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Targeted Therapies: New Spin on an Old Concept?

Targeted Therapies: New Spin on an Old Concept?

ORLANDO—Evolving targeted therapies for metastatic colorectal cancer
hold promise for greater therapeutic efficacy and improved quality of life
for patients, according to Edward H. Lin, MD, assistant professor of
medicine, Division of Gastrointestinal Medical Oncology, M.D. Anderson
Cancer Center. Speaking at an industry-sponsored symposium held in
conjunction with the ASCO meeting, Dr. Lin discussed the general concepts of
targeted therapy and reviewed several treatments under investigation.

"Targeted therapy is an ‘old concept’ in the context of new
knowledge about carcinogenicity," Dr. Lin said. "Even 5-FU
[fluorouracil], capecitabine [Xeloda], and irinotecan [CPT-11, Camptosar]
are targeted therapies in a way. Now, Gleevec [imatinib mesylate] acting
with c-KIT and Iressa [investigational] acting through the EGFR mechanisms
are just another way of delivering molecularly targeted therapies."

Two misconceptions about targeted therapies are that they are merely
cytostatic and that they are less toxic, Dr. Lin noted. "These agents
are not exactly cytostatic. They can clearly induce tumor apoptosis as well
as tumor deaths," he said. "We clearly need to validate their
molecular targets, know their mechanism of action, and really try to
modulate and reverse cancer hallmarks, such as angiogenesis, with these
targeted agents."

Targeted therapies do have their own characteristic toxicities, Dr. Lin
added, such as hand-foot syndrome with capecitabine and skin rash with EGFR
inhibitors. But their important advantages are improved delivery, especially
oral delivery, and improvements in the therapeutic index.

"Certainly, the pharmaceutical companies recognize that the future
direction is oral-based chemotherapy," he said. "And many of the
new chemotherapies—Iressa, COX-2 inhibitors, and Gleevec—are oral

Oral delivery is convenient and allows flexibility for patients and their
caregivers, especially for those who work or want to travel, he said. It
per-mits flexible dose adjustment and allows treatment to be easily tailored
to each patient’s toxicities. Oral delivery is economical and is an
efficient use of resources.

Dr. Lin pointed to HAART [highly active antiretroviral therapy] being
used to treat HIV disease as a model of what can be achieved with these
types of therapies. "We really should be drawn to the fact that the
HAART therapy in HIV disease is an enormous success story," Dr. Lin
said. "Many of these patients have returned to a normal quality of
life, with essentially every-3-month follow-up."


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