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Key Words

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

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.”

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