4. Discussion
In this study, more than eight among ten of cancer patients used herbal medicines during chemotherapy courses and eight patients out of ten patients with the history of herbal medicine consumption had potential herb-drug interactions. Potential moderate herb-drug interactions occurred in all patients, while potential minor herb-drug interactions happened in a third of patients. Based on the findings, chamomile is the most popular herbal medicine and green tea leads to frequent potential minor and moderate herb-drug interactions. The number of chemotherapeutic agents, number of herbal medicines, gastrointestinal cancers, thorax cancers, IV clinical stage, unclear recurrence status and the experience of pain during chemotherapy courses were determined as the predictors of herb-drug interactions among cancer patients.
High prevalence of using herbal medicines in combination with conventional treatments is an important issue which has been addressed in many studies with different population (28-31), a finding that has also been discussed in our study. The majority of cancer patients used herbal medicines during chemotherapy courses and according to our previous study, this consumption was also hidden from physicians’ view (32). Patients, regardless of current treatments, use herbal medicines for a variety of reasons. For example, patients believe that they can use herbal medicines without trouble, because they are natural, effective in treating diseases and they can reduce cancer symptoms, and they have no side effects (33, 34). These patients have mistaken beliefs about herbal medicines, because herbs when used in combination with drugs have an influence on induction and inhibition of metabolic enzymes and finally on drug absorption (35). Herb-drug interaction is the consequence of this combination and may lead to unexpected adverse clinical outcomes (36, 37) such as hepatotoxicity (38). According to related studies, the prevalence of herb-drug interactions among cancer patients is considerable (39) and it varies from 2.3% (40) to 25% (41) and 46% (42). The findings of our study showed that more than three quarters of cancer patients had herb-drug interactions and this prevalence was higher in comparison to other studies. Some of the reasons for this discrepancy was related to more consumption of herbal medicines by our patients, consumption herbal medicines which lead to herb-drug interaction such as garlic, green tea (43) and chamomile (44) and identification of new pairs of herb and drugs which resulted to interactions over time.
An important issue in Drug Related Problems (RDPs) such as drug interactions is related to Narrow Therapeutic Window (NTW) of some drugs such as chemotherapeutic agents (45, 46). These drugs with a small difference between the minimum effective range and the minimum toxic range have steep dose-response relationship and they must be monitored carefully (47, 48), because small changes in their dose or plasma concentration can lead to life-threating toxicity or sub-optimal therapy and under treatment of cancer (48, 49). But how dose herbal medicines interact with these drugs? The drug clearance is the key point in this story and the metabolic modification of some enzymes such as CYP and UGT and drug uptake and efflux transporter are involved in this cycle (50, 51). The clearance of 70% of drugs depend on CYP enzyme and the most important drug interactions caused by inhibition and induction of this enzyme as well as UGT in the first and second phases of drug metabolism especially chemotherapeutic agents (52, 53). The results of our study are consistent with similar related studies (54, 55) indicating that most of herb-drug interactions are caused by inhibition or induction of CYP3A4 enzyme. As regards, the metabolized of many drugs depend on this enzyme, induction or inhibition of it can lead to unexpected toxicity and under treatment of cancer. In this regard, physicians and other health workers must pay more attention and had better prevent patients from using herbal medicines in combination with other drugs.
We also found that the number of herbal medicines and also chemotherapeutic agents as predictors increased the odds of herb-drug interactions among cancer patients. This result is in line with the study conducted by Levy et al. (2017) on hospitalized patients (56) and the study by Chi et al. (2020) on community-dwelling older adults (57). The reason for this event is clear and by increasing the number of each drug (herbal or chemotherapy), the odds of herb-drug interaction subsequently increased. Another predicting factor was experiencing pain during chemotherapy which was associated with increased odds of herb-drug interactions. The results of related studies show that considerable proportion of patients with chronic pain used CAM (58, 59). Licorice (60), chamomile (61) and peppermint (62) as analgesic, are popular herbal medicines and interact with chemotherapeutic agents. As a result, the experience of pain causes the use of herbal medicines and the herb-drug interaction is the potential outcome of this usage.
Type of cancer and advanced cancers were the other predictors of herb-drug interactions in this study. According to the results, patients with gastrointestinal cancers and thorax cancers had lower odds of herb-drug interactions versus patients with breast cancer. This difference can be justified by two reasons. First, the majority of patients with breast cancers are females and females are more likely to use herbal medicines in combination with other drugs (63, 64). Therefore, the odds of herb-drug interactions for females are more than males which was confirmed by results of bivariable logistic regression in our study. The second reason was related to the type of drugs used for patients with breast cancers. Tamoxifen, Letrozole and Exemestane are common drugs which are usually prescribed for postmenopausal breast cancer patients. These patients used specific herbal medicines to reduce complications of menopause such as licorice, fennel and valerian, the supplement estrogenic activity which interact with chemotherapeutic agents (65, 66). In contrast, patients with advanced cancers had greater odds of herb-drug interaction versus other patients. The results of one study showed that patients with advanced cancers were inclined to use CAM and the prevalence of using herbal medicines among these patients were considerable (67). There are several reasons for these patients to use herbal medicines. They look for a way to reduce severe symptoms of cancer and also side effects of chemotherapy courses. Also, they hope to live longer.