AS1404 (Dimethylxanthenone acetic acid?) - trial - locally advanced or metastatic NSCLC


Lung cancer drug 'extends life'
Lung cancer x-ray (Simon Fraser/Science Photo Library)
Lung cancer prognosis can be poor
An experimental lung cancer drug has extended patients' life expectancy by
more than 50% in preliminary trials.

Patients given the drug AS1404 on top of standard chemotherapy lived an
average of 14 months compared with 8.8 months if given chemotherapy alone.

The phase two study, by UK biotech company Antisoma, looked at 70 patients
with non-small cell lung cancer, the most common form of the disease.

It kills more than 26,000 people in Britain each year.

Survival is the gold standard by which cancer drugs are judged, and this
news is therefore very exciting
Glyn Edwards

The drug belongs to a new class of compounds called vascular disrupting
agents, which work by cutting off the blood supply to tumours.

Solid tumours rely on a network of blood vessels to survive and grow.

AS1404 is able to distinguish between blood vessels feeding the tumour and
those serving healthy organs.

The tumour vessels are more permeable and less well organised than those
of healthy tissue.

Dr Mark McKeage, from the University of Auckland in New Zealand, who
co-led the trial, said: "It is great to see this large survival benefit
with AS1404 in lung cancer patients.

"This makes me feel very optimistic as we proceed into phase three
testing."

Glyn Edwards, chief executive officer of Antisoma, said: "Survival is the
gold standard by which cancer drugs are judged, and this news is therefore
very exciting."

AS1404 was developed by scientists in New Zealand but the pharmaceutical
company it was initially licensed to did not have the resources to develop
it further.

The charity Cancer Research UK stepped in to take the drug into
early-stage clinical trials.

Phase two trials are carried out to see whether the drug or treatment is
effective for treating cancer.

A phase three trial directly compares the new treatment with standard
treatments to see if the new treatment is better.
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http://patient.cancerconsultants.com/news.aspx?id=35189
Addition of AS1404 to Chemotherapy Stalls Lung Cancer Progression

According to preliminary results from a recent phase II clinical trial,
the addition of the vascular disrupting agent AS1404 to standard
chemotherapy reduces the risk of cancer progression in patients with lung
cancer more effectively than chemotherapy alone.

Lung cancer is the most common cause of cancer-related deaths in the
world. Within the US, lung cancer claims more lives each year than breast,
colon, and prostate cancers combined. Non-small cell lung cancer (NSCLC)
is the most common type of lung cancer, accounting for approximately
75%-80% of all lung cancers. NSCLC refers to the type of cell within the
lung where the cancer originates.

Locally advanced or metastatic lung cancer is cancer that has spread from
the lung to different sites in the body. Standard treatment for locally
advanced or metastatic NSCLC typically includes chemotherapy. However, due
to the poor outcomes following standard therapeutic approaches,
researchers are focusing on novel treatments to improve survival duration
for this disease.

AS1404 is an agent that is still in clinical trials. It is referred to as
a vascular disrupting agent. It fights cancer by attacking blood vessels
that transport nutrients to cancer cells.

Researchers recently conducted a clinical trial to directly compare AS1404
plus chemotherapy to chemotherapy alone in the treatment of locally
advanced or metastatic NSCLC. This trial included 71 patients; results
from 47 patients are available at present. Patients were treated with
either AS1404 plus the chemotherapy agents paclitaxel (Taxol®) and
carboplatin (Paraplatin®) or the same chemotherapy regimen without AS1404.

Overall, patients treated with AS1404 had improved outcomes compared to
those treated with chemotherapy alone:

* A partial disappearance of cancer occurred in 43.5% of patients
treated with AS1404, compared with 33.3% treated with chemotherapy only.
* Disease was stabilized in nearly 48% of patients treated with
AS1404, compared with only 33.3% treated with chemotherapy alone.
* Progressive disease occurred in only 8.7% of patients treated with
AS1404, compared with 33.3% treated with chemotherapy alone.
* Side effects were similar between the two groups of patients.

The researchers concluded that, although preliminary, these results
indicate an improvement in anticancer activity with the addition of AS1404
to chemotherapy compared to chemotherapy alone in patients with locally
advanced or metastatic NSCLC.

Longer follow-up is needed to determine if these results will lead to
improved survival for these patients.

Patients diagnosed with NSCLC may wish to speak with their physician
regarding individual risks and benefits of participating in a clinical
trial further evaluating AS1404 or other novel therapeutic approaches. Two
sources of information regarding ongoing clinical trials include the
National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com.

Reference: Antisoma. Antisoma announces promising preliminary phase II
data for AS1404 in lung cancer. Available at:
http://www.antisoma.co.uk/admin/data/datFiles/17_oct_2005.asp. Accessed
October 2005.

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