A phase III clinical trial has shown that Lapatinib ( Tykerb ) slows cancer growth and improves survival in a subset of patients with an advanced renal cell carcinoma ( RCC ) that continued to grow despite standard therapy.
The patients in the study who responded favorably to this drug had tumors that produced the greatest amounts of epidermal growth factor receptor ( EGFR ), a protein that plays a key role in cell growth and division.
Our findings suggest that Lapatinib could be a new treatment option, along with immunological therapies and anti-angiogenesis agents, for patients with advanced renal cell carcinoma that produces high levels of EGFR, said lead author Alain Ravaud, at University Hospital of Bordeaux and the University Victor Ségalen in Bordeaux, France.
Although Interleukin-2 and Interferon-alpha are the standard treatments for patients with advanced renal cell carcinoma, only about 15% of patients respond to these immunotherapies.
FDA ( Food and Drug Administration ) has recently approved Sunitinib ( Sutent ) and Sorafenib ( Nexavar ) for treating renal cell carcinoma. Both target enzymes involved in angiogenesis.
Lapatinib inhibits two tyrosine kinase enzymes. These enzymes are part of the EGFR pathway, which is responsible for tumor proliferation and growth, and is found in many types of cancer.
In this study, Lapatinib was compared with hormonal therapy ( Megestrol or Tamoxifen ), which was considered a standard treatment when the trial was designed for patients with renal cell carcinoma that persists despite immunotherapy.
Starting in December 2002, 207 patients with advanced renal cell carcinoma that continued to grow despite treatment with immunotherapy were randomly assigned to receive hormonal therapy, and 209 patients were given 1,250 mg of Lapatinib daily for a median duration of 12 weeks.
When the group was analyzed as a whole through September 2005, overall survival and the time to progression did not differ significantly between the two treatment groups.
Since Lapatinib targets the EGFR pathway, the trial was designed to assess patients according to the levels of EGFR produced by their tumors.
Among 241 patients whose tumors produced the highest amounts of EGFR, time to progression was longer in the Lapatinib group ( 15.1 weeks vs. 10.9 weeks for the hormonal therapy group ), as was overall survival ( 46 weeks vs. 37.9 weeks ).
Lapatinib was generally well tolerated; common side effects included rash ( observed in 44% of patients vs. 3% of those on hormonal therapy ) and diarrhea ( 40% vs. 3%; usually minor or moderate ). The patients are continuing to be followed.
Source: 42nd Annual Meeting American Society of Clinical Oncology ( ASCO ), 2006