Supportive Care in Cancer

Transcription

1 Supportive Care in Cancer

2 in Cancer Springer-Verlag /s Original Article The use of dietary supplements in a community hospital comprehensive cancer center: implications for conventional cancer care Digant Gupta 1, Christopher G. Lis 1, Timothy C. Birdsall 1 and James F. Grutsch 1 (1) Cancer Treatment Centers of America (CTCA) at Midwestern Regional Medical Center, Zion, IL, USA Authors Contact: Digant Gupta digant.gupta@mrmc-ctca.com Phone: Fax: Supportive Care in Cancer, Volume 13, Issue 11, Nov 2005, Pages Received: 4 January 2005 Accepted: 7 April 2005 Published online: 23 April 2005 Abstract Goals of work There is little data on the prevalence of use of dietary supplements in cancer, especially in light of the growing evidence that some dietary supplements can have adverse interactions with conventional cancer treatment. The purpose of this study was to investigate the use of dietary supplements among adult cancer patients in a community hospital comprehensive cancer center. Patients and methods A survey of 227 new adult cancer patients presenting for treatment for the first time at Cancer Treatment Centers of America at Midwestern Regional Medical Center, between November 2001 and October Patients completed the McCune Questionnaire, a validated instrument that captures information on the use of 56 dietary supplements in cancer, at admission to the hospital. Results Of the 227 patients, 73% used some form of dietary supplements during the 30 day period before the survey was conducted. Dietary supplement use was significantly higher (p = 0.04) in patients with colorectal (80%) and breast (75%) cancer as compared to patients with lung cancer (53%). Patients with stage II (86%) and III (76%) disease at diagnosis were more likely (p = 0.02) to use dietary supplements as compared to those with stage I (71%) disease at diagnosis, while those with stage IV (61%) disease at diagnosis were least likely to use them. Of the 80 patients who had received chemotherapy within the last 30 days, 71% had also used dietary supplements in that timeframe and 25% had consumed one or more herbal therapies that are suspected to

3 have adverse interactions with chemotherapy. Of the 57 patients combining chemotherapy with dietary supplements, 52.6% did not consult a healthcare professional. Conclusions In our study, twenty-five percent of patients receiving chemotherapy were concurrently using dietary supplements suspected to have adverse interactions with chemotherapy, usually relying on information sources other than healthcare professionals. Given the prevalence rates of these agents, healthcare providers should systematically inquire about them, and consider the potential for drug-dietary supplement interactions in treatment planning. Keywords Dietary supplements - Cancer - Chemotherapy - Interaction Introduction The use of complementary and alternative medicine (CAM) in the USA continues to attract an increasing level of attention from the medical community and the public [1, 2]. Dietary supplements, which include vitamins, minerals, and herbs, are among the most commonly used CAM therapies. With a larger number of the US population using dietary supplements combined with allopathic treatments, the risk for dietary supplement drug interaction is a growing concern [ 3 5]. This risk becomes greater for cancer patients re ceiving chemotherapy agents, as these agents have a narrow therapeutic index [6]. In fact, a few herbal therapies such as garlic, ginkgo, Echinacea, ginseng, valerian, kava, grapeseed, soy, and St.-John s-wort have been identified to have potentially adverse interact ions with some co mmonly used chemotherapy ag ents [4]. Consequently, the possibility of unrecogniz ed herb drug interactions is emerging as a significant concern for treating oncologists. Although several studies have reported on the utilization of dietary supplements as part of an overall assessment of C AM use [7 18], only a few studies published to date have reported exclusively on dietary supple ment use in a cancer treatment setting [6, 19]. The purpose of this study was to investigate the use of dietary supplements in a community hospital comprehensive cancer center examining the ( 1) prevalence and patterns of use, (2) characteristics of users, (3) reasons and information sources of use, and (4) perceived benefits of use. Patients and methods Patient population The study was conducted on a convenience sample of new cancer patients who presented for the first time to Cancer Treatment Centers of America at Midwestern Regional Medical Center, Zion, IL, between November 2001 and October Criteria for entry into the study included a minimum age of 18 years, diagnosis of any type of cancer, a life expectancy of at least 2 months, and literacy in the English language. Patients with any tumor type and stage of the disease at diagnosis were eligible for the study. Patients were

4 excluded if they were unable to give informed consent or understand or cooperate with study conditions. A trained clinical coordinator described the study and determined eligibility after patients signed in at the clinic. As part of the consent process, patients were assured that refusal to participate in the study would not affect their future care in any way. The study was approved by the Institutional Review Board at Midwestern Regional Medical Center. Questionnaire A self-administered questionnaire developed and validated at the University of Washington School of Pharmacy, which captures information on the use of 56 dietary supplements (Table 1) within the preceding 30 days, was used. Space was allowed to indicate any other dietary supplement use that was not included in the questionnaire. This questionnaire collected data on the dose and frequency of dietary supplement use and the specific agents used by the patient. It also gathered relevant demographic and clinical data, such as age, gender, ethnicity, education, family income, and treatment history. In addition, the questionnaire obtained information on the types of providers most often sought for CAM consultations and rationale for dietary supplement use along with their perceived benefits. Patients recorded their own responses directly onto the questionnaire, which was returned to the clinical coordinator within 24 h. Table 1 Dietary supplements listed in the questionnaire 714-X Evening primrose Milk thistle Algae Garlic Multiple vitamin Antineoplastons Geniposide Mushroom Beta carotene Germander Pokeroot Black Cohosh Ginger Pycnogenol Bovine cartilage Ginkgo biloba Quercetin Cancell Ginseng Sassafras Cell forte/ip6 Glucosamine Saw palmetto Chamomile L-Glutamine Selenium Chlorophyll Goldenseal Shark cartilage CoEnzyme Q10 Green Tea Extract St.-John s-wort Coltsfoot Hydrazine sulfate Valerian Comfrey Iscador/mistletoe Vitamin A Creatine Jin Bu Huan Vitamin B6 DHEA Kava Kava Vitamin B12 Dong Quai Kelp Vitamin C Echinacea Licorice root extract Vitamin E EPA (fish oil) Melatonin Zinc

5 Ephedra MGN-3 Statistical analyses All data were analyzed using SPSS 11.5 (SPSS Inc., Chicago, IL, USA). Dietary supplement users were defined as those who had used at least one dietary supplement in the past 1 month. Prevalence, types, reasons, information sources, and perceived benefits of using dietary supplements were described as percentages. Differences between dietary supplement users and nonusers with respect to demographic and clinical characteristics were evaluated using bivariate chi-square test and t-test for independent means depending upon the underlying distribution of the variables. Logistic regression was used to determine factors predicting dietary supplement use in the last 30 days. The dependent variable (use/nonuse of dietary supplements in the past month) was dichotomous. Independent variables included in logistic regression w ere age, gender, ethnicity, education, income, tumor type, prior treatment history, and chemotherapy use in the last 30 days. All analyses were conducted for overall dietary supplement use and dietary supplement use excluding vitamins. The significance level for all analyses was set at alpha = 0.05, and all tests were two-sided. Results Characteristics of respondents A total of 242 cancer patients were approached in the clinic between November 2001 and October 2003 and were screened for eligibility by the clinical study coordinator. All 242 patients were found to be eligible for participation. Of 242 eligible patients, 227 consented to participate and completed the survey. The final study sample consisted of 227 patients with a respon se rate of 93.8%. Table 2 describes the baseline characteristics of our patient cohort in greater detail. Table 2 Baseline characteristics (N=227) Characteristic Categories Percent Gender Male 40.1 Female 59.9 Did not complete high school 5.7 Education High school 40.1 College or trade school 38.3 Graduate or professional 13.2 Unknown 2.6 Caucasian 91.2 Ethnicity African-American 6.2 Others 2.2 Unknown 0.4

6 Characteristic Categories Percent <$20, $20,000 34, Annual household income $35,000 49, $50,000 64, >$65, Unknown 16.7 Progressive disease 57.3 Prior treatment history Newly diagnosed 28.6 Unknown 14.1 Breast 30.0 Colorectal 17.6 Lung 14.1 Diagnosis Pancreatic 4 Prostate 4 Esophagus 4 Others 23.7 Unknown 2.6 I 12.3 II 21.6 Tumor stage at diagnosis III 18.5 IV 30.4 Unknown 17.2 Yes 35.2 Chemotherapy in last 30 days No 60.8 Unknown 4.0 Dietary suppleme nt use in th e last 30 days Users 73.1 Nonusers 26.9 Dietary supplements use excluding vitamins in the Users 63.9 last 30 days Nonusers 36.1 Prevalence and patterns of dietary supplement use Overall, 166 (73.1%) patients had used at lea st one type of dietary supplement during the last 30 days with the median number of therapies being 6 (range 1 45). When vitamins were excluded, 145 (63.9%) patients had used at least one dietary supplement during the last 30 days with the median number of therapies being 4 (range 1 39). The prevalence of

7 use of overall dietary supplements and their use excluding vitamins in patients who had received chemotherapy in the last 30 days was 71.3% (57/80) and 65% (52/80), respectively. Table 3 describes the number of dietary supplements used by our patients. The ten most commonly used dietary supplements are described in Table 4. The five most commo nly used dietary supplements not included in the questionnaire were calcium (8.8%), magnesium (2.6%), folic a cid (2.2%), Essiac tea (1.8%), and iron (1.8%). Table 5 lists the prevalence of use of herbal remedies suspected to have adverse interactions with conventional cancer treatment [4]. The overall prevalence of use of those therapies was 29.5% ( 67/227) with the median number of therapies being 1 (range 1 7), whereas their prevalence of use in patients receiving chemotherapy in the last 30 days was 25% (20/80) with the median number of therapies being 1 (range 1 4). Table 3 Number of dietary supplements used (N=227) Number of dietary All dietary supplements Dietary supplements excluding supplem ents used (% pat ients) vitamins (% patients) More than Table 4 The ten most commonly used dietary supplements (N=227) All dietary supplements Dietary supplements excluding vitamins Therapy Percentage of patients (%) Therapy Percentage of patients (%) Vitamin C 47.1 CoEnzyme Q Multiple vitamin 46.3 Selenium 22.0 Vitamin E 42.3 EPA (fish oil) 19.8 CoEnzyme Q Garlic 18.1 Selenium 22.0 Zinc 17.2 Beta carotene 22.0 Gr een tea extract 16.7

8 All dietary supplements Therapy Percentage of patients (%) Dietary supplements excluding vitamins Percentage of patients Therapy (%) Vitamin B Milk thistle 12.3 Vitamin B Melatonin 10.6 EPA (fish oil) 19.8 Echinacea 9. 7 Garlic 18.1 Cell forte 7.1 Table 5 Prevalence of use of herbal remedies suspected to have adverse interactions with conventional cancer treatment Therapy All patients (N= 227) (% Chemotherapy in last 30 days (N=80) patients ) (% patients) Garlic Echinacea Ginseng Ginkgo Valerian St.-John s-wort Kava Grape seed extract Soy Characteristics associated with dietary supplement use Using bivariate chi-square analysis, statistically significant differences were noted between dietary supplement u sers and non users with re gard to education, tumor typ e, and tumor stage at diagno sis. Increasing dietary supplement use was seen with higher education. Patients with colorectal and breast cancer were more likely to use dietary supplements as compared to patients with lung cancer. Patients with stages II and III disease at diagnosis were more likely to use dietary supplements as compared to those with stage I disease at diagnosis, whereas those with stage IV disease at diagnosis were least likely to use them. Altho ugh statistically nonsignificant, a t rend of incr easing d ietary supplement use with higher annual income was also observed. A detailed description of differences between dietary supplement users and nonusers with respect to demographic and cl inical variables is shown in Table 6. Table 6 Predictors of dietary supplement use Variable All dietary supplem ents Dietary supplements excluding vita mins

9 Users Nonusers χ 2 p Users Nonusers χ Value p Value Gender Males Females Mean age at diagnosis (std. dev.) (10. 1) (10.8) (9.9) 49.4 (10.9) 0.46 Education Did not complete high school High school College or trade school Graduate or professional Ethnicity Caucasian African-American Asian-American Indian Others Annual household income <$20, $20,000 34, $35,000 49, $50,000 64, >$65, Prior treatment history Progressive disease Newly diagnosed Chemotherapy in last 30 days Yes No , Diagnosis Breast Colorectal

10 Dietary supplements excluding All dietary supplements vitamins Variable p Users Nonusers χ 2 se sers χ Value U rs Nonu 2 p Value Lung Tumor stage at diagnosis I II III IV Logistic regression analysis found the following varia bles to be statistically significantly associated with a more frequent dietary supplement use: graduate or professional education (OR=5.57; 95% CI ) and college or trade school (OR=3.53; 95% CI ) with less than high school as reference; colorectal (OR=3.53; 95% CI ) and breast cancer (OR=2.65; 95% CI ) with lung cancer as reference; and stage II (OR=2.4; 95% CI ) and stage III (OR=1.28; 95% CI ) disease at diagnosis with stage I disease at diagnosis as reference. Table 7 describes these associations in greater details. Table 7 Predictors of dietary supplement use in univariate logistic regression model (N=227) Dietary supplements excluding All dietary supplements vitamins Variable OR 95% CI p Value OR 95% CI p Value Education Did not finish high school a 1 1 High school 1.74 College or trade school 3.53 Graduate or professional Tumor site 5.57 (0.54, 5.64) (1.05, 11.86) (1.22, 25.36) (0.34, 3.51) (0.62, 6.56) (1.00, 18.32) 0.05 Lung a 1 1 Colorectal 3.53 (1.25, 9.99) (1.27, 9.07) 0.02 Breast 2.65 (1.09, (1.38, 7.97) 0.01

11 Variable All dietary supplements Dietary supplements excluding vitamins p OR 95% CI Value OR 95% CI p Value Other 2.78 Tumor stage at diagnosis 6.41) (1.19, 6.49) Stage I a (0.88, 4.55) 0.10 Stage II 2.4 (0.76, 7.5) (0.76, 6.1) 0.14 Stage III 1.2 (0.4, 3.8) (0.4, 2.7) 1.0 Stage IV 0.6 (0.2, 1.6) (0.2, 1.4) 0.22 a Reference category Reasons and information sources of dietary supplement use Patients were asked to supply reasons for dietary supplement use from a list of six predefined reasons in the questionnaire. Each patient selected one or more reasons. One hundred thirty-five (59.5%) patients cited that they used dietary supplements to improve the immune system, 123 (54.2%) to do everything possible, 90 (39.6%) to slow the progression of cancer, 72 (31.7%) to use a more holistic approach, 61 (26.9%) to tolerate chemotherapy, and 19 (8.4%) to use psychological forces. Finally, 24 (10.6%) patients cited numerous other reasons, the most common being to improve general health and well being. Additionally, patients were asked to provide their primary sources of information on dietary supplements. Ninety-two (40.5%) patients obtained information from a health food/nutrition store, 84 (37%) from a friend or relative, 64 (28.2%) from a naturopath, 46 (20.3%) from the Internet, 34 (15%) from newspaper or magazine, 18 (7.9%) from an oncologist, and 17 (7.5%) from television. Finally, 54 (23.8%) patients named a source not included in the choices on the questionnaire, the most common information sources being chiropractor, nutritionist, and pharmacist. Perceived benefits of dietary supplement use Patients were asked to rate the perceived benefits of each dietary supplement used on a scale ranging from 0 to 3 ( don t know, not beneficial at all, somewhat beneficial, and extremely beneficial, respectively). Because most patients used more than one dietary supplement, the perceived benefits varied with each individual therapy. As a result, all responses to the question on perceived benefits for all dietary supplements were combined to derive the overall estimates for perceived benefits. Out of a total of 951 responses, 437 (45.9%) were don t know, 242 (25.4%) extremely beneficial, 237 (24.9%) somewhat beneficial, and 35 (3.7%) not beneficial at all. Overall, a total of

12 96 (42.3%) patients responded don t know, as regards to the perceived benefits of one or more dietary supplements, 58 (25.6%) extremely beneficial, 72 (31.7%) somewhat beneficial, and 14 (6.2%) not beneficial at all. Discussion The purpose of this study was to determine the prevalence and patterns, characteristics, reasons, information sources, and perceived benefits of dietary supplement use in cancer patients at a community hospital comprehensive cancer center. There was a high overall prevalence of dietary supplement use in our patient cohort. One hundred sixty-six (73.1%) patients used at least one dietary supplement within the last 30 days, and when vitamins were excluded, the number of patients using at least one dietary supplement was 145 (63.9%). Comparing the overall prevalence rates across different studies is a significant challenge as studies differ on patient population, survey instrument, sample size, response rate, and definition of CAM. Notwithstanding these limitations, the overall prevalence of dietary supplement use in our study is somewhat higher than that reported by Richardson et al. [16] who found an overall dietary supplement use of 62.6% in a wide variety of cancer patients attending a comprehensive cancer treatment center. On the other hand, a recent study conducted by McCune et al. in 76 cancer patients receiving chemotherapy at a university-based outpatient clinic reported the overall prevalence of dietary supplement use to be 78%. Previous studies have identified numerous predictors of CAM use in cancer, the most common being certain demographic characteristics such as younger age [ 9, 11, 13, 15, 16, 18], female gender [13, 16], higher educational [9, 13, 15, 18], and income levels [9, 11 13, 18]. In our study, we did not find any statistically significant associations between dietary supplement use and age, gender, ethnicity, income, and prior treatment history. However, there was an increasing dietary supplement use with higher education. Although not statistically significant, our study found a trend of increasing dietary supplement use with higher incomes. In addition, we found that colorectal and breast cancer patients were more likely to use dietary supplements compared to lung cancer patients. Patients with stages II and III disease at diagnosis were more likely to use dietary supplements as compared to those with stage I disease at diagnosis, whereas those with stage IV disease at diagnosis were least likely to use them. One potential explanation for a relatively lower use of dietary supplements in patients with stage IV disease could be our clinical observation that these patients have difficulty swallowing the dietary supplements. Although there was no statistically significant association between prior chemotherapy and dietary supplement use, 71.3% (57/80) of patients receiving chemotherapy within the last 30 days also used dietary supplements during that same timeframe, and 65% (52/80) used dietary supplements excluding vitamins. Of the 57 patients who indicated both chemotherapy treatment and dietary supplement use within the last 30 days, 30 (52.6%) did not consult a healthcare professional (oncologists, naturopaths, chiropractors, nutritionists, and pharmacists). This finding has important implications for potential

13 herb drug interactions. The recently published review article by Sparreboom et al. [4] reported the existing data on known or suspected interactions between the most commonly used herbal therapies and conventional chemotherapeutic treatment for cancer. The following herbal therapies were identified as having potential adverse pharmacokinetic interactions with oncology drugs: garlic, ginkgo, Echinacea, ginseng, valerian, kava, grapeseed, soy, and St.-John s-wort. In our study, 25% (20/80) of the patients receiving chemotherapy in the last 30 days consumed one or more of these herbal therapies. These findings confirm the need for better patient physician communication on the use of dietary supplements during cancer treatment. In addition, comprehensive research strategies are urgently needed to more accurately establish the nature and extent of interactions between dietary supplements and oncology drugs. Our study has several strengths. A high response rate of 93.8% minimizes response bias, a significant problem in CAM survey research. The questionnaire used in this study evaluated dietary supplement use restricted to the preceding 30 days only, thereby minimizing recall bias. Also, the questionnaire focused on a broad range of dietary supplements, some of which have been identified as having potential adverse interactions with conventional chemotherapy. However, several limitations of this study must be acknowledged. The patient cohort was limited to only those patients who were English speakers and consisted largely of Caucasians with breast cancer. This study sample, therefore, is not broadly representative of cancer patients in general. Our hospital offers a wide range of integrative cancer treatment options including nutritional, naturopathic, mind body medicine, and spiritual therapies in conjunction with conventional cancer care. It seems likely that many patients seeking care at our hospital have a particular interest in pursuing complementary therapies and may therefore have a higher prevalence of dietary supplement use than the broader population of patients with cancer. There was no attempt to systematically evaluate any differences between the respondents and nonrespondents in this study because the identity of the nonrespondents was unknown to the researchers. Although our study describes the prevalence of use of potentially harmful herbal agents in patients receiving chemotherapy in the last 30 days, we did not have any specific information on the chemotherapy treatments used. This information would have enabled us to more extensively evaluate the potential for herb chemotherapy interactions. Due to missing data on tumor stage for 39 patients, the association of tumor stage with dietary supplement use was based on a sample size of 188 only. Our sample size might not have been large enough to accommodate the number of post hoc subgroup comparisons made within this study. Finally, this study was not an attempt to scientifically evaluate the impact of dietary supplements on cancer but rather to describe what proportion of people with cancer use dietary supplements. In summary, a great majority of patients seeking cancer treatment at our institution use dietary supplements. There is increasing dietary supplement use with higher education. Patients with colorectal and breast cancer are more likely to use dietary supplements than patients with lung cancer, and patients with stages II and III disease at diagnosis are more likely to use dietary supplements than patients with stage I disease at diagnosis. Twenty- five percent of patients receiving chemotherapy are concurrently using dietary sup plements suspected to have adverse interactions with chemotherapy, usually relying

14 on information sources other than healthcare professionals. Given the prevalence rates of these agents, healthcare providers should systematically inquire about them and consider the potential for drug dietary supplement interactions in treatment planning. Acknowledgements We thank Thom Wodek for his contributions in the coordination an d daily operation of the study. We also thank Ashmer Aslam for his assistance with dat a acquisition, database management, and data analysis. Dr. Gupta and Dr. Grutsch had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. This study was funded by Cancer Treatment Centers of America (CTCA). Design and conduct of the study; collection, management, analysis, and interpretation of the data; and prep aration, review, or approval of the manuscript were conducted by the authors of this study, who take responsibility for its content. References 1. Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL (1993) Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med 328: Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M et al (1998) Trends in alternative medicine use in the United States, : results of a follow-up national survey. JAMA 280: Markman M (2002) Safety issues in using complementary and alternative medicine. J Clin Oncol 20:39S 41S 4. Sparreboom A, Cox MC, Acharya MR, Figg WD (2004) Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol 22: Fugh-Berman A (2000) Herb drug interactions. Lancet 355: McCune JS, Hatfield AJ, Blackburn AA, Leith PO, Livingston RB, Ellis GK (2004) Potential of chemotherapy herb interactions in adult cancer patients. Support Care Cancer 12: Ashikaga T, Bosompra K, O Brien P, Nelson L (2002) Use of complimentary and alternative medicine by breast cancer patients: prevalence, patterns and communication with physicians. Support Care Cancer 10:

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