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When combining new oral anti-cancer agents with standard chemotherapy, timing may be crucial

(NEW ORLEANS) -- Timing may be everything when it comes to combining the new-generation oral, molecularly targeted anti-cancer agents with standard chemotherapy drugs, UC Davis Cancer Center researchers reported Saturday at the annual meeting of the American Society of Clinical Oncologists.

"Many of the new molecularly targeted anti-cancer agents work by inhibiting cancer cell division and growth -- but in doing so, the new agents could diminish the effectiveness of chemotherapy, which depends on rapid cell cycling," said senior investigator Paul Gumerlock, professor of hematology/oncology at UC Davis Cancer Center. "Because of this, it could be very important in what sequence the new agents are combined with standard chemotherapy drugs."

To test the notion, Gumerlock and his colleagues focused on a new oral epidermal growth factor receptor inhibitor known as erlotinib. Recently, several large clinical trials have compared standard chemotherapy alone to standard chemotherapy plus an oral EGFR inhibitor like erlotinib in the treatment of non-small cell lung cancer. Little if any benefit was found from the addition of an EGFR inhibitor in these trials, in which the EGFR inhibitor and chemotherapy were administered simultaneously.

The UC Davis Cancer Center team set out to determine whether sequential administration would make a difference. The researchers tested erlotinib alone, the standard chemotherapy agent docetaxel alone, the two drugs simultaneously, and the two drugs sequentially. All the tests were done in the laboratory using human non-small cell lung cancer cells.

"We predicted that giving docetaxel first, then erlotinib, would be more effective than giving the erlotinib first, giving both drugs simultaneously or giving either drug alone" Gumerlock said. "And that proved to be true."

Docetaxel, a standard first-line chemotherapy drug for non-small cell lung cancer, works in th
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