Context: The most debilitating symptoms during oxaliplatin-based chemotherapy in patients with colorectal cancer (CRC) are neuropathy and fatigue. Inflammation has been suggested to contribute to these symptoms, and the anti-inflammatory agent minocycline is safe and readily available. Objectives: This proof-of-concept study investigated minocycline's capacity to reduce treatment-related neuropathy and fatigue and its impact on inflammatory markers during chemotherapy in a Phase II randomized, double-blind, placebo-controlled clinical trial. Methods: Patients with locally advanced or metastatic CRC who were scheduled for oxaliplatin-based chemotherapy were randomly assigned to receive either minocycline (100 mg twice daily) or placebo over four months from started chemotherapy. Toxicity assessments and blood samples were prospectively collected monthly. The severity of fatigue and numbness/tingling was assessed weekly using the MD Anderson Symptom Inventory. The primary endpoint, area under the curve for numbness/tingling and fatigue over approximately four months, was compared between the two arms. Results: Of 66 evaluable participants, 32 received minocycline and 34 placebo. There was no observed significant symptom reduction on both fatigue and numbness/tingling in either arm, nor was there a difference in levels of serum proinflammatory and anti-inflammatory markers between arms. No Grade 3 adverse events nor disparity mediating effects on intervention were observed. Conclusion: Minocycline treatment is feasible and has a low-toxicity profile. However, with 200 mg/day, it did not reduce numbness/tingling or fatigue nor moderate inflammatory biomarkers from this Phase II randomized study. Our results do not support further exploration of minocycline for fatigue or neuropathy symptom intervention in patients treated for CRC.
- chemotherapy-induced symptoms
- colorectal cancer
- patient-reported outcomes
ASJC Scopus subject areas
- Clinical Neurology
- Anesthesiology and Pain Medicine