Second round of gefitinib worth trying in NSCLC

NEW YORK (Reuters Health) - When disease progression develops in patients with non-small cell lung cancer (NSCLC) that initially responded to gefitinib, retreatment with the same drug will be helpful in a "significant proportion" of cases, Korean researchers announced at a conference in California this week.

Re-initiation of gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), will "help maintain quality of life for several months," said Dr. In-Jae Oh of Chonnam National University Hwasun Hospital in Gwangju.

However, before retreatment, "progressive disease should be observed with at least one cytotoxic treatment following initial gefitinib failure," according to the poster presentation made by Dr. Oh and associates at the Conference on Molecular Origins in Lung Cancer in Coronado.

The conference is jointly sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

For their single-arm, open-label, prospective phase II trial, Dr. Oh and colleagues recruited 15 patients with NSCLC who had initially responded to gefitinib with partial remission (n=6) or stable disease (n=9). The median length of initial gefitinib treatment was 263.5 days (range 106 to 435 days).

When their disease progressed, each patient had received at least one cycle of chemotherapy.

Then, in Dr. Oh's study, the patients received 250 mg gefitinib orally once a day for a median of 85.5 days (range 14 to 206 days).

Two of the six patients who had partial responses to initial gefitinib treatment had partial responses to retreatment, and three responded with stable disease, for a disease control rate of 83.3%.

Five of the nine patients who responded to initial treatment with stable disease had stable disease again after retreatment, and another two had partial responses to retreatment, for a disease control rate of 77.7%.

The overall disease control rate was 80.0%.

Tumor heterogeneity probably explains the response to retreatment, Dr. Oh said. The cells that have learned to survive independently of EGFR won't respond to EGFR inhibition, "but we can continue to target the other cells" that still depend on EGFR for survival.

Despite the small number of patients in the study, the results suggest that factors such as activation of a mutation of the EGFR gene; initial good response to EGFR-TKI for more than 3 months; being a female who never smoked; and the histology of the adenocarcinoma can predict another response to EGFR-TKI, Dr. Oh told Reuters Health.

Ten of the 12 patients who had favorable responses were female never-smokers, he said.

Dr. Oh sees no downside to gefitinib retreatment versus trying another type of therapy. Re-initiation of EGFR-TKI can relieve symptoms and trigger another remission, and "in patients who don't respond to a second round of treatment after a short-term trial, we can start another treatment."

"I don't think a 1- or 2-month trial" of a second round of gefitinib "is harmful to patients with repeatedly relapsed lung cancer," he said.

Gefitinib is sold in the US by AstraZeneca under the trade name Iressa.

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