Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Lung Cancer Home Page 2 NCI's gateway for information about lung cancer. Highlights from ASCO 2005 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2005 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Small cell lung cancer, irinotecan, etoposide, cisplatin. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

A combination of the drugs irinotecan and cisplatin was no better than the standard treatment at helping patients with extensive small-cell lung cancer (SCLC) live longer. These findings from a U.S. study differ from those of an earlier Japanese study.

Source

American Society of Clinical Oncology (ASCO) annual meeting. Orlando, May 14, 2005.

Background

About two-thirds of patients with small cell lung cancer have difficult-to-cure extensive disease when their cancer is first found. The standard treatment for extensive-stage small cell lung cancer is a combination of the drugs etoposide, which is a topoisomerase inhibitor thought to interfere with the growth and replication of cancer cells, and cisplatin. Researchers are testing other drugs and drug combinations in an effort to improve the current median survival time (about 10 months).

Irinotecan is another anticancer drug in the category of topoisomerase inhibitors. In 2002, results were published from a phase III trial in Japan that was stopped early when a preliminary analysis showed that patients with extensive-stage SCLC who were being treated with irinotecan plus cisplatin were living longer than those treated with the standard etoposide plus cisplatin regimen (see the journal abstract). The current trial was launched to see if these preliminary findings could be confirmed.

The Study

In this phase III trial, 331 patients with extensive-stage SCLC were randomly assigned to receive either irinotecan plus cisplatin (221 patients) or etoposide plus cisplatin (110 patients). The trial was “open label” – that is, both patients and their doctors knew which drug combination the patients were receiving. All patients were enrolled between December 2000 and June 2003, and none had yet received chemotherapy for their disease. The research team was led by N. H. Hanna, M.D., of Indiana University in Indianapolis.

Results

In contrast to the earlier Japanese trial, there was no statistically significant difference in survival offered by the irinotecan/cisplatin combination. The one-year survival rate for the irinotecan group was 35 percent compared to 36.1 percent for the etoposide group.

There was also no statistically significant difference between the groups in terms of the cancer’s rate of response to treatment (52 percent vs. 51 percent); median time to disease progression (4.1 percent vs. 4.6 percent); or median survival (9.3 months vs. 10.2 months).

Similar to the Japanese study, patients in the irinotecan group were more likely to experience serious nausea, vomiting, diarrhea, and dehydration while the etoposide group was more likely to suffer potentially dangerous suppression of their bone marrow function.

Limitations

Hanna acknowledged that their results may differ from the other study because of different characteristics in the Japanese and American patient populations. For example, there may be underlying genetic differences between the two populations that would cause the same drug to be metabolized in different ways. But the genomic data that might have addressed this question were not gathered.

It is also possible the difference in survival rates between the U.S. and Japanese studies can be explained by the slightly different way the irinotecan regimen was given in the U.S. study, though the authors say this isn’t likely. “We modified the regimen [from the Japanese trial] to improve its tolerability, achieve greater dose intensity, and maintain or even improve its efficacy,” he explained.

Comments

Despite the earlier promising results, there appears to be no meaningful difference in outcomes between the irinotecan and the epotoposide regimens for patients with extensive-stage SCLC. Patients lived about as long and found their disease recurred about as often, irrespective of which drugs they were given. It is significant, said Hanna, that the side effects found in both studies were consistent. “Despite our best efforts to modify the impact of irinotecan, the rates of nausea and vomiting were similar to that on the Japanese study.”

Glossary Terms

A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent. Also called Platinol.

A drug used to treat testicular and small cell lung cancers. It is also being studied in the treatment of several other types of cancer. Etoposide blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of podophyllotoxin derivative and a type of topoisomerase inhibitor. Also called Toposar and Vepesid.

The active ingredient in a drug used alone or in combination with other drugs to treat colon cancer or rectal cancer that has spread to other parts of the body or has come back after treatment with fluorouracil. It is also being studied in the treatment of other types of cancer. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of topoisomerase inhibitor and a type of camptothecin analog.

A statistics term. The middle value in a set of measurements.

The time from either diagnosis or treatment at which half of the patients with a given disease are found to be, or expected to be, still alive. In a clinical trial, median survival time is one way to measure how effective a treatment is. Also called median overall survival and median survival.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

A substance that blocks topoisomerases (enzymes that break and rejoin DNA strands and are needed for cells to divide and grow). Blocking these enzymes may kill cancer cells. Certain topoisomerase inhibitors are being studied in the treatment of cancer.