FDA approves GlaxoSmithKline’s Votrient™ for advanced renal cell cancer

GlaxoSmithKline [NYSE: GSK] announced that the U.S. Food and Drug Administration (FDA) has approved Votrient™ (pazopanib) to treat patients with advanced renal cell carcinoma (RCC), a form of kidney cancer. Approximately 57,700 people in the U.S. will be diagnosed with kidney cancer this year, and 13,000 people will die from this disease.

“RCC is the most common malignancy of the kidney and is highly resistant to chemotherapy,” said Paolo Paoletti, MD, Senior Vice President, GlaxoSmithKline Oncology R&D Unit. “While treatment has improved in the past few years with the introduction of targeted therapies, advanced RCC remains a challenging disease. Votrient will join existing targeted therapies toprovide physicians with a new oral treatment option to their patients with advanced renal cell cancer.”

Votrient, a once-daily, oral medication, is an angiogenesis inhibitor which may help prevent the growth of new blood vessels, thereby blocking the growth of kidney cancer tumors that need blood vessels to survive.

The approval of Votrient was supported by a unanimous decision by the FDA’s Oncology Drugs Advisory Committee (ODAC) that the benefit-to-risk profile for Votrient is acceptable for patients with advanced kidney cancer. The ODAC reviewed data from a Phase III clinical trial showing that Votrient reduced the risk of tumor progression or death by 54 percent compared to placebo, regardless of prior treatment.

In this Phase III trial, the overall median PFS was 9.2 months with pazopanib and 4.2 months with placebo. Treatment-naïve patients who received Votrient experienced 11.1 months of median progression-free survival (PFS) versus 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with Votrient versus 4.2 months with placebo.

The most common adverse events occurring in ≥20% of subjects treated with Votrient included diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. Grade 3/4 adverse events among these toxicities that differed by≥2% included abnormal liver function, hypertension, diarrhea, asthenia, and abdominal pain. Laboratory abnormalities occurring in >10% of patients and more commonly (>5%) in the pazopanib arm included increased transaminases, hyperglycemia, leukopenia, hyperbilirubinemia, neutropenia, hypophosphatemia, thrombocytopenia, lymphocytopenia, hyponatremia, hypomagnesemia, and hypoglycemia. Drug-related deaths were observed in 1.4% of 290 patients and included hepatic failure (n=2), stroke (n=1), and perforation (n=1). Hepatic dysfunction is included as a boxed warning in the product label. Other Warnings and Precautions in the label relate to QT prolongation and torsade de pointes, hemorrhagic events, arterial thrombotic events, gastrointestinal perforation and fistula, hypertension, impaired wound healing, hypothyroidism, proteinuria, and pregnancy.

Votrient has a broad clinical program across multiple tumor types, with study details available at www.clinicaltrials.gov. More than 2,000 patients have been treated to date in clinical trials. Votrient is not yet approved in any country other than the U.S.

Votrient™ is the proposed registered trademark to be used in the United States and Europe.

Vorinostat Reduces Formation of Brain Metastases in Mice

The drug vorinostat is able to cross the blood-brain barrier and reduce the development of large metastatic tumors in mice brains by 62 percent when compared to mice that did not receive the drug, according to a new study. In humans, the drug has been approved by the U.S. Food and Drug Administration for the treatment of a cancer called cutaneous T-cell lymphoma but can be used experimentally to study its effectiveness against other cancers. This research, by investigators at the National Cancer Institute (NCI) and their collaborators, appears online in Clinical Cancer Research.

For people, while various therapies are improving the survival of breast cancer patients, the incidence of breast cancer spreading to the brain is increasing. Brain metastases of breast cancer have proven to be largely untreatable because the blood-brain barrier, which arises from the specialized structure of blood capillaries in the brain, severely limits drug access and many drugs are actively transported out of brain at this barrier. Consequently, the one-year survival estimate for breast cancer patients after a diagnosis of brain metastasis is only about 20 percent.

Vorinostat has been found to slow the growth of primary tumors of several different types of cancer in mice. Previous studies have suggested that the drug can be taken up by the brain, although little was known about its effects on metastatic tumors. Therefore, to study the effect of vorinostat on the formation of brain metastases, scientists used a mouse model of human breast cancer. Human breast cells were cultured in the laboratory and were injected into mice with compromised immune systems. The breast cancer cells then migrated to the brain, forming metastases. "Drugs that can cross the blood-brain barrier and reduce the size and incidence of metastatic tumors are urgently needed," said Patricia S. Steeg, Ph.D., study author, Center for Cancer Research, NCI. The researchers found that vorinostat was absorbed readily into normal mouse brains, and accumulation of the drug was up to three-fold higher in some metastases treated with this drug when compared to surrounding brain tissue. Vorinostat also reduced the development of tiny tumors (micrometastases) in mice by 28 percent when compared with mice that did not receive this therapy.

www.nci.nih.gov

3.2 Million Europeans Are Diagnosed With Cancer Every Year

Every year 3.2 million Europeans are diagnosed with cancer, mostly breast, colorectal or lung cancers, according to European Commission report. In 2006 in Europe, there were an estimated 3 191 600 cancer cases diagnosed (excluding nonmelanoma skin cancers) and 1 703 000 deaths from cancer. The most common form of cancers was breast cancer (429 900 cases, 13.5% of all cancer cases), followed by colorectal cancers (412 900, 12.9%) and lung cancer (386 300, 12.1%). Lung cancer, with an estimated 334 800 deaths (19.7% of total), was the most common cause of death from cancer, followed by colorectal (207 400 deaths), breast (131 900) and stomach (118 200) cancers, according to European Society for Medical Oncology. Breast cancer is the leading cause of death from cancer in women in Europe. A fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies. These declines have been attributed to the combined effect of earlier detection and improving treatment, but it was observed mainly in young women, and because of the ageing of the European population the number of deaths from breast cancer is still rising (130 000 in 2004, 132 000 in 2006).

Excess body weight causes over 124,000 new cancers a year

At least 124,000 new cancers in 2008 in Europe may have been caused by excess body weight, according to estimates from a new modelling study. The proportion of cases of new cancers attributable to a body mass index of 25kg/m² or more were highest among women and in central European countries such as the Czech Republic, Latvia, Slovenia and Bulgaria. “As more people stop smoking and fewer women take hormone replacement therapy, it is possible that obesity may become the biggest attributable cause of cancer in women within the next decade”, Dr Andrew Renehan, the lead author of the study, said.
Dr Renehan, who is a senior lecturer in cancer studies and surgery at the University of Manchester (UK), and his colleagues in the UK, The Netherlands and Switzerland, created a sophisticated model to estimate the proportion of cancers that could be attributed to excess body weight in 30 European countries. Using data from a number of sources including the World Health Organisation and the International Agency for Research on Cancer, they estimated that in 2002 (the most recent year for which there are reliable statistics on cancer incidence in Europe) there had been over 70,000 new cases of cancer attributable to excess BMI out of a total of nearly 2.2 million new diagnoses across the 30 European countries. Then, the researchers projected the figures forward to 2008, taking into account what was known about shifts in the distribution of BMI, the dramatic decline in women’s use of hormone replacement therapy (HRT) from 2002 onwards following research that showed it increased the risk of breast cancer, and the wider use of PSA screening for prostate cancer in men.

They found that the number of cancers that could be attributed to excess body weight increased to 124,050 in 2008. In men, 3.2% of new cancers could be attributed to being overweight or obese and in women it was 8.6%. The largest number of obesity-related new cancers was for endometrial cancer (33,421), post-menopausal breast cancer (27,770) and colorectal cancer (23,730). These three accounted for 65% of all cancers attributable to excess BMI.

The number of new cases of obesity-related oesophageal cancer was particularly high in the UK relative to the rest of Europe. “This country accounts for 54% of new cases across all 30 countries,” said Dr Renehan. “This may be due to synergistic interactions between smoking, alcohol, excess body weight and acid reflux – and is currently an area where research is required.”

The Dangerous Gas in Your Home: Radon Can Cause Cancer

Radon, a gas thas has no smell, colour or taste, is estimated to cause between 3% and 14% of all lung cancers, according to World Health Organisation. This chemically gas is much more likely to cause lung cancer in people who smoke and is the primary cause of lung cancer among non-smokers. In most cases, the greatest exposure to radon comes from the home. This dangerous gas is produced from the natural radioactive decay of uranium, which is found in rocks and soil. Unfortunately, radon can also be found in water.

Though, radon levels in homes can be reduced by improving the ventilation of the house, sealing floors and walls, installing a positive pressurization or ventilation system.

Read more: http://www.who.int/mediacentre/factsheets/fs291/en/index.html