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Targeted Therapies Developed to Fight Cancer

An experienced doctor who has treated many cancer patients said he is reluctant to prescribe continuous chemotherapy.

 

Chemotherapy should be used as the last resort, claims Xu Jianming, who works at the Cancer Center of the People's Liberation Army's No 307 Hospital based in Beijing.

 

"Chemotherapy can only help 30 to 40 percent of patients reduce the size of their tumors at the beginning," Xu said. "But after about two or three cycles of chemotherapy, 95 percent of them may not see any further improvement," he said.

 

"According to international common practice, each patient has to undergo six cycles of chemotherapy, which is an extremely painful experience," Xu said.

 

Over the years, Xu and many like-minded doctors and researchers from around the globe have been trying to work on the new concept of targeted therapy.

 

Traditional chemotherapies kill both cancer and normal cells. But initial research shows that targeted therapy differentiates between the two and works to inhibit the growth of cancer cells.

 

Today, scientists take three major approaches in targeted therapy research.

 

Molecular biologists study small molecules that can enter cancer cells and disrupt their functions, causing the virulent cells to die.

 

Others utilize molecules that target specific receptors on the surface of the cancer cells or vascular endothelial cells to inhibit growth, also known as monoclonal antibodies.

 

The remaining group of researchers, including Li Jin, professor of Fudan University Cancer Hospital in Shanghai, carry out experiments to target immune cells at tumor cells.

 

"The vaccine we are working on is like a platform. It is expected to treat different cancers if sensitized with different tumor antigens," said Li, who started the research two years ago.

 

Li said he and his colleagues are currently focusing on treating cervical cancer, having already completed studies on mice.

 

"We carried out two experiments, one on vaccination, the other on treatment," he said.

 

In the first trial, the researchers injected vaccines into the mice before introducing into them cervical cancer cells.

 

The order was reversed in the other.

 

Months passed before the results could be seen. But Li and his team were exhilarated as all cervical tumors in the mice were killed by the vaccine.

 

"We are satisfied with the initial conclusion," Li said.

 

They have applied to the State Food and Drug Administration for clinical experiments.

 

"The first sessions may start at the end of this year, with 10 to 20 patients recruited," he said.

 

Compared with Li's early-stage experiments, Professor Xu claims that he has gone a little further in his cooperative research with Professor Angelo Paradiso from Italy's National Cancer Institute.

 

In August, a joint cancer research group led by Xu and Paradiso announced they had made a new discovery about the use of Iressa, a new targeted drug which combats the epidermal growth factor receptor (EGFR), in the treatment of lung cancer patients.

 

"We concluded that it should be used as an optimizer to safeguard the effects of chemotherapy, which means doctors are advised to apply it after multi-cycle chemotherapy instead of in combination with it," Xu said.

 

According to the US Food and Drug Administration, which approved the clinical use of Iressa early this year, the drug is a new anti-cancer drug that inhibits an enzyme present in lung cancer cells, as well as other cancers and normal tissues, that appears to be important to the growth of cancer cells.

 

Iressa is used as a single agent in the treatment of non-small cell lung cancer (NSCLC) that has progressed after, or failed to respond to, two other types of chemotherapy.

 

During their clinical experiments, Xu and his colleagues found more than 20 percent of the 80 studied patients were improving faster, and 50 to 60 percent had their conditions stabilized.

 

And the group expands their conclusion to all such EGFR inhibitors like Iressa -- "sequential EGFR inhibition after chemotherapy could enhance or maintain chemotherapy induced cell damage," Xu and Paradiso wrote in their latest report.

 

The two began cooperative research on Iressa three years ago. They discovered that, despite the pronounced miracle effects of Iressa, no more than 20 percent of the patients actually benefited from it, since Iressa was usually administered along with other drugs, Xu said.

 

Xu used a 45-year-old man with advanced non-small-cell lung cancer as an example.

 

Having gone through six cycles of chemotherapy, the patient was in a stable condition.

 

Then he took Iressa together with chemotherapy drugs for another 86 days.

 

The tumor did not respond to the combination treatment but nor did it grow.

 

"When we find the two therapies are not working in combination, we should understand that we are going in the wrong direction," Xu said.

 

"The patient was so weak when he came to us. We decided to use Iressa alone," Xu said.

 

"After 30 days, his tumor made a minor response and became a bit smaller. And this has been going on for three months."

 

Xu emphasized that his American and European colleagues have also made similar findings.

 

Also, compared with chemotherapy, Iressa has less side effects, he said. Around 30 percent of patients may develop a rash.

 

According to the cancer expert, about 80 percent of the studied patients have extended and improved their lives. This means the chemotherapy guildlines for advanced cancer patients could be modified with such a treatment.

 

Xu said he and his Chinese and Italian colleagues will continue to study the mutations of appropriate cancer cell inhibitors in order to predict the clinical response of Iressa for cancer patients.

 

Xu is also working with many other domestic experts on another new treatment program, which attempts to treat advanced gastric and esophageal cancers. The new program revolves around the combined application of four new chemotherapy medicines.

 

"An initial small trial of 15 patients turned out to be very promising, since 80 percent of them showed positive signs," Xu said.

 

Xu said he and his colleagues must work harder as the Chinese have the highest mortality rate of gastric and esophageal cancers in the world. And colorectal cancer is also proving to be a major life threatener in China.

 

(China Daily November 3, 2004)

 

              

 

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