 4 of the other articles included). All cause mortality was significantly higher for the supplementation group, and there was a trend towards significance for a number of other subsets – all against supplementation.
I have attached a review article which may be of use for any further reviews. Lawenda 2008.
I like the first paragraph – I remember discussing this in the teleconference but I think you have worded it well – glad you put the pharmacists first!
Brett Janson Senior Clinical Pharmacist Peter MacCallum Cancer Centre
Thank you for your comments and suggestions. The Bairati 2006 paper will be formally reviewed and included.
The Lawenda 2008 review article will be considered for inclusion. It is a good systematic review of RCT’s of antioxidants during treatment, but is not specific to H&N cancer.
Teresa Brown, on behalf of the authors