FRIDAY, Jan. 19 (HealthDay News) -- A trial testing whether the chemotherapy drug mitoxantrone would benefit men with prostate cancer has been stopped because three of the 488 patients who received the drug developed leukemia.

According to the Southwest Oncology Group, which was running this phase III trial, 983 patients were randomly assigned to receive hormone deprivation therapy alone or hormone deprivation therapy plus six doses of mitoxantrone.

"We were surprised by the incidence of leukemia," said principal investigator Dr. L. Michael Glode, a professor of medical oncology at the University of Colorado in Denver. "This general category of drugs has been associated with leukemia."

One expert thinks the decision to end the trial was correct.

"They are doing the right thing," said Dr. Anthony D'Amico, chief of radiation oncology at Brigham and Women's Hospital, in Boston. "The initial studies of mitoxantrone were done in men with end-stage prostate cancer -- but their life expectancy was about a year and a half. The life expectancy of the men in this study is 10 to 15 years or more. Only in a study like this can you see the long-term side effects of chemotherapeutic agents like mitoxantrone."

However, another expert doesn't see anything unusual about the incidence of leukemia among men receiving mitoxantrone.

"This is the first trial that tested adjuvant chemotherapy in men with high-risk prostate cancer," said Dr. Mario Eisenberger, a professor of oncology at Johns Hopkins University. "I wouldn't be so alarmed with the very low number of leukemias in this setting, especially if you put that against the possible gain that you can get from this approach."

Mitoxantrone has been approved for use in prostate cancer as well as in breast cancer, and it is commonly used to treat multiple sclerosis. In this trial, mitoxantrone was being used to treat "poor risk" prostate cancer patients. These are men whose cancer has spread to the tissues next to the prostate, or whose cancer has a high probability of returning after surgery or radiation therapy.

The trial was stopped on Jan. 12 after the Southwest Oncology Group's Data Safety Monitoring Committee reviewed side effects and survival. The committee found that no patients in the hormone deprivation-only group developed leukemia, which suggested there was an increased risk of leukemia from mitoxantrone.

Another expert wasn't surprised that there appears to be an association between mitoxantrone and leukemia in these men.

"It is well known that mitoxantrone is associated with a small, but real, increased risk of leukemia," said Dr. Celestia Higano, an assistant professor of medicine and urology at the University of Washington. "The incidence of leukemia in this trial is on target with what has been seen in breast cancer. This is not unexpected."

Glode also noted there have been similar incidences of leukemia with the drug among patients with breast cancer and with multiple sclerosis. "The drug is approved for treating leukemia and for prostate cancer," he said. "We don't know if mitoxantrone is the culprit here; it could just be a cluster of cases because the percentage is so small."

Despite closing the trial early, it is going to take years of monitoring the patients to really determine whether or not mitoxantrone actually has a benefit for men with prostate cancer, Higano said.

"We are going to have to wait a number of years to see if there isn't, at the end of the day, some potential survival benefit, even though it was at the cost of some patients developing leukemia," Higano said.

It will take up to 10 years to see if the drug had a survival benefit, Glode noted. "At this point, patients in both arms of the trial are doing better," he said. "That may be due to the hormone treatment. The trial will take another eight to 10 years to determine if there was a benefit from the chemotherapy drug."

Eisenberger thinks these trials, despite some drawbacks, are essential to find ways to save lives.

"We would like to see the continued support for the kinds of trials we are doing," Eisenberger said. "We are really trying to see if we can save more lives. People will die of the disease; people will die of the consequences of treatment, but the net benefit in the end is that you save thousands of lives at the cost of a very small proportion, which really saddens me, but life is not perfect."

Both Eisenberger and Higano are concerned that the fallout from this trial will affect other trials. "Some degree of alarm over these findings is going to make people hesitant to continue with research in this area," Higano said. In addition, Higano is concerned that doctors will stop referring patients to trials because of the halting of this trial.

More information

The U.S. National Library of Medicine can tell you more about mitoxantrone.