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 2006 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Non-small cell lung cancer; brain metastases; motexafin gadolinium; whole-brain radiation therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

The addition of the drug motexafin gadolinium to whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer significantly delayed the progression of brain damage. The amount of time between the diagnosis of metastases and the start of therapy correlated with the benefit of the treatment—delayed therapy was less effective.

Source

American Society of Clinical Oncology (ASCO) annual meeting, Atlanta, June 3, 2006 (see the meeting abstract ⁵).

Background

Non-small cell lung cancer (NSCLC) often spreads (metastasizes) to the brain. Brain metastases are associated with a poor prognosis and can greatly decrease patients’ quality of life. Whole-brain radiation therapy is currently the standard treatment for brain metastases, but offers only a short reprieve from disease progression.

The drug motexafin gadolinium (MGd) can kill cancer cells and, in addition, possibly make remaining cancer cells more susceptible to radiation therapy. A previous trial showed that the addition of MGd to whole-brain radiation therapy significantly delayed further brain damage in patients with brain metastases from NSCLC. However, this analysis was done after the trial was finished (retrospectively). A prospective randomized trial specifically designed to look at this question was needed to confirm the results.

The Study

In the international phase III SMART trial (Study of neurological progression with Motexafin gadolinium And Radiation Therapy), investigators from eight countries enrolled 544 patients with brain metastases from NSCLC. Three hundred and forty-eight patients were from North America and 206 from Europe and Australia.

The patients were randomly assigned to one of two groups: 279 patients received whole-brain radiation therapy plus MGd, and 275 received whole-brain radiation therapy alone. After therapy, patients returned for follow-up every month for eight months, and then every two months thereafter.

The investigators measured the time it took for brain damage to progress (called neurological progression) as well as time to death. To minimize bias, a central committee judged decline in neurological function for all patients.

The trial was sponsored by Pharmacyclics, the pharmaceutical company that developed MGd. The study’s lead author is Minesh Mehta, M.D., Professor and Chair of Human Oncology at the University of Wisconsin, Madison.

Results

The combination of MGd and whole-brain radiation therapy was well tolerated - side effects were mostly mild, and more than 92 percent of MGd doses were given as planned.

When the investigators measured the time from randomization to neurological progression, they found a benefit of about five months (15.4 months with whole-brain radiation therapy plus MGd versus 10 months for whole-brain radiation therapy alone). This difference was not statistically significant. However, when they measured the time from diagnosis (rather than randomization) to neurological progression, they did find a statistically significant benefit for the MGd group.

Upon further analysis of the data, the investigators realized that some doctors had delayed enrolling patients in the trial up to several months after diagnosis. In some cases, patients had received chemotherapy before enrolling in the trial. To clarify the benefit of early therapy with whole-brain radiation therapy and MGd, the investigators looked at patients from North America, who had a short average time from diagnosis to trial enrollment, in a separate analysis.

In North American patients, time to neurological progression was significantly prolonged with the addition of MGd to whole-brain radiation therapy, from 8.8 months with whole-brain radiation therapy alone to 24.2 months with whole-brain radiation therapy plus MGd.

Limitations

One limitation of the study was that investigators could not have predicted differences in the usual patterns of care around the world, such as doctors choosing to delay patients’ entry into the trial in order to give them chemotherapy first, said lung cancer specialist Eva Szabo, M.D., of the National Cancer Institute’s Division of Cancer Prevention. Looking at the overall results – not just those from the North American patients, who did not receive chemotherapy first - investigators cannot be sure if the delay affected patients’ experience with the trial treatment, or if those patients were also different in some other way.

Comments

Overall, “The time interval from brain metastases diagnosis to randomization predicts the treatment effect,” said Mehta, the study’s lead author. Therefore, MGd plus whole-brain radiation therapy is most effective when given soon after brain metastases are discovered.

“Brain metastases from non-small cell lung cancer present a difficult problem,” said Szabo. “This study represents an interesting approach that will hopefully translate into better care for patients.”

Glossary Terms

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

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.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

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.