麻豆传媒

THREE patients with incurable neck and head cancer have survived for three
years after being treated with a combination of chemotherapy and a cold virus
that has been modified to attack tumours.

鈥淎ll these patients were considered no-hopers beforehand,鈥� says Fadlo Khuri,
head of the team that developed the treatment. All three have remained free of
the disease for three years. Patients with head and neck cancer seldom survive
for longer than six months to one year when treated with chemotherapy alone.

Khuri and his colleagues, based at the M. D. Anderson Cancer Center at the
University of Texas in Houston, gave 30 patients cisplatin and
5-fluorouracil鈥攕tandard anticancer drugs. They also administered a virus
that was primed to attack and destroy cancer cells but not healthy ones.

The virus the team chose, called the ONYX-015 adenovirus, normally causes
colds. The Texas team altered the virus so that it couldn鈥檛 replicate in healthy
cells, but could infect and destroy cells that have faulty copies of the gene
p53. This is the gene that normally destroys abnormal cells before they
turn cancerous. Malfunctions in this gene are present in between 45 and 70 per
cent of all head and neck cancers, and it is this defect that enables the cancer
to grow unchecked.

ONYX-015 is ideal for targeting this defect. In its natural state, the common
cold virus knocks out p53 in the cells that it infects. This stops the
cells self-destructing before the cold virus has had time to make millions of
copies of itself.

To protect healthy tissue, Khuri deleted E1B, the gene whose protein
would knock out p53 in normal cells鈥攕o ONYX-015 would only thrive
in cancer cells with defective p53 genes.

In trials, the results were impressive. Injected tumours shrank in 19 of the
30 patients. Eleven of the tumours at least halved in size and eight disappeared
altogether. This is all the more remarkable, says Khuri, because the injected
tumours averaged 10 centimetres in diameter

To test the combination treatment, Khuri chose 11 patients with multiple
tumours. He injected only the largest tumour with the virus and used the smaller
tumours as 鈥渃ontrols鈥�. The virus-treated tumours responded best. Nine of the 11
injected tumours shrank, while only three of the uninjected ones did.

Most of the patients subsequently died from tumours that were too
inaccessible to inject or from other tumours that grew later. However, out of
the 30 patients three remain disease-free.

For their next trial, Khuri and his collaborators in Britain and Canada
intend to select 400 patients whose tumours can all be injected with the
adenovirus. 鈥淚f you look at the big picture, these are very impressive results
for local control of tumours,鈥� says Khuri. 鈥淭he ultimate question, however, is
whether you can translate that into improved survival.鈥�