Putting the Screws to Resistant Tumors

Cancers driven by EGFR responds to lapatinib with cetuximab

(RxWiki News) Cancer is one masterful disease process. Why? It's a master at finding its way around obstacles like treatment drugs. That's why it may take a combination approach to put the screws to some cancers.

Researchers have found in phase I study (tests drug safety) that combining Erbitux (cetuximab) and Tykerb (lapatinib) seems to work in cancers that no longer respond to therapies.

"Ask your oncologist if drug combinations are available."

Findings from a small clinical trial conducted at Georgetown Lombardi Comprehensive Cancer Center were presented at the American Society of Clinical Oncology annual meeting in Chicago, June 1-5, 2012.

The two drugs have been approved by the U.S. Food & Drug Administration to treat different types of cancer. Cetuximab treats advanced colorectal cancer and head and neck cancers, and lapatinib is approved for some types of breast cancer.

These drugs back up one another. Cetuximab blocks what's known as the epidermal growth factor receptor (EGFR) that's active in colon, head and neck and lung cancers.

The medication stops EGFR communication inside the cell. This means the cell doesn't get word it's supposed to grow and dies as a result.

Because cancer finds ways around these roadblocks, cells can become resistant to cetuximab when another receptor HER2 (ErbB2) enters the picture.

When lapatinib is added to the therapy, the HER2 and EGFR signals are both blocked, causing the cancer cells to die.

John Deeken, MD, a medical oncologist at Georgetown Lombardi Comprehensive Cancer Center, says, "By combining different targeted therapies, we hope to be able to overcome such resistance and turn off the cancer cell signal to grow."

Dr. Deeken, who is an expert in how cells process drugs, designed the trial involving 16 patients who had tumors that are driven by EGFR.

Participants received the standard dose of cetuximab intravenously once a week. The lapatinib was given in increasing dosages by mouth.

Common side effects of the combo therapy were diarrhea and rash, which were easily managed.

"While this study isn't designed to evaluate whether or not this combination of drugs works, we have seen some positive signs of clinical activity," Dr. Deeken said.

Of the nine patients who completed at least two treatment cycles, two had a partial response when their tumors shrunk by more than 30 percent. Two had stable disease during the treatment cycles or longer.

Dr. Deekan says that phase II studies are being developed to test this combination in individuals with colon as well as head and neck cancer.

GlaxoSmithKline, the maker of lapatinib, provided the drug for the study and supported the research.

All research is considered preliminary before it appears in a peer-reviewed journal.

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Review Date: 
May 29, 2012