ORLANDOEvolving 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(Drug information on capecitabine) [Xeloda], and irinotecan(Drug information on 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 chemotherapiesIressa, COX-2 inhibitors, and Gleevecare oral based."
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."