Originally created 11/04/04

Study: Patient deaths decline in early studies of new cancer drugs



CHICAGO - Early studies of experimental cancer drugs appear to be getting safer, according to a study that found a sharp drop in patient deaths from 1991 to 2002.

At the same time, there was also a decline in the percentage of tumors that shrank in response to the drugs being tested. But the researchers and other cancer experts said that does not mean the drugs were increasingly ineffective.

Some of the newest cancer drugs employ a more targeted approach than older medicines, attacking tumor cells while causing less damage to healthy tissue. These drugs often work by stopping but not necessarily reversing tumor growth, said Dr. Thomas Roberts Jr. of Massachusetts General Hospital, the study's lead author.

The development of such drugs plus better attention to patient safety may explain the declining death rate, Roberts said.

There were 35 drug-related deaths in the 213 studies examined, but such deaths were much more frequent in the earlier experiments than in the more recent ones. There were 24 drug-linked deaths in studies from 1991 to 1994, 10 from 1995 to 1998 and just one from 1999 to 2002.

Deaths from other causes, including cancer, also decreased - from 39 to 17 in the more recent studies.

Dr. Mace Rothenberg, a Vanderbilt University cancer research specialist who was not involved in the study, called the findings "clearly good news."

"It indicates that patients who agree to go on to these fairly risky studies are not placing themselves at an unacceptably high risk for severe toxicity or death," he said.

The studies involved 6,474 patients, and the overall death rate fell from 3 percent to 1 percent.

The researchers said there has been increased oversight of human experiments during the past decade. For example, they said, many institutions have developed educational programs for researchers and hired additional staff to oversee research.

Roberts said it was encouraging to find not only fewer drug-linked deaths, but also a decline in cancer-related deaths.

"They are significant because this is something that really matters to patients I think when they are considering whether to proceed with standard treatments or experimental treatments," Roberts said.

His report appears in Wednesday's Journal of the American Medical Association.

The studies involved were Phase I clinical trials, the first time experimental drugs are tested in humans. These are small studies designed mainly to test the safety of an experimental treatment and to determine the maximum tolerable dose.

Patients who participate in Phase I cancer studies generally have advanced disease that has not responded to conventional treatments. While many hope participating will improve their health, that is not the primary goal in such studies.

The patients involved had various types of cancer, including colon, lung, kidney, breast and prostate tumors.

Roberts said the results are particularly encouraging because of heightened concern over the safety of human research following the deaths of two patient volunteers in non-cancer studies at the University of Pennsylvania and Johns Hopkins University in recent years.

But University of Pennsylvania ethicist Arthur Caplan said while the study is enlightening, it included only studies of ailing cancer patients and doesn't address "the core battleground" over the ethics of using healthy human volunteers in early research.