New Drug Shows Promise Against Certain Lung
WEDNESDAY, Oct. 27 (HealthDay News) -- An experimental cancer
drug is proving effective in treating the lung cancers of some
patients whose tumors carry a certain genetic mutation, new studies
Because the mutation can be present in other forms of cancer --
including a rare form of sarcoma (cancer of the soft tissue),
childhood neuroblastoma (brain tumor), as well as some lymphomas,
breast and colon cancers -- researchers say they are hopeful the
drug, crizotinib, will prove effective in treating those cancers as
In one study, researchers identified 82 patients from among
1,500 patients with non-small-cell lung cancer, the most common
type of lung malignancy, whose tumors had a mutation in the
anaplastic lymphoma kinase (ALK) gene.
Crizotinib targets the ALK "driver kinase," or protein, blocking
its activity and preventing the tumor from growing, explained study
co-author Dr. Geoffrey Shapiro, director of the Early Drug
Development Center and associate professor of medicine at
Dana-Farber Cancer Institute and Harvard Medical School,
"The cancer cell is actually addicted to the activity of the protein for its growth and survival," Shapiro said. "It's totally dependent on it. The idea is that blocking that protein can kill the cancer cell."
In 46 patients taking crizotinib, the tumor shrunk by more than
30 percent during an average of six months of taking the drug. In
27 patients, crizotinib halted growth of the tumor, while in one
patient the tumor disappeared.
The drug also had few side effects, Shapiro said. The most
common was mild gastrointestinal symptoms.
"These are very positive results in lung cancer patients who had received other treatments that didn't work or worked only briefly," Shapiro said. "The bottom line is that there was a 72 percent chance the tumor would shrink or remain stable for at least six months."
The study is published in the Oct. 28 issue of the
New England Journal of Medicine.
In recent years, researchers have started to think of lung
cancer less as a single disease and more as a group of diseases
that rely on specific genetic mutations called "driver kinases," or
proteins that enable the tumor cells to proliferate.
That has led some researchers to focus on developing drugs that
target those specific abnormalities. "Being able to inhibit those
kinases and disrupt their signaling is evolving into a very
successful approach," Shapiro said.
The good news is that drugs such as crizotinib seem to work well
in patients with the mutation, noted Dr. Roman Perez-Soler,
chairman of the department of oncology at Montefiore Medical Center
and professor of medicine and molecular pharmacology at the Albert
Einstein College of Medicine in New York City. But the bad news is
that it means that patients who don't have the specific mutation
won't be helped.
Only an estimated 2 percent to 7 percent of non-small-cell lung
cancers have the ALK mutation, according to the study.
"This is great news for people with this type of tumor," Perez-Soler said. "Researchers have identified a group of patients, unfortunately a small group, who because of a very specific genetic abnormality are extremely sensitive to these targeted treatments and as a result of that can benefit from this drug without toxicity. It's very encouraging."
In a second study in the same journal, crizotinib was effective
in a 44-year-old man with inflammatory myofibroblastic tumor, a
rare form of sarcoma, which is also driven by the ALK abnormality,
said Shapiro, who was senior author of that paper.
Still, there are caveats. Over time, tumors can adapt to such
targeted therapy, eventually rendering it ineffective, experts
said. In fact, a third study in the same journal identified ways in
which lung cancers had already started to mutate and overcome
Moreover, while drugs targeting a specific tumor genotype are
promising, there could be so many different genotypes that it would
be impractical to come up with drugs targeting all of them,
Perez-Soler said. Still other tumors might be fueled by multiple
"Many cancers may be much more complicated," he said. "And every tumor is different. Each one has a number of sophisticated ways to overcome interventions to block growth, and some may be better prepared than others to do that. That is why you see heterogeneity in the response to the drug. There is no such thing as identical twins when we talk about tumors."
Researchers are currently enrolling patients for a larger, Phase
III clinical trial of crizotinib, Shapiro said. The study was
funded by Pfizer, which is developing crizotinib for clinical
application, and by grants from the U.S. National Cancer Institute,
Lung cancer remains one of the most deadly cancers and new
treatments are desperately needed, the researchers said. "Advanced
lung cancer still remains a very lethal disease," Shapiro said.
"It's the biggest cancer killer of both men and women in the U.S.
and worldwide, and the unmet clinical need is extreme."
Find out more about non-small-cell lung cancer at the
U.S. National Cancer Institute.
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