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

CONTEXT: Although 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. OBJECTIVES: To investigate the efficacy of minocycline, an anti-inflammatory agent, for symptom reduction in patients with advanced PC. METHODS: We 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. 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 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. 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 because of rapid disease progression impacted the study significantly.

Quality of life impact of EUS in patients at risk for developing pancreatic cancer.

BACKGROUND AND OBJECTIVES: The current knowledge about the psychological impact of pancreatic cancer (PC) screening is limited. We aimed to assess the changes in quality of life (QOL) and level of distress after undergoing EUS in individuals with pancreatic cystic lesions (PCLs) and in patients at high risk for PC based on genetic and familial factors. METHODS: Eighty patients with PCL and/or increased genetic or familial risk for PC who had undergone EUS were contacted. Fifty percent of those patients successfully completed the brief profile of mood states (POMS) and the linear analog scale assessment (LASA) QOL questionnaires to evaluate their pre/post-EUS overall QOL. The effect size (ES) method was used to assess clinically meaningful changes in the scores. RESULTS: There was a significant difference in patients' overall QOL scores before and after the EUS procedure (LASA, mean difference 0.73, standard deviation (SD) 1.76, ES 0.58, P < 0.01; brief POMS, mean difference -5.46, SD -6.72, ES 0.81, P < 0.01). CONCLUSIONS: QOL of patients with PCL or increased risk factors for PC is significantly improved after a EUS/EUS-guided fine-needle aspiration (FNA) negative for malignancy.

Minocycline Reduces Chemoradiation-Related Symptom Burden in Patients with Non-Small Cell Lung Cancer: A Phase 2 Randomized Trial.

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 antiinflammatory properties. We conducted a phase 2 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 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 with placebo group during the 12-week trial period (area under the curve = 31.2 ± 14.2 vs 45.0 ± 20.9, P = .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 < .05). CONCLUSIONS: 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.

Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy.

CONTEXT: Intensity-modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT), and proton-beam therapy (PBT) are chemoradiotherapy modalities for treating locally advanced non-small-cell lung cancer. Although therapy is carefully planned to maximize treatment benefit while minimizing risk for adverse side effects, most patients develop radiation-induced symptom burden. OBJECTIVES: To demonstrate the MD Anderson Symptom Inventory's ability to detect fine differences in symptom development among these modalities. METHODS: This was a longitudinal observational study. Patients with unresectable primary or recurrent non-small-cell lung cancer (n = 82) underwent 3DCRT, IMRT, or PBT. Patients rated MD Anderson Symptom Inventory symptoms weekly for up to 12 weeks. We used mixed-effect modeling to estimate development of symptoms and functional interference. RESULTS: The PBT group received a significantly higher radiation target dose than did the IMRT and 3DCRT groups (P < 0.001). Fatigue was the most severe symptom over time for all groups. Controlling for patient and clinical factors (age, sex, race, cancer stage, performance status, body mass index, previous cancer therapy, total radiation dose), we found that pain, as a major esophagitis-related symptom, increased more during therapy (P = 0.019) and decreased more after (P = 0.013) therapy in the 3DCRT and IMRT groups than in the PBT group. Compared with the PBT group, the 3DCRT and IMRT groups reported greater decrease in systemic symptoms (fatigue, drowsiness, lack of appetite, disturbed sleep) after therapy (P = 0.016). CONCLUSION: Patients receiving PBT reported significantly less severe symptoms than did patients receiving IMRT or 3DCRT. These results should be confirmed in a randomized study with comparable tumor burden among therapies.