Integrative Herbal Medicine for Chemotherapy-Induced Peripheral Neuropathy and Hand-Foot Syndrome in Colorectal Cancer: A Systematic Review and Meta-Analysis

Objectives: To assess the clinical evidence for integrative herbal medicine therapy in the management of chemotherapy-induced peripheral neuropathy (CIPN) and hand-foot syndrome (HFS) resulting from treatments for colorectal cancer (CRC). Design: Randomized controlled trials (RCTs) were identified from major English and Chinese databases. Participants had been diagnosed with CRC by pathology and had received or were undergoing chemotherapy. Interventions included herbal medicines administered orally or topically. Controls were placebo, supportive care or conventional chemotherapy for CRC. Methods followed the Cochrane handbook. Meta-analyses were grouped by study design, outcome measure, severity, and chemotherapy. Random-effects models with 95% confidence intervals were used. Heterogeneity was assessed as I-2. Results: Sixty-three RCTs (4286 participants) were included. Five used a placebo in the control groups. Fifty-eight studies tested oral herbal medicine, and 5 tested topical herbal medicine. Data were available for CIPN (60 studies) and HFS (12 studies). Fifty-seven studies combined orally administered herbal medicine with chemotherapy compared with the same chemotherapy. For CIPN, 33 studies used World Health Organization (WHO) criteria, 7 used Levi's criteria, and 10 used the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). These were analyzed separately. For grades III + IV CIPN, there was a significant reduction in the integrative groups for WHO (relative risk [RR] 0.42 [0.23, 0.77], I-2 = 0%) and Levi's (RR 0.28 [0.11, 0.69], I-2 = 0%) but not NCI-CTCAE (RR 0.65 [0.37, 1.13], I-2 = 26.4%). Hand and foot baths showed no differences for Levi's grades III + IV CIPN but a significant reduction in all grades (RR 0.69 [0.50, 0.95], I-2 = 68.8%). For HFS (all grades) there was a significant reduction in the integrative groups for WHO (RR 0.62 [0.41, 0.96], I-2 = 22%) but not for NCI-CTCAE (RR 0.93 [0.55, 1.55], I-2 = 75.7%). Sensitivity analyses explored sources of heterogeneity. Conclusions: Integrative herbal therapy appeared to reduce CIPN and HFS in people receiving chemotherapy for CRC. However, the strength of the evidence was limited by lack of blinding in most studies, potential for bias, and relatively short study durations.