TABLE 3.
Topics For Consideration During the Discussion Session
| Guided discussion topics |
|---|
|
|
| Preclinical model considerations |
| Animal model and strain selection (different efficacy) |
| Testing human vs. rodent/NHP growth factor equivalents |
| Understanding mechanism of action |
| Supportive care for models (G-/GM-CSF as standard of care) |
| Dose rates – very low or very high – how do growth factors perform in these scenarios? |
| Efficacy of growth factors with mixed field irradiation exposures |
| Heterogeneity of exposure. TBI/shielded/marrow sparing and “leakage” of radiation under shield |
| Science of cytokines |
| Low-dose vs. high-dose radiation exposures |
| Thresholds for bone marrow injury, after what radiation exposure are treatments more effective? |
| Efficacy of growth factors in radiation combined injuries |
| Doses administered (high-dose vs. low-dose use of growth factors; less drug/dose or fewer doses?) |
| Timing of administration |
| Many factors are induced by radiation; supplement endogenous production at an earlier time point to reduce cell stress? |
| Optimal clinical use |
| Are some growth factors more efficacious than others? |
| Possible negative late impacts of early growth factor use (e.g., late lung effects) |
| Some factors may be contraindicated |
| What other growth factors in clinical use can be repurposed? |
| Availability of clinical data |
| Confounders (chemotherapy, fractionated radiation exposure) |
| Operational considerations |
| Use in special populations |
| Impact of supportive care on growth factor efficacy |
| Triage guidelines: scarce resources decisions, ethics involved |
| Off-label use |
| Stockpiling constraints |
| Timing and availability |
| Production capacity and timelines |
| Storage or vendor managed inventory |
| Regulatory considerations |
| Importance of primary clinical indication |
| Easier to repurpose licensed/approved products? |
| Challenges for animal rule approval |
| Poly-pharmacy considerations |
| Combination strategies to enhance effect of growth factors |
| G-/GM-CSF as standard-of-care, are approaches additive? Do they interfere? |
| On the horizon |
| Novel factors under study: What are the next “low hanging fruits”? |
| Other factors to address specific organ systems (e.g., GI, lung, renal, cardiac, vascular, central nervous system, etc.) |
| Enhancing growth factors [e.g., extending half-life (pegylation) and/or improving potency] |