Endogenous Heat-Shock Protein Induction with or Without Radiofrequency Ablation or Cryoablation in Patients with Stage IV Melanoma.

Abstract

LESSONS LEARNED:

Percutaneous thermal ablation combined with in situ granulocyte-macrophage colony-stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen.

BACKGROUND:

Melanoma tumor-derived heat-shock proteins (HSPs) and HSP-peptide complexes can elicit protective antitumor responses. The granulocyte-macrophage colony-stimulating factor (GM-CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs). On this basis, we designed a pilot study of percutaneous thermal ablation as a means to induce heat-shock protein vaccination plus GM-CSF to determine safety and preliminary antitumor activity of this combination.

MATERIALS AND METHODS:

This study was designed to assess overall safety of percutaneous ablation combined with GM-CSF for unresectable, metastatic melanoma including uveal and mucosal types. All patients received heat-shock therapy (42°C for 30 minutes), then received one of three treatments: (a) intralesional GM-CSF (500 mcg standard dose); (b) radiofrequency ablation (RFA) + GM-CSF; or (c) cryoablation plus GM-CSF. The primary endpoint of the study was the induction of endogenous HSP70 and melanoma-specific cytotoxic T lymphocytes (CTL).

RESULTS:

Nine patients (three per study arm) were enrolled. No dose-limiting toxicity was observed as specified per protocol. All patients developed progressive disease and went on to receive alternative therapy. Median overall survival (OS) was 8.2 months (95% confidence interval [CI] 2-17.2). The study was not powered to detect a difference in clinical outcome among treatment groups.

CONCLUSION:

Percutaneous thermal ablation plus GM-CSF was well tolerated, technically feasible, and demonstrated an acceptable adverse event profile comparable to conventional RFA and cryoablation. While HSP70 was induced following therapy, the degree of HSP70 elevation was not associated with clinical outcome or induced CTL responses. While percutaneous thermal ablation plus GM-CSF combinations including checkpoint inhibitors could be considered in future studies, the use of GM-CSF remains experimental and for use in the context of clinical trials.

• Authors: Evidio Domingo-Musibay, James M Heun, Wendy K Nevala, Matthew Callstrom, Thomas Atwell, Evanthia Galanis, Lori A Erickson, Svetomir N Markovic
• Journal: The oncologist (Oncologist) Vol. 22 Issue 9 Pg. 1026-e93 (09 2017) ISSN: 1549-490X [Electronic] England
• PMID: 28679643 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © AlphaMedPress; the data published online to support this summary is the property of the authors.

Chemical References

• HSP70 Heat-Shock Proteins
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Aged
• Aged, 80 and over
• Combined Modality Therapy
• Cryosurgery (adverse effects, methods)
• Feasibility Studies
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
• HSP70 Heat-Shock Proteins (metabolism)
• Humans
• Hyperthermia, Induced (adverse effects, methods)
• Immunotherapy (adverse effects, methods)
• Injections, Intralesional
• Kaplan-Meier Estimate
• Male
• Melanoma (immunology, mortality, pathology, therapy)
• Middle Aged
• Neoplasm Staging
• Pilot Projects
• Skin Neoplasms (immunology, mortality, pathology, therapy)
• T-Lymphocytes, Cytotoxic (drug effects, immunology, radiation effects)
• Treatment Outcome