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

Abstract

Using a low toxic agent that potentially with anti-inflammatory proprieties, minocycline, we conducted Phase II randomized placebo controlled trial and observed positive effect of reducing fatigue and other symptoms in patients undergoing CRT for NSCLC.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, doubleblinded, 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 (AE2 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 þ 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 Z 31.2 AE 14.2 vs 45.0 AE 20.9, P Z .011), with a large effect size (Cohen's d Z 0.77). Pain (Cohen's d Z 0.54) and shortness of breath (Cohen's d Z 0.55) were also significantly reduced in the minocycline group (all P < .05).

Minocycline for Controlling Neuropathic Pain: A Systematic Narrative Review of Studies in Humans

“…of Patients (Minocycline:Placebo) Minocycline Dose Duration Results 1 Pachman 24 2017 CIN RCT 45 (22:23) 100 mg twice daily 12 weeks During chemotherapy, less pain (10-item questionnaire) and less use of opioids in the minocycline group. 2 Wang 28 2019 CIN RCT 66 (32:34) 100 mg twice daily 4 months On MDASI, no significant improvement in fatigue and neuropathic pain 3 Wang 29 2020 CIN RCT 40 (19:21) 100 mg twice daily 6–7 weeks On MDASI, pain, fatigue, and shortness of breath were significantly reduced in the minocycline group 4 Martinez 22 2013 Lumbar radicular pain RCT 85 (43:42) 100 mg twice daily 8 days On NRS, at rest, 2.3 reduction in score in the minocycline group vs 1.7 reduction in the placebo group. On movement, 3.4 reduction in score in the minocycline group vs 2.5 reduction in the placebo group.…”

“…Among the studies evaluating the pain-reducing effects on chemotherapy-induced neuropathic pain, two studies showed a positive effect, 24 , 29 and the other 28 presented negative results. Pachman et al 24 performed an RCT involving 45 patients with breast cancer receiving weekly paclitaxel chemotherapy.…”

“…The patients in the minocycline group reported less pain and less use of opioid pain medication than the placebo group. Wang et al 29 evaluated minocycline for controlling chemoradiation-related symptoms. They recruited 40 patients with non-small cell lung cancer who were scheduled to receive chemoradiation treatment.…”

“…[21][22][23][24][25][26][27][28][29] In these selected studies, minocycline was administered in a total of 232 cases. Among the included studies (Table 1), the effectiveness of minocycline in treating chemotherapy-induced neuropathic pain was evaluated in three studies 24,28,29 and lumbar radicular pain in two studies. 22,27 Its effectiveness was also evaluated in diabetic neuropathy, 26 leprosy, 23 and carpal tunnel syndrome.…”

Cellular and Molecular Aspects of Anti-Melanoma Effect of Minocycline—A Study of Cytotoxicity and Apoptosis on Human Melanotic Melanoma Cells

“…Investigations of minocycline include its potential application in cancer treatment. Some studies show that the drug reduces treatment-related symptoms, such as fatigue and burden in patients with non-small cell lung cancer [ 36 ] or erlotinib-related acneiform rash and xerosis in patients with advanced pancreatic cancer [ 37 ]. Moreover, there is evidence that minocycline overcomes resistance to topoisomerase inhibition attenuating the efficacy of irinotecan in peritoneal carcinomatosis [ 38 ].…”