Mucositis is a common, costly and unpleasant side effect of
cancer chemotherapy and
radiotherapy.
Velafermin (FGF-20) has shown the potential to reduce these side effects.
Irinotecan is a chemotherapeutic agent which is commonly used in solid
tumors, and causes GI
mucositis manifested by severe
diarrhea. Therefore the primary aim of this study was to investigate whether
velafermin reduces the GI
mucositis induced by
irinotecan. The secondary aim was to test varying schedules of administration of
velafermin. Groups of
tumor-bearing DA rats (6 per group) were treated with varying doses (4, 8 or 16 mg/kg) of
velafermin intraperitoneally either prior to, prior to and during, or after
chemotherapy treatment. Rats received a single dose of 200 mg/kg
irinotecan intraperitoneally. Rats were monitored closely for the incidence and severity of
diarrhea and mortality before being killed 192 h following treatment. Mortality,
diarrhea and histopathology were assessed throughout the gastrointestinal tract. Severe or moderate
diarrhea occurred in approximately 40% of rats treated with
irinotecan alone. This was associated with a 50% mortality rate 96 h following
chemotherapy.
Velafermin administered at 16 mg/kg prior to
irinotecan improved gastrointestinal
mucositis as measured by reduced
diarrhea and mortality following
irinotecan chemotherapy in the DA rat. Rats that received
velafermin prior to, or prior to and during
irinotecan treatment did develop severe or moderate
diarrhea, however it occurred later, in fewer rats and was not associated with mortality. Other dosing regimens were not as effective. This has important implications for the use of
velafermin in GI
mucositis in humans, and should be further studied.