Iressa Shows Promising Antitumor Activity and is Well Tolerated With Minimal Side Effects

BIRMINGHAM, United Kingdom—Early 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 d’Hebron General Hospital, Barcelona, Spain, presented final results of two phase I studies of Iressa among patients with five tumor types—ovarian cancer, colorectal cancer, prostate cancer, head and neck cancer, and non–small-cell lung cancer (NSCLC).

Dose-Escalation Studies

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 days—until 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 control.

 “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 non–small-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 Iressa’s role as monotherapy and in combination with chemotherapy, he added.