Re-treatment with gefitinib curbs disease progression

CORONADO, Calif.-A second round of gefitinib (Iressa) slowed disease advancement in non-small-cell lung cancer patients who failed to respond to first-line treatment, according to a study presented at the 2010 Joint Conference on Molecular Origins in Lung Cancer.

The lack of an established therapeutic option for NSCLC patients who have progressive disease after anti-EGFR-TKI failure poses a major challenge to physicians, said lead investigator In-Jae Oh, MD, PhD, an assistant professor at Chonnam National University and Hwasun Hospital in Gwangju, Korea.

Dr. Oh and colleagues hypothesized that reintroducing gefitinib therapy might bring about significant clinical and radiological improvements, or disease stabilization, in a certain percentage of NSCLC patients with progressive disease.

Their study population consisted of seven patients who had partial remission and 11 patients who had stable disease as their initial response to gefitinib. Before re-treatment with gefitinib (250 mg/d), the patients had to demonstrate progressive disease with at least one cytotoxic treatment following initial gefitinib failure.

The investigators evaluated 15 patients after re-treatment with gefitinib. Among the six patients who showed partial remission with initial gefitinib treatment, two showed an additional partial remission when re-treated with gefitinib, and three patients continued to show stable disease for a disease control rate of 83.3%.

Among the nine patients who showed stable disease with initial gefitinib treatment, two patients showed partial remission and three patients showed stable disease with re-treatment, for a disease control rate of 55.6% (abstract B24).

"After failure with gefitinib and subsequent chemotherapy, we can try gefitinib again especially for the patients who had previously responded to gefitinib," Dr. Oh said. "This strategy will keep some patients from the toxicities of chemotherapy and help maintain the quality of life for several months."

The conference was sponsored by the AACR and the International Association for the Study of Lung Cancer.

Vantage Point

Gefitinib serves as option after standard therapy

The main reason for disease progression after an extended response to gefitinib is the development of secondary mutations, said Dr. Bunn, professor of medicine and James Dudley Chair in Cancer Research at the University of Colorado in Denver.

"When that resistance mutation occurs, it's generally in a minority of the tumor cells," he said. "The majority still have the original activating mutation. So even in the absence of progression, there are many cells that will remain sensitive."

This study has clinical implications, Dr. Bunn said. He pointed out that, in general, the same chemotherapy is not repeated if the patient has disease progression. "This study is suggesting that even if you have progression, some sensitive cells remain, and it may be worth going back on [gefitinib] after your next treatment is given."

Standard chemotherapy is usually not given simultaneously with gefitinib or erlotinib (Tarceva) because of negative interactions, Dr. Bunn said. "But when you finish with the standard chemotherapy, you can put patients back on erlotinib or gefitinib. That is currently my standard of practice."