An Alternative When Cancer Grows

Targeted and local therapy may be better than chemotherapy with growing lung cancer

(RxWiki News) When non-small cell lung cancer (NSCLC) grows again after shrinking on targeted therapy, patients may turn to chemotherapy. Adding local therapy to targeted drugs could offer another solution.

Unlike chemotherapy, targeted drugs like kinase inhibitors are designed to attack cancer more specifically and limit damage to healthy cells. Kinases are enzymes that control when cell growth happens.

A new study shows that when cancer becomes resistant to kinase inhibitors, ongoing benefit can still be derived from the drugs when they can be used along with radiation or surgery, focusing on specific parts of the body.

"Ask a doctor about all therapy options."

D. Ross Camidge, MD, PhD, associate professor of medical oncology at the University of Colorado Denver School of Medicine, recently worked on a collaborative effort looking at patients with metastatic EGFR (epidermal growth factor receptor) mutant and ALK (anaplastic lymphoma kinase) positive NSCLC cancers that had spread to many parts of the body, including the brain.

EGFR and ALK are genetic and cellular characteristics of the cancer that allow the cancer to grow, but also help pathologists identify it.

Cancer cells often reproduce uncontrollably, but kinase-inhibiting drugs can prevent this when the cancer is dependent on that particular kinase, or enzyme, such as ALK or EGFR. In some individuals, these drugs can be highly effective but, after a while, the cancer inevitably progresses.

The 51 patients in this study had initially benefited from either crizotinib or erlotinib. Both of these kinase-inhibiting drugs are particularly effective in the subtypes of lung cancer that the patients had, but their cancers had all started to grow again.

The standard treatment option at this point would be to offer the patient some kind of cytotoxic chemotherapy. Side effects can be severe as chemotherapy can broadly affect both cancerous and healthy cells.

Dr. Camidge and his colleagues, however, recognized that in some individuals, not every site of the cancer in their body was progressing. As an alternative, they wanted to see how these patients would respond if they stayed on the kinase inhibitors but received radiation therapy or surgery to try and kill the cancer in the areas where it was growing.

Doctors deemed 25 of the patients suitable for what they called local ablative therapy or LAT—using radiation or surgery. Some of these patients had just progressed in the brain and some had just progressed in isolated areas in the body, for example in one lymph node or one adrenal gland.

On average, among those considered suitable for LAT, it took 9.8 months before the cancer first progressed. After radiation or surgery, further cancer progression was halted for an average of 6.2 more months.

The benefit was most marked in patients who only experienced isolated growth in the brain, where cancer progression may reflect lower levels of the drugs getting into the brain more than anything else. After local therapy, this group had another average of 7.1 months of extra disease control before any further growth could be detected in either the body or the brain.

Dr. Camidge told dailyRx News, “Your disease may respond to the kinase inhibitors, but then a single area may become resistant and start to grow. Therefore, if you delete that area with a local therapy—just like removing a weed from the garden—you can preserve the ongoing benefit elsewhere by keeping the drug going. With this approach, you can push off chemotherapy until a point in time when the balance shifts more in favor of all of the cancer becoming resistant, not just isolated areas. By recognizing that resistance isn’t an all or none phenomenon, this approach may extend the duration of disease control to the maximum using a single tyrosine kinase inhibitor.”

Dr. Camidge added that other work is needed to more clearly define the criteria for when LAT is feasible or not. He also said that methods of cancer surveillance have to be studied further. Using PET scans versus CT scans affects the frequency with which “early stage progression” suitable for LAT can be detected.

“If the cancer is growing in multiple places at the time progression is found, then the cat’s out of the bag and local therapy is much less likely to be appropriate,” said Dr. Camidge.

The study was published in the December 2012 issue of the International Association for the Study of Lung Cancer’s (IASLC) Journal of Thoracic Oncology.

Review Date: 
November 25, 2012