Experimental chemotherapy regimen shows promise in treating advanced lung cancer

August 12, 2008

PHILADELPHIA - A combination of chemotherapy agents that have been tested in other tumor types appears to be a promising alternative to standard treatment for advanced non-small cell lung cancer, according to a report in the August 15 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research.

In a phase II multicenter study of 56 patients with an advanced form of this common lung cancer, endpoints including response rate, progression-free survival, and overall survival from use of S-1 and irinotecan were similar to, or better than, those reported from standard treatment with platinum-based chemotherapy regimens.

Because the study had only a single arm - meaning all patients received the experimental therapy - the researchers cannot say if this regimen offers more benefit than standard treatment. But they did report that side effects resulting from the experimental therapy appeared to be much less severe than those typically seen with standard treatment.

"There continues to be reluctance on the part of both patients and treating physicians to accept the toxicity of platinum-based therapy, given the associated small gain in survival, so active therapies with improved toxicity profiles are clearly needed," said the study's lead investigator, Isamu Okamoto, M.D., Ph.D., associate professor in the Department of Medical Oncology at the Kinki University School of Medicine in Osaka, Japan.

Okamoto says that a direct comparison between this experimental regimen and platinum-based "doublet" chemotherapy should be conducted to confirm what appears to be a survival benefit among patients who used S-1 and irinotecan.

S-1 (also known as TS-1) is approved for use in Japan and Korea, where it has shown substantial benefit in treating gastric cancer, but is still in clinical trials in other countries, including the U.S. and Europe.

The multifaceted agent, which is available in capsule form, has three different mechanisms of action. One part breaks down into active fluorouracil (5-FU) once it is in the body. 5-FU is a chemotherapy drug often used to treat colorectal and other cancers.

Another part of S-1 keeps 5-FU production at a steady level and a third part is designed to counteract 5-FU's toxic effects, such as nausea and vomiting.

Irinotecan, an intravenous drug originally developed and tested in Japan and approved for use in the U.S. in 1994, is most often used to treat colon cancer. It is currently being used in Japan to treat lung cancer, but is not commonly used in this way in other countries, says Okamoto.

The combination of these two agents appears to offer a synergistic effect, he says. When S-1 was tested as first-line chemotherapy for advanced lung cancer, the response rate was 22 percent with a median survival time of 10.2 months. In this study, patients who had not received any treatment for their advanced lung cancer were enrolled at 14 centers in Japan and received a median of five cycles of treatment. The response rate for the combination therapy was 28 percent, median progression-free survival was 4.9 months and median overall survival was 15 months.

Okamoto says these findings compare favorably with previous studies of platinum-based doublets, which demonstrated response rates of 17 to 33 percent, a median time to progression or progression-free survival of three to five months, and a median overall survival time of seven to 14 months. "This is a promising alternative, but needs further testing in randomized trials," he said.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

American Association for Cancer Research

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