BIRMINGHAM, United KingdomEarly trials of Iressa (ZD1839), a
novel anticancer compound, reveal encouraging antitumor activity and
disease stabilization, according to reports presented at the ASCO meeting.
Iressa blocks a pathway implicated in a variety of solid tumors. The
pathway is triggered by an epidermal growth factor that binds to an
epidermal growth factor receptor (EGFr) that sends signals within the
cell via tyrosine kinase.
Blocking the tyrosine kinase switches off the signals from the EGFr,
potentially stopping tumor growth, David Ferry, MD, of the CRC
Institute for Cancer Studies, University of Birmingham, UK, explained
at an ASCO press conference.
Dr. Ferry and Jose M. Baselga, MD, Vall dHebron General
Hospital, Barcelona, Spain, presented final results of two phase I
studies of Iressa among patients with five tumor typesovarian
cancer, colorectal cancer, prostate cancer, head and neck cancer, and
nonsmall-cell lung cancer (NSCLC).
Dr. Baselga discussed results from two dose-escalation studies among
159 patients taking Iressa orally twice on day 0 and once daily for
28+ consecutive daysuntil disease progression or significant
toxicity is noted.
Overall tolerability was good, Dr. Baselga said. The most common
adverse events were skin rash (58%), minor GI toxicity (47%), and
easily controlled grade 1 or 2 diarrhea (44%). The maximum tolerated
dose was 1,000 mg.
Partial responses were reported in one patient with NSCLC and in one
with prostate cancer. In pretreated patients, stable disease
for a duration of at least 3 months has been observed in all five
tumor types studied, Dr. Baselga said. The rate of combined
response plus stable disease (3 months or more) was 25% in NSCLC, 28%
in ovarian, 23% in colorectal, 29% in prostate, and 54% in head and
neck tumors. The overall rate was 30%.
Intermittent Dosing Trial
Dr. Ferry reported a trial assessing intermittent dosing of Iressa
(14 days on and 14 off) at a maximum dose of 700 mg once daily. The
trial was designed to evaluate the tolerability and activity of
Iressa in escalating doses in patients with solid malignant tumors
known to express or overexpress EGFr. Patients showing no progression
at 28 days continued for further courses.
The trial included 64 patients (median age, 53; median WHO
performance status, 1). Patients had all received at least one prior
treatment. Tumor types included 16 NSCLC, 8 ovarian, 8 breast, 6
colorectal, 4 esophageal, 2 prostate, and 2 head and neck.
Investigators were pleasantly surprised to find
toxicities limited to easily controlled diarrhea and acnelike rash,
Dr. Ferry reported. At the 700-mg dose, plasma levels well above
target were achieved.
Confirmed Partial Responses
There were confirmed partial responses in two heavily pretreated
NSCLC patients (at 400 mg and 525 mg), noted Dr. Ferry. Not
only was there an objective radiologic response but, importantly,
there was palliation, he said. Dr. Ferry also said that
breathing was improved, and that some patients had less need for pain
Antitumor response was most evident among the 16 lung
cancer patients, Dr. Ferry stated, pointing out that beyond the
two partial responses, there were two patients with significant
regression and two with stable disease.
He added that evidence of tumor regrowth in the interval off
study may suggest that intermittent dosing is not the optimal schedule.
Dr. Ferry concluded, Iressa is a medication that is easy for
patients to take. It is well tolerated with minimal side effects. To
our surprise, it is active as a single agent, at least in
nonsmall-cell lung cancer. Patients with other kinds of cancers
had stable disease for up to 4 months.
A series of clinical trials is being planned to explore Iressas
role as monotherapy and in combination with chemotherapy, he added.