LOS ANGELES-In patients who
have exhausted all other treatment
options for metastatic colorectal cancer,
cetuximab (Erbitux) is well tolerated
and active. This is the conclusion
drawn from one of the largest trials to
date of single-agent monoclonal antibody
therapy in chemotherapy-refractory
metastatic colorectal cancer (abstract
A response rate of about 12% was
reported for cetuximab initiated in
nearly 350 patients in whom regimens
with irinotecan (CPT-11, Camptosar)
and with oxaliplatin (Eloxatin) had
failed. Median survival time approached
7 months (abstract 3510).
The study report, "demonstrates
convincingly that this agent has activity
in heavily pretreated patients and is
well tolerated," reported Heinz-Josef
Lenz, MD, director of gastrointestinal
oncology at USC/Norris Comprehensive
Cancer Center, Los Angeles.
"A response rate of over 10% is
impressive: compare to that the response
rates with FOLFOX [fluorouracil
and FOLFIRI [5-FU/folinic acid/irinotecan]
in second-line chemotherapy,"
Dr. Lenz stated.
Interestingly, response was con-
firmed in one of nine patients whose
tumors had stained negative for epidermal
growth factor receptor (EGFR).
This was notable because the activity
of cetuximab is thought to be related
to its activity against EGFR. As a result
of this finding, which included one
confirmed and one unconfirmed response,
investigators launched a new
trial to evaluate the efficacy of cetuximab
in EGFR-negative tumors.
Impressive Response Rate
For the study, a total of 346 patients
with metastatic colorectal cancer
received cetuximab at an initial
dose of 400 mg/m2, followed by weekly
treatments at a dose of 250 mg/m2.
The patients had undergone a median
of four prior regimens containing
irinotecan or oxaliplatin. All but nine
patients had tumors with immunohistochemical
evidence of EGFR expression.
The objective response rate was
12.1% (42 patients, all partial responses)
by investigator assessment and
11.6% (40 patients) by independent
review committee (IRC) assessment
(see Table 1). Another 31.8% (110
patients) had stable disease by IRC
assessment. The median overall survival
time was 6.7 months.
These results were consistent with
prior studies of cetuximab monotherapy
in metastatic colorectal cancer,
according to the investigators.
Safe, Well Tolerated
The most adverse event was an
acneiform rash characteristic of
with an EGFR-targeted agent.
The rash was seen in 90% of patients
treated, but in only 12% of cases was
the rash grade 3/4 in severity, including
2% grade 4. Infusion reactions,
almost all grade 1/2, were noted in
17% of patients. Other reported adverse
events included diarrhea, fatigue
or malaise, nausea and vomiting, and
"This is an effective agent in refractory
patients, and it is safe and well
tolerated," Dr. Lenz said.
Further investigation is warranted
in "EGFR nondetectable" tumors, investigators
added. Of the nine patients
with tumors in which EGFR could not
be detected, four had disease control,
including the one confirmed response
and three patients rated as having stable
disease. In addition, eight of the
nine patients had the characteristic