Colorectal cancers (CRC) express the
epidermal growth factor receptor (
EGF-R), a type I transmembrane receptor with
tyrosine kinase activity.
EGF-R signaling inhibition is a promising target for
cancer therapy.
ZD1839 (
Iressa, AstraZeneca) and
OSI-774 (
Tarceva, Roche) are small molecular weight molecules with selective and reversible
tyrosine kinase inhibition properties directed to
EGF-R. Orally administered, these molecules induce sustained
tumor stabilizations in previously treated metastatic CRC patients. The most frequent treatment-related toxicities are
fatigue,
diarrhea and
acne-like follicular
rash. The addition in the clinic of
5-FU, lOHP or
CPT-11 to
ZD1839 or
OSI-774 does not seem to increase the own toxicity of each
cytotoxic agents.
Cetuximab (
Erbitux, Merck) is an intravenously administered humanized
monoclonal antibody which bind with high affinity with the extracellular domain of the
EGF-R. The most frequent treatment-related toxicities are
diarrhea,
fatigue,
nausea and cutaneous toxicity (allergic or
acne-like follicular rashes,
folliculitis). Most, if not all of these adverse events are mild. Partial responses were observed with
cetuximab either alone (RR: 10%) or in combination with
CPT-11 (RR: 22%) in patients with
CPT-11 refractory advanced CRC which expressed
EGF-R. The combination of
cetuximab to
folinic acid,
5-FU and
CPT-11 seems tolerable at the cost of a slight increase of severe
diarrhea and
neutropenia. Finally, the promising activity of these
EGF-R inhibitors has to be confirmed throughout randomized studies.