Promising Results For New Kidney Cancer Drug

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Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials;  Urology / Nephrology
Article Date: 30 Oct 2007 - 2:00 PDT

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A phase II trial on axitinib, a new experimental drug for treating patients with cytokine-refractory, metastatic kidney cancer who have a poor response to more traditional drugs has shown promising results according to a new study published in the The Lancet Oncology.

Professor Olivier Rixe of the University of Paris, France, and colleagues assessed the activity and safety of axitinib in a group of patients with metastatic renal-cell cancer who had failed to respond to cytokine-based treatments.

The researchers enrolled 52 patients between October 2003 and April 2004. Each patient had at least one measurable lesion that could be targeted and was given an oral dose of axitinib starting at 5 mg twice a day.

Rixe and colleagues assessed the percentage of patients who responded either completely or partially using the Response Evaluation Criteria In Solid Tumors (RECIST) method, as well as how long they took to respond, the time to progression, overall survival, safety and other measures.

In an intention to treat analysis, the study produced the following results:

• Of the 52 patients, 2 responded completely and 21 partially.


• This equated to an objective response rate of 44.2 per cent.


• The median response rate was 23.0 months (range 4.2 to 29.8 months).


• But 12 of 23 initial responders progressed with response durations of 4.2 to 26.5 months.


• Also, 22 patients showed stable disease for more than 8 weeks, with 13 of them for 24 weeks or more.


• 4 patients had early disease progression, 3 had missing response data.


• Median time to progression was 15.7 months (range 0.03 to 31.5 months).


• Median overall survival was 29·9 months (range 2·4 to 35·8 months).


• Adverse events linked to treatment included diarrhoea, hypertension, fatigue, nausea, and hoarseness.


• High blood pressure was found in 30 patients.


• Of these, all but 8 responded to blood pressure treatment. 7 of the 8 had a history of high blood pressure at enrollment.

The researchers concluded that:

"Axitinib shows clinical activity in patients with cytokine-refractory metastatic renal-cell cancer. Although 28 patients had grade 3 or grade 4 treatment-related adverse events, these adverse events were generally manageable and controlled by dose modification or supportive care, or both. Further studies are needed to confirm these findings."

Kidney cancer is the sixth leading cause of cancer deaths in the US, and thought to be responsible for nearly 13,000 deaths a year. Kidney cancer is actually a range of cancers, each with a different histology or tissue characteristics. Each type of kidney cancer also develops differently and needs different kinds of treatment.

The most common type of kidney cancer is clear-cell renal cancer, found in 75 per cent of kidney cancer patients.

There are few treatment options for kidney cancer and most patients die. Even with chemotherapy, hormone or biological therapy with the latest targeted drugs, the survival rate is rarely more than 10 per cent.

Axitinib is a selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. By selectively targeting a single growth factor receptor pathway, treatments with this drug could provide a way to adjust dosage and combine with other drugs aimed at specific parts of the pathway. This would potentially minimise toxicity as well as optimise therapeutic outcomes suggested the researchers.

Rixie said that although a randomized controlled trial was now needed:

"The objective response and time to progression in our study suggest that axitinib might be a promising drug in the treatment of patients with metastatic renal-cell cancer."

In an accompanying article in the same issue of the journal, Dr W Marston Linehan of the US National Cancer Institute, said that these findings "suggest that a drug such as axitinib has promise as a second-line treatment in cytokine-refractory metastatic renal-cell carcinoma, and might have potential as first-line treatment or in combination with other agents targeting the Von Hippel-Lindau pathway (or both)."

"Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study."
Olivier Rixe, Ronald M Bukowski, M Dror Michaelson, George Wilding, Gary R Hudes, Oliver Bolte, Robert J Motzer, Paul Bycott, Katherine F Liau, James Freddo, Peter C Trask, Sinil Kim and Brian I Rini.
Available online 25 October 2007.
Lancet Oncology 2007; 8:975-984.
doi:10.1016/S1470-2045(07)70285-1.

Click here for Abstract.

Written by: Catharine Paddock
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