ST. LOUIS, MISSOURI-
Gefitinib (ZD1839, Iressa) was not active
against malignant mesothelioma
in a phase II study testing the novel
agent in 43 patients with unresectable
Investigator Ramaswamy Govindan
MD, assistant professor, Division
of Medical Oncology, Washington
University in St. Louis, told ONI that
results from the multicenter Cancer
and Leukemia Group B investigation
were disappointing (ASCO abstract
2535). There were no complete responses
and only one patient had a
partial response. While 21 patients had
stable disease, 16 progressed and 5
died within 2 months of registering
for the study. Median failure-free survival
was 1.7 months, and median survival
was 6.8 months, on the low end
for malignant mesothelioma.
Dr. Govindan said that the group
undertook the study because gefitinib
had been active against malignant
mesothelioma cell lines in vitro. The
agent is an HER1/epidermal growth
factor receptor (HER1/EGFR) tyrosine
kinase inhibitor, and EGFR amplification
is a common feature of the
Of 28 patients in the study for
whom immunohistochemistry was
available, all but one showed EGFR
expression. EGFR levels for 10 patients
were at 2+, and 17 reached 3+,
an echelon Dr. Govindan characterized
as "an intense expression." Yet he
reported, "EGFR expression did not
seem to correlate with any benefit."
All patients in the study had measurable
disease less than 4 months after
radiation therapy. None had prior
cytotoxic therapy or another treatment
targeting EGFR. With only four females,
the population was overwhelmingly
male. The group's median age
was 72, as all but seven patients were
age 60 or older. Epithelial disease was
diagnosed in 34 patients, and all cases
but 1 were pleural in origin.
The patients received a fixed oral
dose of 500 mg of gefitinib once a day
in 21-day cycles that continued as long
as the patient did not progress or have
to discontinue because of adverse
events. The treatment was generally
well tolerated. Diarrhea and nausea
were the most common adverse events.
Only two patients had a grade 3 rash,
a common side effect that other studies
have suggested might be a biomarker
for response to EGFR agents.
Might Some Patients Benefit?
Dr. Govindan said the investigators
plan to analyze the data to see
whether a subset of patients might be
more likely to respond to gefitinib.
"[For the overall] group it's not active,
but we still don't know which patients
are likely to benefit," he said.
Commenting on various lung cancer
trials, Alex Adjei, MD, PhD, of the
Mayo Clinic in Rochester, Minnesota,
noted, "Single-agent Iressa unfortunately
has no role [in malignant mesothelioma]."
He said it might still be
worth investigating as a maintenance
therapy after other treatments.