Abstract
Purpose: Chemotherapy-induced gastrointestinal (CIGI) toxicity affects the quality of life of patients with colorectal cancer (CRC) and the clinical application of treatment drugs. This review aims to evaluate the efficacy of traditional herbal medicines (HMs) in alleviating symptoms of CIGI toxicity (including nausea and vomiting, anorexia, diarrhea, constipation, oral mucositis, abdominal pain, and abdominal distension), and to explore further individual herb or herbal combinations in alleviating the CIGI toxicity.Methods: Nine electronic databases were screened from 2010 to 2020. Twenty-two randomized controlled trials with a total of 1,995 patients evaluating the complementary efficacy of HMs with chemotherapy compared with chemotherapy-alone were included. Further, sensitivity analyses of orally administered multi-ingredient HM interventions were explored based on the composition of HM interventions.Results: The meta-analysis showed that HM treatment combined with chemotherapy significantly alleviated the overall CIGI toxicity (RR = 0.78 [0.72, 0.84], p < 0.001, I2 = 44%), nausea and vomiting (RR = 0.74 [0.66, 0.82], p < 0.001, I2 = 35%), diarrhea (P = 0.02, RR = 0.64, 95% CI = 0.44–0.93, I2 = 50%), oral mucositis (RR = 0.65 [0.48, 0.88], P = 0.005, I2 = 24%), and abdominal distension (RR = 0.36 [0.18, 0.73], P = 0.004, I2 = 0%). However, no statistically significant effects of HMs were shown in studies with a double-blind design for CIGI toxicity. Based on the ingredients of the HMs, further sensitivity analyses identified five herbs [Glycyrrhiza uralensis Fisch., Atractylodes macrocephala Koidz., Astragalus membranaceus (Fisch.) Bge., Codonopsis pilosula (Franch.) Nannf., and the pericarp of Citrus reticulata Blanco.] that were associated with significant reductions in CIGI toxicity.Conclusion: A statistically significant effect of HMs combined with chemotherapy on alleviating the overall CIGI toxicity, nausea and vomiting, diarrhea, oral mucositis, or abdominal distension is only shown in studies without a double-blind design. Further well-designed, double-blinded, large-scaled randomized controlled trials (RCTs) are warranted to comprehensively evaluate the treatment efficacy. Further clinical research that includes the five herbs with chemotherapy for patients, the safety of the combinations of these herbs, and the potential synergistic effects of these combinations of herbs should be conducted.
Highlights
Colorectal cancer (CRC) is considered the second most frequently diagnosed carcinoma in women and the third in men worldwide
Chemotherapy 5-fluorouracil (FU) has been the backbone of treatment in patients with CRC for more than half a century [2], and the combination of 5-FU with irinotecan and oxaliplatin has become the standard of therapy for patients with metastatic CRC in the late 1990’s [3]
The results demonstrated that the treatment groups significantly reduced CIGI toxicity compared to control groups in studies without a double-blind design, with an effect of 0.50; no statistically significant difference between treatment groups and control groups in studies with a double-blind design was found
Summary
Colorectal cancer (CRC) is considered the second most frequently diagnosed carcinoma in women and the third in men worldwide. Up to 80% of patients with CRC receiving 5-FU based adjuvant therapy develop gastrointestinal (GI) toxicity, which is currently without a widely effective treatment strategy [4, 5]. Other common GI symptoms reported by patients with cancer such as altered taste, anorexia, dysphagia, reflux, regurgitation, borborygmi, bloating, constipation, diarrhea, tenesmus, mucus discharge, steatorrhea, weight loss, etc., are still lacking optimal management [7, 8]. These symptoms often lead to a reduction of therapeutic dose, compromised clinical efficacy of treatment drugs, and impinge on the quality of life of patients. Severe complications of CIGI toxicity such as bacteremia and sepsis interfere with chemotherapy prompting dose reduction and, in profound cases, cessation of therapy
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