ABSTRACT
Background: In a Phase II study RRx-001 was combined with Etoposide platinum (EP) in previously platinum treated SCLC. We correlated expression of the M2 marker, CD206, on HLA-DRlow/- monocytes, a phenotype that correlates with a poor prognosis, with response to RRx-001.
Research design and methods: Patients received 4 mg RRx-001 once weekly until progression followed by the start of EP (etoposide 100 mg/m2 IV on days 1–3 of a 21-day cycle and either cisplatin 80 mg/m2 IV on day 1 or carboplatin AUC 5–6 IV on day 1). Treatment continued until progression or intolerable toxicity. Peripheral blood was collected in Cell Preparation Tubes with sodium citrate from 14 patients for exploratory studies during screening and after therapy on Days 1, 8, and 15. Peripheral blood mononuclear cells (PBMCs) were isolated from blood by centrifugation and multiparameter flow cytometric analysis was performed.
Results: CD206 expression on HLA-DRlow/- monocytes was associated with response to chemotherapy and overall survival.
Conclusion: During treatment with RRx-001, reduced expression of the protumorigenic M2 marker CD206 on peripheral monocytes positively correlated with increased response and survival.
Author contributions
Authors MJL, YT, AY, SL, NA, BO, SC, and JT participated in the design and execution of the study. All authors (MJL, YT, AY, SL, NA, BO, SC, and JT) contributed to the analysis, manuscript drafting, manuscript writing, manuscript editing, and manuscript review.
Acknowledgments
The authors disclose that EpicentRx, Inc. is the clinical trial sponsor.
Declaration of interest
All authors received funds from EpicentRx, Inc. to research RRx-001. Authors BO and SC are employed by EpicentRx, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.