Effect of YH0618 soup on chemotherapy-induced toxicity in patients with cancer who have completed chemotherapy: study protocol for a randomized controlled trial

According to the data from the WHO’s World Cancer Report 2014, there are an estimated nearly 25 million cancer cases that will occur over the next two decades worldwide, a rise of 75 % [1]. Because of advances in cancer diagnosis and treatment, the survival rate of patients with cancer has been increasing, but the side effects of these treatments, especially chemotherapy, are obvious [2]. Chemotherapy, as a standard regimen, has been used for treating cancers for 70 years. However, in recent years, there is a controversy as to whether it should continue to be used because it causes major side effects, especially toxicity. However, as there is no better regimen to replace chemotherapy, searching for safe and effective ways to ameliorate chemotherapy-induced toxicity has become an urgent issue in the cancer research area.

Chemotherapy-induced dermatologic toxicity is one of the most obvious toxicities, and it can cause considerable cosmetic concern, pain, infection, and functional impairment, and it further impact patients’ quality of life, although it is rarely life-threatening [3, 4]. Its symptoms mainly include pruritus, bullous dermatitis, dry skin, skin pain, paronychia, skin infection, acneiform rash, alopecia, nail discoloration, and nail loss [5]. Low-grade symptoms, such as nail ridging and nail discoloration, can impact beauty and quality of life. Medium-grade symptoms like painful blisters and intense pruritus may also interfere with treatment, resulting in dose reduction or interrupting treatments. Some symptoms may even continue after treatment ceases. Dermatologic toxicity is a major side effect of more than 30 anticancer agents, such as antimetabolites, hormonal agents, topoisomerase-interacting agents, and taxanes; of these taxanes and anthracyclines are the main chemotherapy drugs causing these symptoms [6, 7]. Taxanes are microtubule-stabilizing agents, including paclitaxel, docetaxel, and cabazitaxel, which can stabilize GDP-bound tubulin in the microtubule, therefore interrupting cell division and causing cell death [8]. Anthracyclines are one of the most effective chemotherapeutic drugs and are used to treat many cancers, like lymphomas, leukemias, breast cancer, uterine cancer, ovarian cancer, and lung cancer. The mechanisms of anthracyclines include four pathways. Anthracyclines directly inhibit the synthesis of DNA and RNA by inserting themselves in between nucleotides, thereby interfering with replication and transcription [9]. They also inhibit topoisomerase II, thereby generating reactive oxygen species that damage DNA and cell membranes, or preventing the relaxing of supercoiled DNA and thus blocking DNA transcription and replication [10]. They can also induct histone eviction from chromatin, deregulating DNA damage response, epigenomes, and transcriptomes [11].

Recently, multiple options for reducing chemotherapy-induced dermatologic toxicity have been investigated, but there are no acknowledged and standard treatments. Lacouture et al. [4] found the incidence of grade 2 skin toxicities during the 6-week skin treatment period was 29 % in the pre-emptive group and 62 % in the reactive group. A prospective study demonstrated that ice packs could reduce the incidence of hand-foot syndrome in patients treated with liposomal doxorubicin [5]. In contrast, no significant differences were determined between hand conditions in terms of time to event, nor in terms of toxicity, in cryotherapy and control groups in a randomized control trial [12]. Oral pyridoxine also failed to prevent capecitabine-associated hand-foot syndrome [13].

Chemotherapy-induced myelosuppression, hepatotoxicity, and nephrotoxicity are also common, and they are significant complications affecting the treatment of cancer patients. Moreover, from the view of Chinese medicine, the liver and kidneys are the main organs responsible for detoxification and purification of the blood. Deficiencies of the liver and kidneys lead directly to fatigue, which is also an obvious symptom of cancer patients who just completing chemotherapy. So we believe that dermatologic toxicity and fatigue are a reflection of hepatotoxicity and nephrotoxicity.

Recent attempts to reduce toxicity by using individual compounds have been unsatisfactory [14], and there is also concern about whether using Chinese herbs will cause hepatotoxicity and nephrotoxicity or interactions with anticancer agents [15]; therefore, medical food is the best choice. YH0618, a prescription, has showed efficacy in reducing chemotherapy-induced toxicity through long clinical practice. YH0618 consists of four medical foods (such as black soybeans) which are recommended by clinicians for patients with cancer, and all components have a history of safe use in other foods. Besides, each of the components possesses a distinct pharmacological profile, including removing free radicals in the body, regulating the immune system, preventing cancer, detoxifying, and enhancing taste, etc. [16‐18]. Black soybean, as the monarch drug in the prescription, has been used for detoxification over the millennia in China. Modern research has further explored its active compounds and mechanisms in detoxification. Liao et al. [19] found that a novel polysaccharide of black soybean could improve 5-flurouracil- and irradiation-induced myelosuppression in animal experiments. Anthocyanins, which are the main active compounds in the black soybean seed coat, are water-soluble and possess significant anticancer [20], antioxidation [21], liver-protective [22, 23], and kidney-protective effects [24] in vitro and in vivo experiments. Over long clinical observation, YH0618 soup has been proved to be effective in reducing chemotherapy-induced toxicity by clinical observation, but there is not yet any scientific research exploring the effects of YH0618 soup in patients with cancer. Therefore, this study will be conducted to further verify the benefits of YH0618: the hypothesis is that YH0618 soup would ameliorate chemotherapy-induced toxicity including dermatologic toxicity, hematotoxicity, hepatotoxicity, and nephrotoxicity in cancer patients who have completed chemotherapy. Moreover, since little research has explored the role of medical food intervention in reducing chemotherapy-induced toxicity, and YH0618 is a safe medical food, the project will bring huge benefits to patients with cancer. The YH0618 prescription has the potential to become a standard alternative intervention strategy in providing care to these patients.