Pazopanib - Kinase Inhibitor With Promise

Pazopanib hydrochloride has been approved by the US FDA for the treatment of kidney cancer. The drug is marketed in the US under the trade name Votrient®.

Pazopanib hydrochloride was developed by GlaxoSmithKline. The drug, which is administered orally in tablet form, received formal approval from the Food and Drug Administration (FDA) for treating advanced kidney cancer (renal cell carcinoma) in October 2009.

Each year more than 58,000 adults in the United States are diagnosed with renal cell carcinoma (RCC), the most common form of kidney cancer. It is also called conventional or clear cell renal cell carcinoma. This condition is responsible for 85% of all kidney cancers and kills more than 13,000 Americans annually. Slightly more blacks and those of northern European ancestry are susceptible, but no race is immune. About twice as many men as women will contract the disease and the median age is 64. In this country, renal cell cancer is the 10th leading cause of death by cancer in adult males.

While the specific cause of renal cell carcinoma is unknown, its method of operation is understood as are the risk factors that seem to contribute to its development. Cancerous cells take up residence in the lining of the tinier tubules in the kidney. From there, abnormal cells rapidly multiply, eventually forming a mass or tumor that robs surrounding organs and tissues of O2 and vital nutrients. Cells may also break off and float through the bloodstream or lymphatic system. The most common destinations are the lungs, liver, bones and brain, but the colon and pancreas can also be invaded. Survival depends to a great extent on how early the cancerous condition is detected and the amount of metastasis.

FDA approval of pazopanib followed an international, multi-center trial against a placebo (an inactive drug). This was the type of drug trial in which neither the patient nor the treating physician knows if they are being given the test compound or the placebo. A randomized trial ascribes patients from the eligible pool (for each stage of a study) to the placebo or treatment group on a random basis – it is intended to reduce the chances of subjective bias being introduced to the trial.

The study involved two groups of patients with renal cell carcinoma: those who were previously treated with cytokine therapy and a second group which had not. 435 patients were enrolled in the study; of these, 290 received the drug and 190 were given a placebo. The study measured the whether the cancer patients got worse (specificaly the length of time during or after treatment that a patient’s disease does not worsen). Patients receiving pazopanib had a median PFS of 9.2 months compared to 4.2 months for those in the placebo group (irrespective of prior cytokine therapy). At the end of the study period, 40% of the patients that had participated in the trial had died. However, the response rate (the percentage that showed a partial or a total remission of their cancer) for patients treated with pazopanib was 30%. This figure was 3% for those patients who had received a placebo. In this study, scientists measured how long the tumor shrank before it began to grow again - the so-called "duration of response". The median duration in this study was 13.5 months.

According to the FDA report, the two groups had statistically different rates of adverse reactions. The adverse reactions included abnormal liver function, high blood pressure, diarrhea, and too much protein in the urine. Cardiac issues - as measured by altered EEG readings - have been reported with pazopanib. This type of reaction happens with some other drugs, too.

The report notes that two deaths in the study were associated with liver failure. As a consequence of this, Pazopanib's official product label warns about possible hepatic dysfunction. For this reason FDA advises that liver function tests be conducted every month at the start of treatment and periodically thereafter. In patients with a history of liver problems, or abnormal results, the manufacturer provides recommendations for dose modification. The FDA also recommends that doctors monitor heart function and electrolytes during treatment.



pazopanib molecule

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