A trial looking at oxaliplatin and 5FU chemotherapy before surgery for cancer of the food pipe

Cancer type:

Oesophageal cancer

Status:

Results

Phase:

Phase 2

This trial looked at oxaliplatin to shrink cancer of the food pipe (also called the oesophagus or gullet) before surgery.

More about this trial

Doctors treat cancer of the food pipe (oesophageal or gullet cancer) with chemotherapy, radiotherapy or surgery.

You have surgery to remove the cancer if the cancer hasn’t spread to other parts of the body (metastasised). You might have chemotherapy before surgery to shrink the cancer. This is neoadjuvant chemotherapy.

For this doctors usually use cisplatin and 5FU. But research had shown that oxaliplatin might be better than cisplatin. It works in the same way as cisplatin but has fewer side effects.

The aims of this trial were to find out:

how oxaliplatin affects the cancer cells
what the side effects are

Summary of results

The team found there was a varied response of oesophageal cancer to oxaliplatin and 5FU.

This was a phase 2 trial.

In this trial, everyone had 2 treatments of oxaliplatin and 5FU before surgery to remove their cancer. Researchers took tissue samples from everyone before and after having chemotherapy.

The team compared the samples from 30 people to see what happened to the genes Open a glossary item in the cancer cells. They found that each cancer was typically made up of a small number of different cell populations (clones). And that chemotherapy could rapidly and strongly affect their genes. This genetic response tended to fall into 3 main groups:

those that appeared not to be affected by treatment and had very small changes in the genes of the cancer cells
those that appeared to have a strong response to chemotherapy (with many gene changes (mutations ) before chemotherapy but only a few afterwards)
a small number of cancers that had many gene changes before chemotherapy, but many different ones afterwards

The researchers say the 2nd group were passing through a ‘genetic bottleneck’. This is where a cancer had many different mutations before treatment, but only a few were left behind afterwards (suggesting most of the cancer had gone).

Normally before surgery doctors use a scan to assess the response of the cancer to chemotherapy (clinical response). And after surgery the cancer tissue that was removed is looked at under a microscope (pathological response). Generally, these ways meet with a good pathological response having a tight bottle neck. But the team found some people in whom it didn’t.

A few people seemed to have a pathological response under the microscope, without a bottle neck. Most importantly, a few people seemed to have a genetic response with a bottleneck but without a pathological response.

As there is a delay between chemotherapy and surgery, all people had a scan (PET-CT Open a glossary item ) after their chemotherapy. For these few people above, the scan suggested a clinical response but by the time the cancer was examined under the microscope there was no response.

This is important, as it suggests that the cancer was responding to the chemotherapy. But part of it was able to grow back quickly after it stopped responding. The research team suggested that extra treatment may be helpful for these people.

Overall, the results suggest that response to chemotherapy is complicated and very difficult to predict. However, it may be better to assess response using tissue samples and scans together:

before starting treatment
during treatment
after treatment

This might allow treatment to become more personalised.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.