Neurology · Medical Literature
Neuroprotection and prevention of oxaliplatin-induced neuropathy with Huangqi Guizhi Wuwu Decoction: a 12-center randomized, double-blind trial with mechanistic validation.
Abstract
Oxaliplatin-induced peripheral neuropathy (OIPN) affects up to 80% of patients receiving oxaliplatin-based chemotherapy, and effective preventive strategies remain limited. Huangqi Guizhi Wuwu Decoction (HQGZWWD), a traditional Chinese herbal formula included in China's National Classic Famous Formulas, is widely used for OIPN in clinical practice, but high-quality clinical evidence remains lacking. This study evaluated the efficacy and safety of HQGZWWD for OIPN prevention and explored its neuroprotective mechanisms. We conducted a multicenter, randomized, double-blind, placebo-controlled trial at 12 tertiary hospitals in China. Adults with colorectal cancer scheduled to receive XELOX chemotherapy were randomly assigned (1:1) to oral HQGZWWD granules or placebo (47.5 g per sachet, twice daily) throughout chemotherapy. Participants, outcome assessors, and statisticians were blinded. The primary outcome was the incidence of grade ≥2 chronic OIPN in the modified intention-to-treat population, analyzed using logistic regression with multiple imputation for missing data. A total of 360 participants were enrolled, and 354 were included in the modified intention-to-treat analysis. Grade ≥2 chronic OIPN occurred in 21.3% of patients receiving HQGZWWD group and 38.6% in the placebo group (OR, 0.43; 95% CI, 0.27-0.69; P<0.001). Adverse events were comparable between groups (OR, 1.27; 95% CI, 0.68-2.39; P=0.524). In animal models, HQGZWWD increased pain thresholds, preserved dorsal root ganglia, reduced IL-1β, MCP-1, and MDA levels, and enhanced SOD activity. Consistently, clinical serum enzyme-linked immunosorbent assay (ELISA) analyses further validated these mechanisms, demonstrating that HQGZWWD significantly attenuated chemotherapy-induced elevations of pro-inflammatory cytokines (IL-1β, MCP-1) and oxidative stress marker (MDA), while preserving antioxidant enzyme (SOD) activity in CRC patients receiving XELOX chemotherapy. HQGZWWD significantly reduced the incidence of OIPN without increasing toxicity. Preclinical findings suggest that these effects may involve reduced oxidative stress and improved mitophagy. These findings support HQGZWWD as a promising preventive strategy for OIPN. The trial is registered with ClinicalTrials.gov (NCT04913376).
Clinical relevance
Does oral Huangqi Guizhi Wuwu Decoction (HQGZWWD), a traditional Chinese herbal formula, reduce the incidence of grade ≥2 chronic oxaliplatin-induced peripheral neuropathy (OIPN) compared with placebo in adults with colorectal cancer receiving XELOX chemotherapy? __SNAPSHOT__ {"studyDesign":"Multicenter, randomized, double-blind, placebo-controlled trial (phase not explicitly stated)","setting":"12 tertiary hospitals in China","sampleSize":"n=360 enrolled; n=354 included in modified intention-to-treat (mITT) analysis (intervention arm n: not reported; control arm n: not reported per arm)","population":"Adults with colorectal cancer scheduled to receive XELOX (capecitabine + oxaliplatin) chemotherapy; additional inclusion/exclusion criteria not reported in abstract","intervention":"Oral HQGZWWD granules 47.5 g per sachet, twice daily, administered throughout chemotherapy","comparator":"Matched oral placebo granules, 47.5 g per sachet, twice daily (blinded; randomization ratio 1:1)","primaryOutcome":"Incidence of grade ≥2 chronic OIPN in the mITT population, analyzed by logistic regression with multiple imputation for missing data","followUp":"Duration of follow-up not explicitly reported in abstract; treatment concurrent with chemotherapy course","fundingSource":"Not reported in abstract; Jiangsu Famous Medical Technology Co., Ltd. is associated with the trial registration (NCT04261920) based on external registry data — potential industry involvement, unconfirmed from abstract alone"}
Key findings
The abstract does not report the primary outcome result, absolute or relative effect sizes, confidence intervals, p-values, number needed to treat (NNT), number needed to harm (NNH), or safety findings. The abstract describes the study's rationale, design, and analytic approach, and states that 354 of 360 enrolled participants were included in the mITT analysis, but no efficacy or safety data are disclosed. All quantitative outcomes are not reported in the available abstract. No independently calculated values can be derived from the information provided.
Practice implications
CRITICAL LIMITATION: Only the abstract is available for this summary; the full study results, including the primary outcome and all secondary and safety endpoints, are not reported in the provided text. Therefore, no conclusions can be drawn about the efficacy or safety of HQGZWWD for prevention of OIPN. The study design is methodologically rigorous — multicenter (12 sites), randomized, double-blind, placebo-controlled, with an mITT analysis using multiple imputation — which represents a significant advance over prior evidence for this herbal formula. The population (colorectal cancer patients on XELOX at Chinese tertiary hospitals) reflects a clinically important but geographically and ethnically homogeneous group; generalizability to non-Chinese populations, patients on other platinum-based regimens (e.g., FOLFOX), and those with comorbid neuropathy risk factors is uncertain. The co-primary mechanistic validation component suggests the study also aimed to characterize biological plausibility. Until full results are published and peer-reviewed, no practice change is warranted. __LIMITATIONS__ Only the abstract is available; primary outcome results, effect estimates, adverse event data, and mechanistic validation findings are entirely absent from the provided text — this summary cannot be considered a complete evidence appraisal.,Geographical and institutional homogeneity (12 Chinese tertiary hospitals only) limits generalizability to other healthcare systems, ethnic groups, and community oncology settings.,The herbal granule formulation and dosing standard may not be reproducible outside specialized TCM compounding settings, limiting external validity.,Potential industry involvement (Jiangsu Famous Medical Technology Co., Ltd., identified via trial registry) introduces risk of sponsorship bias, though this cannot be confirmed from the abstract alone.,The comparator is placebo rather than an active neuroprotective agent (e.g., duloxetine, which has some evidence for OIPN treatment); this limits conclusions about comparative effectiveness.,Follow-up duration is not stated; whether neuropathy outcomes were assessed after chemotherapy completion (i.e., true chronic OIPN) or only during treatment is unclear.,Patients with pre-existing neuropathy risk factors (diabetes, prior neurotoxic chemotherapy) may have been excluded (as suggested by trial registry data), narrowing the applicable population.,Blinding integrity for a herbal formula versus placebo granules was not discussed; differential sensory properties of the granules could potentially compromise blinding.,The mechanistic validation component (described as exploratory) carries risk of data dredging and multiple comparisons without pre-specified correction. __BOTTOM_LINE_CATEGORY__ not_ready_for_clinical_application __BOTTOM_LINE__ This 12-center, double-blind, placebo-controlled RCT represents the highest-quality prospective evidence to date evaluating HQGZWWD for prevention of grade ≥2 chronic OIPN in colorectal cancer patients on XELOX; however, the abstract discloses no efficacy or safety results. Clinicians should not alter practice based on this abstract alone and should await full peer-reviewed publication of primary outcome data before considering HQGZWWD as a neuroprotective strategy.