Protein test on lung cancer cells predicts who will benefit from chemo

Sep 7 2006

European researchers say a test can predict whether chemotherapy will help patients with lung cancer live longer after surgery.

It seems the presence or absence of the protein ERCC1 in lung cancer cells can help doctors decide which patients can benefit from a type of chemotherapy before treatment starts.

The new study involved 28 medical centers in 14 countries, and looked at non-small-cell lung cancer, which makes up about 87 percent of all lung cancer cases.

The researchers were eager to discover if there was a more precise way to predict who would benefit from chemotherapy and focused on ERCC1 because it is involved in repairing the tumour DNA that chemotherapy aims to destroy.

For the study, University of Paris researchers Ken A. Olaussen, PhD; Jean-Charles Soria, MD, PhD; and colleagues collected 761 tumour samples and analyzed data from a very large clinical trial looking at whether post-surgery chemo improved survival for non-small-cell lung cancer patients; they found it only did so for about 4% of patients.

Less than half, (44%), carried a protein called ERCC1; the other 56% did not.

ERCC1 has been a suspect in chemotherapy resistance because it repairs DNA and platinum-based chemotherapy works by disrupting the cancer's DNA.

Volunteers with undetectable levels of the protein ERCC1, which is important in repairing DNA, had a five-year survival rate of 47 percent when treated with the platinum-based class of chemotherapy drugs such as cisplatin.

The survival rate dropped to 39 percent without treatment after surgery to remove the tumour.

When the tumours had plenty of ERCC1, the situation was reversed and those who received no chemotherapy did better than those who did.

The survival rate was 46 percent for untreated patients, compared with 40 percent for those who got cisplatin.

The team, led by Ken Olaussen of the University of Paris say a low level of expression of ERCC1 by tumour cells was associated with longer survival following cisplatin-based chemotherapy.

Lung cancer tumours are the commonest form of cancer and affect over 174,000 people in the United States each year, killing 162,000 of them.

The majority are caused by smoking.

Of the 426 people with undetectable levels of the ERCC1 protein, average survival was 56 months if they received chemotherapy and 42 months if they did not.

When ERCC1 was present in the tumours, the 170 patients who received no additional treatment after their surgery typically survived 55 months, compared with 50 months for the 165 who received cisplatin.

While the study was conducted in lung cancer patients, Olaussen and colleagues say that ERCC1 has been linked to chemo resistance in patients with other kinds of cancer, including stomach, ovarian, colon, and esophageal cancers.