Concentrated Complex Plant Dietary Elements for Chemotherapy-Induced Diarrhea

Gastrointestinal cancer ranks high in both incidence and mortality, as one of the major health threats worldwide. Chemotherapy with or without surgery is the first line of treatment for gastrointestinal cancer. Chemotherapy involves the use of powerful cytotoxic drugs to stop tumor growth by targeting rapidly dividing cells through various mechanisms, and has greatly improved overall survival of patients. Simultaneously, chemotherapy often affects rapidly dividing gastrointestinal epithelial cells, leading to gastrointestinal symptoms, and diarrhea is a common adverse reaction in cancer patients receiving various chemotherapy regimens, particularly those containing antimetabolites (e.g., 5-fluorouracil (5-FU), capecitabine), topoisomerase inhibitors (e.g., irinotecan, topotecan), platinum analogs (e.g., oxaliplatin), monoclonal antibodies (e.g., cetuximab, panitumumab), and tyrosine-kinase inhibitors (e.g., sorafenib). During chemotherapy-induced diarrhea (CID), patients may suffer from fatigue, dehydration, electrolyte imbalance, malnutrition, psychological stress, and significant disruption of daily life, as well as abdominal, rectal, and perianal symptoms including pain, excoriation, and discomfort. In addition, severe CID may impair therapy outcomes and increase mortality due to dose delays and reductions and/or interruption.

Severity of CID has been associated with several specific chemotherapeutic regimens, among which regimens involving topoisomerase inhibitors (irinotecan, topotecan) and antimetabolites (5-FU, capecitabine) are associated with a higher incidence of CID than other types [11]. It is estimated that 50%-80% of patients receiving irinotecan and/or 5-FU chemotherapy develop CID due to inflammation and ulceration in the intestine and changes in the intestinal microbiota; if not addressed, CID can become life-threatening, as it may lead to severe dehydration and sepsis. Historically, clinical practice guidelines from the European Society of Medical Oncology (ESMO) and Chinese Society of Clinical Oncology (CSCO) have recommended stratified treatment based on diarrhea grading under the basic care of dietary adjustment and fluid replacement. For grade 1 diarrhea, observation and dietary adjustment are provided. For grade 2 diarrhea, standard antidiarrheal agents (such as loperamide) are administered for management. For grade 3 and 4 diarrhea, the suspected chemotherapeutic drugs should be discontinued immediately, and active management includes intravenous administration of octreotide and antibiotics. Even with these options, many patients still have unmet needs, especially in severe diarrhea. Notably, nutritional adjuvants, which encompass dietary counseling, food supplements, and medical nutrition therapy, may not only address nutritional needs but also alleviate or reverse CID.

Nutritional adjuvants are an important part of supportive care. It includes diet counseling, oral supplements, and medical nutrition therapy. Studies have shown that probiotics administration, traditional herbal medicine supplementation, a Mediterranean Modified Healthy Diet, and avoidance or limitation of spicy, fatty, or dairy products could effectively reduce CID. However, the evidence remains insufficient. Many strategies are hard to follow in daily life, and adherence is often low. In addition, few studies provide a simple and culturally acceptable food-based option for Chinese patients during active chemotherapy.

The concentrated phytodietary compound (CPC) is a food-based supplement, whose ingredients are natural foods beneficial for diarrhea treatment, including taro, carrot, glutinous rice, and rice, all of which are consistent with the omnivorous dietary habits of the Chinese population. This study aims to evaluate CPC as a nutritional adjunct to routine CID treatment.