(RxWiki News) In 2011, the US Food and Drug Administration fast-tracked the approval of Xalkori (crizotinib) to treat a specific type of non-small cell lung cancer (NSCLC). Since its approval, side effects have been discovered.
Clinicians have found that Xalkori appeared to reduce kidney function as measured by a commonly used test.
Kidney function was restored either totally or to within 85 percent of previous function once the medication was stopped.
What’s not clear is whether this side effect had to do with the medication or was a reflection of the accuracy of the test being used to measure kidney function, the authors of a new study said.
"Tell your doctor if you notice any unusual side effects after starting a new medication."
Ross Camidge, MD, PhD, director of the thoracic oncology clinical program at the University of Colorado Cancer Center, led this study. Senior author Evelyn Brosnan, MD, was a final year medical student mentored by Dr. Camidge when the research was being conducted.
NSCLC is the most common form of lung cancer, making up 84 percent of all cases. Up to 7 percent of NSCLC is driven by an anaplastic lymphoma kinase (ALK).
Xalkori was approved by the FDA under its accelerated approval process because the medication more than doubled the progression-free survival (time during which the cancer does not progress) of patients with this ALK-positive lung cancer.
Studies leading to its approval showed that the most common side effects of Xalkori were nausea, diarrhea, vomiting, constipation, visual disturbances and fatigue. More serious side effects include lowering of white blood cell counts, liver damage and lower than normal levels phosphate in the blood.
Since its approval, Xalkori's side effects have been identified. These side effects include lowered testosterone levels in about 84 percent of men who take the medication, lowered heartbeat and acute interstitial lung disease, which affects the air sacs of the lungs.
For this study, 38 pateints with stage IV ALK-positive NSCLC were given a blood test called creatinine to evaluate kidney function before, during and after treatment with Xalkori. The blood test provided an estimated glomerular filtration rate (eGFR) — a measure of how well the kidneys filter blood.
The average eGFR fell by 23.9 percent after starting the medication, with the majority seeing the decline within two weeks of starting Xalkori.
There was complete follow-up data for 16 patients. After stopping the medication, 56.3 percent of these patients saw kidney function restored to pre-medication (baseline) levels and the other 43.6 percent recovered with 84-97 percent of baseline eGFR.
Exactly how the medication was causing this effect is not clear. Evidence suggests, according to the researchers, that the medication was not causing any significant permanent kidney damage.
“... [I]f a patient’s creatinine seems to heading into some kind of danger zone on crizotinib, and a doctor is considering altering their management of the patient, we would strongly recommend reassessing kidney function through a second, non-creatinine based, method before making any final decision," Dr. Camidge said in a statement.
“As anti-cancer drugs enter the pharmacy quicker and quicker, we have to empower the hundreds and thousands of doctors out there to believe in what they might see in their clinics and report things, leveraging all that experience for the greater good. In the cases of altered measures of kidney function and lowered testosterone with crizotinib, once we notice these side-effects and get the word out, patients can be much more appropriately managed," Dr. Camidge said.
This study was published in the Novemer issue of the journal Cancer.
Dr. Camidge and another author disclosed having financial relationships with Pfizer, the maker of Xalkori.