Developments to Watch
Dispatches from the War on Cancer
Cancer treatment is about to undergo a sea change, bringing new drugs that precisely target the causes of tumor growth. In five or six years, patients may no longer be told they have something called lung or breast cancer, predicts Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center, one of the world's leading researchers. Instead, a cancer will be defined by the cellular mechanism that causes it, and therapy will be tailored to that mechanism--much the way an infection is treated. Drugs will home in on the agents of disease without harming healthy tissue. "What we are seeing today could be the beginning of the end of chemotherapy," Norton told BusinessWeek at the annual meeting of the American Society of Clinical Oncology in San Francisco, May 12-15. Although many of the clinical trial results discussed at the meeting are still in very early phases, the excitement among the 25,000 attendees was palpable. Senior writer Arnst reports:
Chemo without the Side Effects
Some experimental cancer drugs target an enzyme called the epidermal growth factor. It triggers cell growth and division--and it is found in more than 50% of all cancers. In healthy people, EGF is in scarce supply. But in the early 1980s, researchers discovered that it is expressed at very high levels in cancer patients with advanced disease, most likely churned out by cancer-related genes. The goal with EGF drugs is to block the "receptor" for the enzyme on the surface of cancer cells. (Receptors are docking areas on cells that bind with proteins in the bloodstream.)
The most advanced EGF-blocking drug is ImClone Systems' IMC-C225, which is under accelerated review at the Food & Drug Administration. Dr. Leonard Saltz of Sloan-Kettering reported significant tumor shrinkage in 27 of 120 patients with widespread colorectal cancer who didn't respond to other treatments. That 22.5% response rate is considered very high in a trial with such sick patients. Plus, the disease was completely stabilized in another nine patients. The main side effect, as with most other EGF blocking agents, was an acne-like skin rash--a minor discomfort compared with the side effects of existing chemotherapies. ImClone, based in New York, is also testing IMC-C225 in pancreatic, head, neck, and lung cancers, and says it expects to file for FDA approval in June.
Taking Aim at Cancer
Experimental drugs that attack the tumor, not the patient
DRUG TARGET STATUS
IMC-C225 Blocks the epidermal Phase II/III trials for
ImClone growth factor receptor, colorectal, pancreatic,
Systems found in more than head and neck, and
half of all cancer non-small-cell lung
types cancers. The FDA has
granted fast-track
approval status
GVAX A vaccine that trains Phase I/II trials for non-
Cell Genesys the patient's immune small-cell lung cancer,
system to attack prostate, pancreatic, and
tumor cells myeloma cancers
ABT-627 Blocks the endothelin- Phase II/III trials for
Abbott A receptor, which aids advanced prostate cancer
Laboratories the cancer
SU5416 Blocks growth-factor Phase III trials for colo-
Pharmacia signals sent by tumors rectal cancer, Phase II
to stimulate blood trials for a number of
vessel growth, which solid tumors, including
allows them to spread breast cancer
Enlisting Antibodies in the Battle
Tumors can be deadly, but because they are homegrown, they fool the body's defense mechanisms. Several labs are trying to goose the immune system into attacking cancer cells through the use of vaccines. One that has attracted attention is the GVAX vaccine from Cell Genesys of Foster City, Calif. To immunize a patient, doctors participating in Cell Genesys' trial remove whole tumor cells and genetically engineer them to secrete a hormone called GM-CSF, which plays a key role in stimulating the body's immune response. Doctors then reinject the cells into the patient.
In an early-phase clinical trial of 80 patients with lung cancer, 11 have completed the GVAX therapy. Of those, three with advanced, untreatable cancer went into remission. In another three with early-stage cancer, the tumors stopped growing. "GVAX has produced one of the most dramatic responses I have seen with an experimental agent," says lead investigator Dr. John Nemunaitis of US Oncology in Dallas.
Therion Biologics of Cambridge, Mass., takes a different approach. It employs a neutralized pox virus, known to stimulate immune-system responses, combined with a protein found on the surface of tumor cells. In a trial of nine patients with a range of late-stage cancers--patients whose usual life-expectancy is less than one year--five were still alive after two years.
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Copyright 2001 , by The McGraw-Hill Companies Inc. All rights reserved.
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