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

Abstract

ContextAlthough it is well known that patients with advanced pancreatic cancer (PC) experience significant symptom burden, few strategies for effective symptom intervention are available for them. ObjectivesTo investigate the efficacy of minocycline, an anti-inflammatory agent, for symptom reduction in patients with advanced PC. MethodsWe conducted Phase II, randomized, and placebo-controlled trial to obtain preliminary estimates of the effects on symptom reduction with 100 mg of 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 eight-week trial using the MD Anderson Symptom Inventory (MDASI) module in patients with gastrointestinal cancer. The primary outcome measure was the area under the curve values of the five most severe symptoms in the two arms. ResultsOf 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 area under the curve values over time between the study arms were found for the composite MDASI score or single-item scores of the five most severe MDASI items. No treatment-related deaths were reported, and no Grade 3–4 toxicities were observed. ConclusionMinocycline 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 because of rapid disease progression impacted the study significantly.