Lung cancer patients with pockets of resistance prolong disease control by 'weeding the garden'

December 1, 2012, University of Colorado Denver

The central skill of cancer is its ability to mutate – that's how it became cancerous in the first place. Once it's started down that path, it's not so difficult for a cancer cell to mutate again and again. This means that different tumors within a single patient or even different areas within the same cancerous deposit may develop different genetic characteristics. This heterogeneity helps cancer escape control by new, targeted cancer therapy drugs.

Two of these targeted drugs are crizotinib and – they do wonders for the patients whose cancers depend on the basic mutations that these drugs exploit. That is, until pockets of the cancer mutate again, pivoting their dependence away from the original, targeted mutation. Due to continuing mutation, the unfortunate reality is that while crizotinib and erlotinib extend patients' lives, the drugs eventually, inevitably, inexorably stop working.

A University of Colorado Cancer Center study published in the December issue of the International Association for the Study of 's (IASLC) shows that when pockets of resistant cancer develop, it's often possible to zap these resistant pockets with focused, targeted radiation while continuing crizotinib or erlotinib to maintain control of the majority of the disease that continues to depend on the primary mutation.

"We liken this to weeding the garden," says Andrew Weickhardt, MD, senior clinical fellow at the CU Cancer Center. "In nearly half of patients, when these drugs stop working, they stop working only in a limited number of sites. Given how well these people tolerate the medication, it made sense to us to treat these isolated spots with radiation (or in one case, surgery), and continue the same drug, which was obviously working elsewhere."

This study of 65 patients showed that continuing either crizotinib or erlotinib after the treatment of resistant pockets was associated with more than half a year of additional .

The benefit was especially robust when the metastatic lung cancer progressed in the brain. The brain is unfortunately a common site of progression because the molecules of crizotinib and erlotinib have difficulty in passing from the bloodstream into the brain, across the so-called blood-brain barrier. sit in the brain as in a robber's cave, hidden away from the drugs.

"We expect using radiation to zap these pockets of cancer in the brain, and then continuing the targeted therapy to become the standard of care," says CU Cancer Center investigator, Ross Camidge, MD, PhD, director of the thoracic oncology clinical program at University of Colorado Hospital.

There was also a smaller but still significant progression-free survival benefit for using this approach in patients whose cancers progressed first outside the brain.

If and when pockets of crizotinib- or erlotinib-resistant lung cancer are detected, "Clinicians should consider using radiation in the body and especially in the brain to weed the garden while continuing the drug, when there is good ongoing control of the cancer in other sites in the body," Weickhardt says.

Explore further: Study shows different approach after progression in non-small cell lung cancer patients

Related Stories

Study shows different approach after progression in non-small cell lung cancer patients

November 15, 2012
Right now, the best known treatment for patients with metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase gene rearrangements (ALK) or epidermal growth factor receptor mutations (EGFR) is crizotinib ...

Study examines drug resistance in ALK positive lung cancer

January 19, 2012
Scientists from the University of Colorado Cancer Center have once again advanced the treatment of a specific kind of lung cancer. The team has documented how anaplastic lymphoma kinase (ALK) positive advanced non-small cell ...

Benefit of targeted lung cancer therapy confirmed

June 3, 2011
A drug that targets a specific type of lung cancer shows a dramatic response in more than half of the people who take it. The drug, called crizotinib, has been in clinical trials since 2006, and the results from the largest ...

Crizotinib reduces tumor size in patients with ALK positive lung cancer

September 6, 2012
Crizotinib is effective in shrinking tumors in patients with anaplastic lymphoma receptor tyrosine kinase (ALK) positive non-small cell lung cancer, a cancer commonly found in people who never smoked, and should be the standard ...

First and only therapeutic drug for ALK-positive lung cancer approved

August 31, 2011
In a major triumph for personalized medicine, the FDA approved the drug crizotinib for use with the lung cancer type known as ALK-positive.

Phase III trial shows crizotinib superior to single-agent chemotherapy for ALK-positive lung cancer

September 30, 2012
The results of a new phase III trial show that crizotinib, a targeted therapy, is a more effective treatment than standard chemotherapy for patients with advanced, ALK-positive lung cancer, researchers said at the ESMO 2012 ...

Recommended for you

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.