Nav: Home

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

June 05, 2004

(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 the same way other standard chemotherapy agents do: by killing rapidly dividing cells. The approach destroys cancer cells, which are characterized by out-of-control growth, but also some healthy growing cells, including cells in hair follicles.

Erlotinib, in contrast, works by blocking certain signals that cancer cells need in order to reach the cell-division stage, or mitosis.

Gumerlock theorizes that when erlotinib is given simultaneously or just before docetaxel, fewer cancer cells reach mitosis and become vulnerable to chemotherapy, thereby diminishing chemotherapy's effectiveness.

Clinical testing will be required to determine whether Gumerlock's laboratory findings hold true in patients. Based on his preclinical work, a phase I trial of docetaxel followed by erlotinib in patients with non-small cell lung cancer is already under way at UC Davis Cancer Center. Angela Davies, assistant professor of hematology/oncology at UC Davis Cancer Center, is principal investigator.

Gumerlock believes timing and sequencing may be crucial when combining chemotherapy with other molecularly targeted agents, not just erlotinib.

In a related presentation at the ASCO meeting, Gumerlock reported that in laboratory testing of tumors in mice, a selective proteasome inhibitor, PS-341, significantly inhibited non-small cell lung cancer growth when administered sequentially with docetaxel. But PS-341 had only a modest effect when delivered alone -- and no effect when delivered simultaneously with docetaxel.

"We've been delivering these drugs the same way we've delivered chemotherapy, assuming that the more we can give, and the longer we can give it, the better," Gumerlock said.

"But that may not be true. These molecularly targeted drugs are oral drugs, with such low toxicity and convenience that they can be given every day. But just because you can give a drug every day, it doesn't mean that is the best regimen. We hope to have some answers soon."
-end-
UC Davis Cancer Center is the only National Cancer Institute-designated cancer center between San Francisco and Portland, Ore., a region the size of Pennsylvania. It is ranked by U.S. News & World Report as one of the nation's top 50 cancer treatment centers.

University of California - Davis Health System

Related Chemotherapy Articles:

Chemotherapy drug may increase vulnerability to depression
A chemotherapy drug used to treat brain cancer may increase vulnerability to depression by stopping new brain cells from growing, according to a new King's College London study out today in Translational Psychiatry.
Sperm changes documented years after chemotherapy
A Washington State University researcher has documented epigenetic changes in the sperm of men who underwent chemotherapy in their teens.
Depressed patients are less responsive to chemotherapy
A brain-boosting protein plays an important role in how well people respond to chemotherapy, researchers report at the ESMO Asia 2016 Congress in Singapore.
Breast cancer study predicts better response to chemotherapy
It is known from previous research that the ER-beta estrogen receptor often has a protective effect.
Personalizing chemotherapy to treat pediatric leukemia
A team of UCLA bioengineers has demonstrated that its technology may go a long way toward overcoming the challenges of treatment for acute lymphoblastic leukemia, among the most common types of cancer in children, and has the potential to help doctors personalize drug doses.
How gut microbes help chemotherapy drugs
Two bacterial species that inhabit the human gut activate immune cells to boost the effectiveness of a commonly prescribed anticancer drug, researchers report Oct.
Molecule prevents effect of chemotherapy
For the last three years the research team has been working on the development of a so-called biomarker to predict treatment effectiveness.
Study provides new clues to leukemia resurgence after chemotherapy
For the first time, researchers have discovered that some leukemia cells harvest energy resources from normal cells during chemotherapy, helping the cancer cells not only to survive, but actually thrive, after treatment.
Dialing up chemotherapy for pancreatic cancer with ultrasound
Researchers at Haukeland University Hospital in Bergen, Norway have combined a laboratory ultrasound technique called 'sonoporation' with the commercially-available chemotherapy compound Gemcitabine to increase the porosity of pancreatic cells with microbubbles and to help get the drug into cancer cells where it is needed.
Vitamin A may help improve pancreatic cancer chemotherapy
The addition of high doses of a form of vitamin A could help make chemotherapy more successful in treating pancreatic cancer, according to an early study by Queen Mary University of London.

Related Chemotherapy Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...