A subcommittee of the Oncologic Drugs
Advisory Committee (ODAC) recently spent a day discussing the similarities and
differences between pediatric and adult hematologic malignancies. It was the
second session in a series intended to advise the Food and Drug Administration
(FDA) on how to apply its 1998 Pediatric Rule regarding the testing of cancer
drugs in children. The rule states that "there is a federal mandate to
perform pediatric studies if the indication under review for a marketing license
exists in children."

Subcommittee members and a panel of cancer specialists
addressed application of the rule in three areas: myeloid leukemia and
myelodysplastic syndrome, lymphoblastic leukemia, and lymphomas.

Ethical Dilemma

In his introductory comments, David G. Poplack, MD, professor
of pediatric oncology at Baylor College of Medicine, touched on a fundamental
issue of testing new drugs in children that are intended for adult use. He cited
acute lymphocytic leukemia (ALL), for which conventional cytotoxic therapy has a
good survival record in youngsters. If a new drug shows promise in adults, it
can be a challenge for pediatric clinical researchers to decide whether to test
it in children, he said.

"On the one hand, you can say, how is it ethical to
change the regimen?" said Dr. Poplack. "However, you can make a strong
argument to the contrary. We know that many curative therapies are associated
with toxicity. If you have something that is more specific—that may have fewer
toxicities—you may be ethically bound to study that drug vs the combination
therapies that may cure ALL but have high toxicities."

Although the FDA relies on ODAC for advice and guidance in
approving the marketing of cancer drugs and biologic agents, as well as other
issues relating to its regulatory responsibilities, the agency is under no
obligation to accept any ODAC recommendation.

Questions Posed by the FDA