20% of patients resistant to secondline
chemotherapy for advanced non-
small-cell lung cancer (NSCLC) responded
to a combination of
cetuximab (Erbitux) and docetaxel
(Taxotere) in a phase II clinical trial.
Edward S. Kim, MD, assistant professor
of medicine of the Department
of Thoracic Oncology, Head and Neck
Medical Oncology, at the University
of Texas M. D. Anderson Cancer Center,
Houston, reported a 28% response
rate in 47 evaluable patients. The rate
was to 22.2% when investigators tallied
all 54 patients, including three
who died of unrelated adverse events
(ASCO abstract 2581).
The only approved chemotherapy
for second-line NSCLC is docetaxel,
Dr. Kim noted. Although docetaxel
has been shown to produce a response
rate as high as 21%, he told ONI that
15% or less is more typical for platinum-
refractory NSCLC patients.
Concerning the cetuximab plus
docetaxel combination, Dr. Kim said,
"In a limited study, there is encouraging
activity, and it warrants further
investigation in a randomized setting.
Is this going to cure cancer? Probably
not. Could it help people live longer?
Continued support of the investigation
is uncertain, Dr. Kim noted.
The issue is not scientific merit, but
allocating limited resources, he said,
expressing hope that funds could be
found for a second randomized phase
II study if a full phase III trial were not
possible at this time.
Phase II Results
A monoclonal antibody, cetuximab
targets the HER1/epidermal growth
factor receptor (HER1/EGFR), which
is expressed in lung cancer and many
other solid tumors. Patients in the
phase II trial received 400 mg/m2 of
cetuximab intravenously the first week
and 250 mg/m2 every week thereafter.
They were given 75 mg/m2 of docetaxel
intravenously every 3 weeks.
One patient had a complete response,
and 11 had partial responses.
Another 18 had progressive disease,
and 7 were not evaluable.
Median progression-free survival
was reported at 2.6 months for the full
cohort; median overall survival was
7.5 months. The median time to disease
progression was 89 days. The
median number of cycles was 4 with a
range of 1 to 30 with several patients
still on study. These data are not final,
however, as five patients are still on
Dr. Kim added that the results are
particularly encouraging in light of
the poor condition of the study population.
The trial not only restricted
enrollment to EGFR-positive patients
who were actively failing chemotherapy,
but it also insisted that patients
have had disease recurrence within 3
months of their last chemotherapy.
"We wanted to focus on those patients
who were actively progressing on chemotherapy,"
Dr. Kim said, adding,
"We were dealing with a very sick population."
He cited one man who died of an
unrelated adverse event between cycles
three and four. Although the in-
vestigators had recorded major shrinkage
of the man's tumor, Dr. Kim said
they could not call it a confirmed response.
Four patients discontinued because
of allergic reactions but the regimen
was reported to be well tolerated with
minimal toxicity. Infection in 21% of
patients, fatigue in 21%, and rash in
19% were the most common grade 3
toxicities. One grade 4 diarrhea and
two cases of grade 4 pulmonary embolus
Cetuximab did not appear to interact
with docetaxel in pharmokinetic