Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non–small Cell Lung Cancer: A Phase II Randomized Trial

Abstract Purpose In patients with non–small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with anti-inflammatory properties. We conducted a phase II randomized, double-blinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. Methods and Materials Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (±2 days) area under the curve (AUC) for symptom burden, which was compared between treatment groups. Results Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3+ adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared to placebo group during the 12-weeks trial period (AUC=31.2±14.2 vs. 45.0±20.9, P=0.011), with a large effect size (Cohen’s d=0.77). Pain (Cohen’s d=0.54) and shortness of breath (Cohen’s d=0.55) were also significantly reduced in the minocycline group (all P Conclusion Minocycline during CRT for NSCLC was feasible, had a low toxicity profile, and yielded a clinically and statistically significant positive signal in reducing symptom burden related to NSCLC and CRT. This study is a proof of concept so a larger trial in CRT patients is warranted.