Use of Supplements by Japanese Cancer Patients Receiving Outpatient Cancer Chemotherapy

Introduction

Supplements play a role in complementary and alternative medicine (CAM) in cancer patients. ^{1 –3} Cancer patients use supplements to increase treatment efficacy, and reduce symptoms related to their treatment. ^2,3 However, in vitro and animal model studies indicate the potential risk of interaction between many supplements and anticancer drugs. ^{4 –6} Therefore, possible interactions should be considered in the clinical setting.

Since epidemiologic studies on supplement use in cancer patients were mostly conducted in Western countries, ^2,3 the prevalence and characteristics of supplement usage in Japanese cancer patients were investigated. In Japan, supplements are defined as vitamins, minerals, and items derived from natural products. The potential interaction between supplements and anticancer drugs based on a literature search is also reported.

Methods

This study was conducted at an outpatient cancer chemotherapy center at Kobe City Medical Center General Hospital in 2015. All of the 239 patients who attended the chemotherapy center were enrolled after obtaining their verbal consent. Basic information (age, sex, type of cancer, and modality of chemotherapeutic regimen) was drawn from patients' charts. Data about the supplements used, the reason for taking supplements, consultations with medical staff, and any side effects were retrieved through face-to-face interviews. Independently, 1108 subjects free from cancer recruited from visitors to a health management center at Kyoto Katsura Hospital in 2014 served as the control. The Ethical and Epidemiological Committee of Nara Women's University approved both studies. Differences in categorical variables were examined using the chi-square test, and differences in continuous variables were examined using the unpaired t test. Statistical analyses were performed using Excel Statistics (version 2012). A p-value of <0.05 was considered significant.

To investigate potential interactions between supplements and anticancer drugs, the PubMed database was searched at the end of August 2016 using combinations of the MeSH terms: “cancer,” “anti-cancer drugs” or “chemotherapy,” “dietary supplements,” and “interaction.” Both preclinical and clinical articles were retrieved to create a list of potential interactions.

Results

The prevalence of supplement use was significantly higher among the cancer patients than the control subjects. Supplement use did not differ significantly between male and female cancer patients, but was significantly higher among women in the control group. Supplement usage did not differ with age in either group, nor among different types of cancer. Garlic, propolis, fucoidan, agaricus, and turmeric were used more frequently by the cancer patients. Vitamins, green juice, calcium, and glucosamine were used more frequently by the control subjects. The main reason why cancer patients took supplements was as a form of cancer treatment; in contrast, the control subjects took supplements to maintain their general health. A similar proportion of each group consulted medical staff about their supplement use (Table 1).

There were 67 instances of potential interactions between supplements and anticancer drugs, involving 47 patients. Of the 67 potential interactions, 41 (61.2%) were classified as augmentation and 26 (38.8%) as attenuation. The details of the potential interactions are described in Table 2.

Discussion

The prevalence of supplement use by cancer patients has been reported to vary (35%–96%) according to the year of publication, ethnicity, and type of cancer. ^{1 –5} A prevalence rate of 53.1% was found among cancer patients, which was significantly higher than the control subjects. No sex differences were found. The prevalence of supplement use in the nationwide study using 3100 cancer patients by Hyodo et al. was calculated as 43.0%. ¹ Their study mainly focused on CAM use in general without reporting any details of supplement use, although this study focused specifically on supplements use in cancer patients. Notably, this study has several advantages: (1) an interview method used for data collection, (2) inclusion of the control group from the general population, and (3) the analysis of the potential interaction between supplements and anticancer drugs. The nondisclosure of CAM or supplement use to medical staff is problematic. ⁷ The disclosure rate was low, but it was comparable with the control. Japanese cancer patients tended to choose specific supplements that have been advertised as effective for cancers, for example, garlic, propolis, fucoidan, and agaricus.

Theoretically, the association of antioxidative effects, cytochrome P450 families, and P glycoprotein has been proposed for potential interactions. ^{4 –6} A total of 67 instances of potential interactions were found in 47 patients. Previous studies reported the prevalence of interactions as 13.9% in 806 patients ⁴ and 50.3% in 84 patients. ⁶

As the number of cancer patients grows worldwide, the use of supplements can be expected to also increase. Oncology health professionals need to engage in respectful dialogue with cancer patients about their interest and use of supplements and become more knowledgeable about the potential effects of supplements, including interactions with cancer treatment. ⁸