A Phase III trial administering Nexavar ( Sorafenib ) or placebo in combination with the chemotherapeutic agents Carboplatin and Paclitaxel in patients with advanced melanoma did not meet its primary endpoint of improving progression-free survival.
The treatment effect was comparable in each arm.

Two hundred seventy patients progressing after one previous systemic chemotherapeutic treatment ( with either Dacarbazine or Temozolomide ) were enrolled into the study.

Nexavar is an oral multi-kinase inhibitor that targets both the tumor cell and tumor vasculature.
In preclinical models, Nexavar targeted members of two classes of kinases known to be involved in both cell proliferation and angiogenesis.
These kinases included RAF kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, and FLT-3.

Nexavar is currently approved in a number of countries, including the U.S. and the European Union, for the treatment of patients with advanced kidney cancer.
In addition, Nexavar is being evaluated as a single agent in a Phase III clinical trial for the treatment of advanced hepatocellular carcinoma ( HCC ), or liver cancer, a study that has completed enrollment.
A Phase III clinical trial of Nexavar combined with Carboplatin and Paclitaxel in non-small cell lung cancer ( NSCLC ) for treatment-naive patients was initiated in the first half of 2006.

Based on the current, approved package insert for the treatment of patients with advanced kidney cancer, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed.
Incidence of bleeding regardless of causality was 15 percent for Nexavar vs. 8 percent for placebo, and the incidence of treatment-emergent cardiac ischemia/infarction was 2.9 percent for Nexavar vs. 0.4 percent for placebo.
Gastrointestinal perforation was an uncommon event and has been reported in less than 1% of patients taking Nexavar.
Most common treatment-emergent adverse events with Nexavar were diarrhea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia and nausea.
Grade 3/4 adverse events were 38 percent for Nexavar vs. 28 percent for placebo.
Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding.
In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.

In the United States, the incidence of melanoma has doubled in the last 25 years.
Melanoma accounts for about four percent of skin cancer cases, but is responsible for approximately 77 percent of skin cancer deaths.
In 2006, it is estimated that over 62,000 new cases of melanoma will be diagnosed in the U.S., with close to 8,000 people expected to die from the disease.
Worldwide, it is estimated that about 132,000 people are diagnosed with melanoma and more than 40,000 die from the disease each year.

Source: Onyx Pharmaceuticals, 2006


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