Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Pancreatic Cancer Home Page 2 NCI's gateway for information about pancreatic cancer. Highlights from ASCO 2005 3 A collection of links to material summarizing some of the important clinical trial results announced at the 2005 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Pancreatic cancer, erlotinib"> (Tarceva®), targeted therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

Patients with advanced pancreatic cancer who were treated with the drug erlotinib (Tarceva®) in addition to a standard drug, gemcitabine, had modest improvement in one-year survival rates compared to patients treated with gemcitabine alone. However, it is too soon to add erlotinib to standard therapy for all patients with advanced pancreatic cancer.

Source

American Society of Clinical Oncology annual meeting, Orlando, Florida, May 14, 2005.

Background

Survival rates for patients with pancreatic cancer are extremely poor. The disease is often resistant to chemotherapy and radiation therapy and tends to spread quickly to other parts of the body. Only four percent of all patients are alive five years after a diagnosis of pancreatic cancer. Only about 15 percent of patients whose tumors are small and detected early (before the tumor has spread beyond the pancreas) survive five years. Unfortunately, fewer than one in five tumors are detected at this early stage. Most patients do not have specific symptoms until the disease is advanced.

Since 1997, chemotherapy with the drug gemcitabine has been a standard treatment option for patients with advanced pancreatic cancer that cannot be removed by surgery. In a phase III trial, 18 percent of patients treated with gemcitabine survived for one year, compared with two percent of patients treated with another drug called 5-fluorouracil (5-FU).

Erlotinib is a new drug that was developed to block signals that stimulate cancer cells to grow and multiply. It is thought that erlotinib does this, in part at least, by inhibiting an enzyme associated with a protein called epidermal growth factor receptor (EGFR), which stimulates cells to divide. Pancreatic cancer cells frequently have abnormally high levels of EGFR.

The Study

The current study involved 569 patients with advanced pancreatic cancer that could not be removed by surgery. The patients were assigned at random to treatment with gemcitabine plus either erlotinib or a placebo (dummy pill).

All patients were tested to find out whether their tumors had abnormally high levels of the EGFR protein, though patients were enrolled regardless of their EGFR levels.

The research team that conducted the international study was led by Malcolm J. Moore, M.D., of Princess Margaret Hospital in Toronto, Canada. The results were initially announced in January 2005 at the American Society of Clinical Oncology’s Gastrointestinal Cancer Symposium.

Results

Twenty-four percent of patients treated with gemcitabine and erlotinib, compared with 17 percent of those treated with gemcitabine and a placebo, were alive after one year. However, the median difference in survival between the two groups was less than one month (6.4 months for the erlotinib group, compared with 5.9 months for the placebo group).

In this study, patients responded equally well to treatment with erlotinib regardless of whether their tumors had abnormally high levels of the EGFR protein.

Patients receiving erlotinib were more likely to have side effects such as diarrhea, infections, mouth ulcers, and a skin rash. In most cases, these side effects were not severe and did not reduce patients’ quality of life.

In the erlotinib group, patients who developed a skin rash tended to survive for longer than those who did not. A similar relationship between skin rash and survival has been observed in trials of erlotinib in other types of cancer, observed James Abruzzesse, M.D., of the University of Texas' M.D. Anderson Cancer Center in Houston, who commented on the study’s results at the ASCO presentation.

(Note: final results from the trial were subsequently published in the May 20, 2007, Journal of Clinical Oncology; see the journal abstract ⁵.)

Comments

Survival for patients in the gemcitabine-plus-placebo arm of this study was similar to that of patients treated with gemcitabine in other trials in advanced pancreatic cancer, said Abbruzzesse. This provides reassurance that the better outcomes seen for patients in the erlotinib arm are an effect of the added drug and not a result of poorer-than-expected outcomes among patients treated with gemcitabine and a placebo, he added.

However, it would be premature to conclude from this study that all patients with advanced pancreatic cancer should now be treated with erlotinib plus gemcitabine, Abbruzzesse concluded. More studies are needed to better identify the patients who are most likely to benefit from this combination drug regimen, he said.

Glossary Terms

A drug used to treat symptoms of cancer of the colon, breast, stomach, and pancreas. It is also used in a cream to treat certain skin conditions. 5-FU stops cells from making DNA and it may kill cancer cells. It is a type of antimetabolite. Also called 5-fluorouracil and fluorouracil.

The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also called epidermal growth factor receptor, ErbB1, and HER1.

A protein that speeds up chemical reactions in the body.

A drug used to treat certain types of non-small cell lung cancer. It is also used together with gemcitabine to treat pancreatic cancer and is being studied in the treatment of other types of cancer. Erlotinib is a type of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Also called CP-358,774, erlotinib hydrochloride, OSI-774, and Tarceva.

The active ingredient in a drug that is used to treat pancreatic cancer that is advanced or has spread. It is also used together with other drugs to treat breast cancer that has spread, advanced ovarian cancer, and non-small cell lung cancer that is advanced or has spread. It is also being studied in the treatment of other types of cancer. Gemcitabine blocks the cell from making DNA and may kill cancer cells. It is a type of antimetabolite

A statistics term. The middle value in a set of measurements.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treatments.