Clinical insight improves treatment with crizotinib
Treatment with ALK inhibitor - crizotinib requires monitoring of testosterone levels
Men experience a marked drop in their testosterone levels when taking a targeted therapy - crizotinib, to control anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC). That's according to a University of Colorado Cancer Center study published in the April issue of Cancer. Investigators looked at the hormone levels, after a 35-year-old man on the drug reported symptoms that are often attributed to low testosterone levels: fatigue and sexual disinterest.
Listening to the specific issue
Crizotinib tablets were licensed by the USA Food and Drug Administration in August 2011, because of its dramatic and long-lasting suppression of ALK positive NSCLC. ALK positive lung cancer was only recently described, so very few cancer centres have a lot of experience identifying and treating this subtype of the disease. University of Colorado Cancer Center was involved in the initial development of the drug and has treated one of the largest groups of ALK positive patients in the world.
The testosterone study included 19 men with NSCLC taking crizotinib and 19 men with lung cancer receiving other kinds of therapy. According to Dr Andrew Weickhardt, senior clinical fellow, and one of the study's co-authors, when the team started to track testosterone levels over time, they clearly saw a drop within days of starting on the drug, and while testosterone was low in only about 30% of men on other therapies, it was low in all of the men who were on crizotinib.
Spotting patterns and making advances that can improve how someone with lung cancer feels on a daily basis
As men may stay on crizotinib for months, or even years, the effects of low testosterone could be profound. Low testosterone can reduce bone density and muscle strength as well decrease sex drive and increase fatigue and depression. There are many factors associated with a cancer diagnosis that can lower testosterone, but according to endocrinologist, Dr Micol Rothman, co-author of the study, the levels in crizotinib-treated patients were so uniformly low and their direct relationship with starting the therapy meant there was no doubt the drug was contributing to it. Fortunately, this condition can be easily tested for and treated by testosterone supplements.
In recent weeks, several studies from the University of Colorado Cancer Center have advanced understanding about ALK positive NSCLC. One study published in Clinical Cancer Research, reveals that when ALK positive lung cancer eventually mutates to become resistant to crizotinib it does so in different ways. Either the cancer changes the ALK protein so that the crizotinib is ineffective against it or it develops another type of cancer molecule that makes the cancer less dependent on ALK. If the ALK protein changes, it may be vulnerable to a stronger ALK inhibitor. If it combines with another type of cancer molecule, a combination of drugs may be required.
The University of Colorado Cancer Center’s Thoracic Oncology Programme is world renowned for its pioneering treatment of lung cancer. The programme includes a multidisciplinary team of specialists and subspecialists working together to establish the best treatment plan for each patient. Advanced molecular profiling of a patient's tumour, combined with an extensive array of standard and experimental treatments available through clinical trials has lead to major advances in patient outcomes in the last few years. It is the lead site for the Lung Cancer Mutation Consortium, the collaboration of 14 of elite lung cancer programmes in USA. The consortium is profiling ten different molecular abnormalities in lung cancer and pairing them with specific experimental treatments over the next few years.
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