Erlotinib Plus Gemcitabine Boosts One-Year Survival in Pancreatic CancerKey Words
Pancreatic cancer, erlotinib"> (Tarceva®),
targeted therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
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.)
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.
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