Effects of the hematopoietic growth factors GM-CSF, IL-3, and IL-6 on human tumor colony-forming units taken directly from patients.
BACKGROUND
One concern regarding the use of hematopoietic growth factors (e.g., GM-CSF, IL-3, and IL-6) to accelerate hematologic recovery after treatment of solid tumors with high doses of chemotherapy is that these factors may stimulate tumor growth.


METHODS
We tested the effects of GM-CSF, IL-3 or IL-6 (continuous exposure to 1, 10, and 100 ng/ml of each cytokine) on tumor cells taken directly from patients with solid tumors using the human tumor cloning assay. The range of concentrations of the cytokines used in our study included the concentrations that appear to be clinically relevant.


RESULTS
Of the evaluable samples, stimulation of tumor growth was noted in 0/16 exposed to GM-CSF, in 3/72 (4%) exposed to IL-3, and in 1/65 (2%) exposed to IL-6. Inhibition of tumor proliferation was noted in no sample exposed to GM-CSF, in 7 (10%) exposed to IL-3 and in 7 (10%) exposed to IL-6.


CONCLUSIONS
The use of GM-CSF, IL-3 or IL-6 to reduce myelosuppression after high dose chemotherapy appears unlikely to result in stimulation of the growth of the most common solid tumors. It is also unlikely that either IL-3 and IL-6 alone will be useful as antitumor agents against solid tumors.
Izquierdo
M A
MA
Institute for Drug Development, San Antonio, TX, USA.
Degen
D
D
Myers
L
L
Levitt
D J
DJ
Von Hoff
D D
DD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D007377:Interleukin-3; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor