Christine Ambrosone, PhD, on New Study About Dietary Supplements During Chemotherapy

Although it is common for cancer patients to use dietary supplements after a cancer diagnosis, there are concerns that supplements, and especially antioxidant supplements including vitamins A, C, and E, could interfere with the cytotoxic effects of chemotherapy by generating reactive oxygen species. Results from previous studies have suggested poorer outcomes after chemotherapy associated with supplement use. To address this question prospectively, a team queried participants in the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) clinical trial about their supplement use at the start and completion of chemotherapy. The resulting study in the Journal of Clinical Oncology reported that use of antioxidant supplements before or during chemotherapy was associated with a 41% increase in recurrence risk, with a similar but weaker association with mortality. Non-antioxidant supplements including omega-3 fatty acids, iron, and B12 were also linked with poorer outcomes.

In the following interview, the study's lead author, Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center in Buffalo, New York, and co-leader of the Cancer Center Support Grant Population Sciences Program, elaborated on the findings from the observational study.

Why do you think the use of dietary supplements after a cancer diagnosis is so common among patients?

Ambrosone: First of all, I think supplement use is pretty common overall in the general population. In many circumstances for cancer patients, it may just be that they continue to use supplements that they had previously taken. There are probably many individual reasons for taking dietary supplements specifically during chemotherapy. Cancer patients may take them under the assumption that they may be improving their general health, especially during a time when the body is clearly stressed, such as during cancer treatment.

If patients are experiencing lack of appetite during chemotherapy, they may believe that dietary supplements may compensate for vitamins they are not getting in their diet. There have also been some beliefs that dietary supplements, especially high dose, may increase the efficacy of treatment. Another reason patients may take supplements could be to reduce adverse side effects from treatment, such as anemia and peripheral neuropathy.

What have previous studies reported about supplement use during chemotherapy, and what does your study add?

Ambrosone: The majority of studies in the past have not been able to assess use precisely during chemotherapy. Furthermore, for the most part, patients may have had a range of disease characteristics in these studies and received different treatment regimens. The few studies that were able to query patients during chemotherapy have had mixed results.

Our study results are relevant for women with high-risk breast cancer who received doxorubicin, [cyclophosphamide], and paclitaxel. With the caveats in mind that this is an observational study and the findings of use of "any antioxidant" were of borderline significance (P=0.06), though, this study indicates that use of some supplements during chemotherapy (antioxidants, B12, and iron) may be associated with poorer outcomes.

How should doctors assess and discuss the use of supplements during chemotherapy with patients?

Ambrosone: Only a randomized controlled trial of supplements could clearly answer this question. Thus, we view our study results as contributing to the literature and are not suggesting that clinicians base recommendations to their patients upon the results of this one study.

I'd like to stress that this is an observational study embedded in a SWOG cooperative group trial (S0221) where we asked patients about their habits and use of supplements before and during chemotherapy. As an observational study, it is always subject to bias. Patients may under-report or over-report usage. Because of small numbers of patients who used supplements during treatment in this study (less than 20%), we were not able to separate out according to dosage. Importantly, it is not clear if the associations between supplement use and outcomes are causal -- there may be other factors among these patients that are actually driving the relationships. For example, patients in poorer overall health who get little physical activity may be more likely to take dietary supplements and also more likely to have poorer outcomes.

How does your study methodology differ from other observational studies evaluating supplements and cancer outcomes?

Ambrosone: As noted above, this study was conducted in the context of a clinical trial for high-risk breast cancer, with the description, consent, and contact information embedded in the consent for the clinical trial. Patients were queried about their supplement use before registration to the trial and again when chemotherapy was completed. Data were also collected on other factors that might impact outcomes, such as smoking, alcohol consumption, body size, and physical activity, so that we could take those factors into account.

All patients received the same chemotherapy agents but at different dosing schedules, and patients were removed from the trial if there were notable treatment delays due to toxicities. Data on outcomes were ascertained in the context of the cooperative group trial. These are strengths of this particular study design.

When will the DELCaP study be completed, and do you expect it will confirm these results?

Ambrosone: We have concluded the DELCaP study, although there may be additional follow-up for patient outcomes in the trial, which could either strengthen or weaken the study findings. Patient habits after the questionnaire study ended, however, could influence outcomes and we would not have that data available. Additional studies with the same methodology would be needed to confirm the findings.

Our conclusion in the paper was that results from this study should be considered in the context of the rest of the literature, and clinicians should consider the entire body of evidence when making suggestions to their patients, taking into account their specific needs. This is particularly true for use of iron supplementation to treat anemia, where the benefits may outweigh the potential risks.

You can read the abstract of the study here and read a critique about the clinical implications here.