A Randomized, Placebo-Controlled, Double-Blind Study of Minocycline for Reducing the Symptom Burden Experienced by Patients with Advanced Pancreatic Cancer

Abstract Context Although it’s well known that patients with advanced pancreatic cancer (PC) experience significant symptom burden, few strategies for effective symptom intervention are available for them. Objective To investigate the efficacy of minocycline, an anti-inflammatory agent, for symptom reduction in advanced PC patients. Methods We conducted a phase II, randomized, placebo-controlled trial to obtain preliminary estimates of the effects on symptom reduction with 100 mg minocycline or placebo given twice a day. Eligible patients had diagnosed advanced PC and were scheduled for standard chemotherapy. Patient-reported symptoms were measured weekly during the 8-week trial using the MD Anderson Symptom Inventory module in patients with gastrointestinal cancer (MDASI-GI). The primary outcome measure was the area under the curve (AUC) values of the 5 most-severe symptoms in the 2 arms. Results Of the 44 patients recruited, 31 (71%) were evaluable for the primary efficacy analysis, with 18 received minocycline and 13 placebo. Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were the most-severe symptoms reported by both groups. No significant differences in AUC values over time between the study arms were found for the composite MDASI score or single-item scores of the 5 most-severe MDASI items. No treatment-related deaths were reported, and no grade 3-4 toxicities were observed. Conclusion Minocycline is safe for use in patients receiving treatment for PC. There is no observed symptom reduction with minocycline on the major symptom burden associated with advanced PC compared with placebo. Attrition due to rapid disease progression impacted the study significantly.