The worst part of Colleen Combes’ breast cancer treatment three years ago, besides losing her hair, was the awful mouth sores caused by chemotherapy.
These ulcers “were like canker sores that had broken open, only much worse. They were everywhere – on my tongue, the inside of my lips, my cheeks. It was very painful. I couldn’t eat. It was difficult to talk,” says Combes, a 41-year old Rockland woman currently on leave from her job in a law firm.But in January, when Combes’ cancer had spread and she needed a stem cell transplant (a major procedure akin to a bone marrow transplant), things were different. She had no mouth sores despite the even higher doses required in the second round of chemotherapy.
Just before the transplant, Combes agreed to participate in a test of a new drug to prevent mouth sores. She still doesn’t know for sure whether she got the drug or a placebo, but she had “no mouth sores, nothing. I was ecstatic.” Perhaps because of this, she says, she also went home sooner than most patients.
Until recently, the main reason doctors had to limit or stop chemotherapy in many patients was damage to the bone marrow or immune system – the body’s infection-fighting equipment.
Now, that problem has become more manageable, thanks to drugs that protect the marrow, and mouth sores and other oral complications are becoming the number-one treatment-limiting issue, says Dr. Stephen Sonis, chief of oral medicine, oral maxillofacial surgery and dentistry at Brigham and Women’s Hospital in Boston.
“It’s a major, major problem,” agrees Dr. Jerome Groopman, chief of experimental medicine at Beth Israel Deaconess Medical Center.
This year alone, 1.2 million new cases of cancer will be diagnosed among Americans. About 400,000 patients will develop oral complications from their treatment, many to the point where they’ll need morphine or will have to stop treatment altogether, which can affect survival.
Those like Combes who have stem cell or bone marrow transplants, which involve high-dose chemotherapy, are at special risk: 75 to 80 percent get severe oral complications, says Dr. Philip Fox, former clinical director of the National Institute of Dental and Craniofacial Research at NIH and now research and development director at Amarillo Biosciences Inc. in Amarillo, Tex.
Indeed, oral complications from cancer treatment are emerging as such a major problem that the National Institutes of Health recently launched a public education campaign to raise consciousness of the issue among patients, doctors and dentists.
Like cancer cells, cells that constitute the mucosal lining of the mouth have a quick turnover rate. This means that, like cancer cells, they are easily killed by chemotherapeutic agents.
As cells in the mouth die, they release molecules called cytokines, which cause inflammation that further damages mouth tissue. The resulting breaks and ulcers then make it easy for germs from the mouth to enter the bloodstream and cause systemic infection, particularly since the immune defenses are also hurt by chemotherapy.
In other words, once the lining of the mouth is damaged, patients lose a key “physical barrier” to infection, says Groopman. On top of that, patients often have so much pain from mouth sores that they can’t eat or absorb much-needed nutrients.
With head and neck cancers, which will be diagnosed in about 30,000 Americans this year, the main problem is the radiation that patients get after surgery. Radiation can destroy saliva glands, as well as blood vessels and bones in the mouth and jaw.
Saliva is essential, not just because it lubricates the mouth but because it contains proteins that fight viruses, yeast and bacteria. Without saliva, patients have difficulty swallowing, chewing, speaking and fighting infection, which means tooth decay can become rampant.
In addition, radiation can damage blood vessels and the jawbone to such a degree that if a person later needs a tooth extracted, the bone may never heal. Taken together, this means that patients with head and neck cancer should get major dental work done before radiation.
But it’s chemotherapy, because it affects more people, that’s an even larger concern, specialists say, and some drugs, especially fluorouracil (5-FU), cytarabine, methotrexate, and some combinations of drugs, are particularly damaging.
On the plus side, scientists have “learned more about mucositis, or mouth sores, in the last two years than in the prior 50,” notes Sonis. As a result, a number of new drugs to prevent or treat mucositis are now in testing.
At the University of Connecticut Health Center in Farmington, Dr. Douglas Peterson, head of oral diagnosis, has completed a study in stem cell transplant patients of a drug called misoprostol, already on the market for stomach ulcers. Taken in mouthwash form within two hours of the start of chemotherapy, he says, the drug may reduce oral tissue injury. Other data, however, suggests that in tablet form, the drug can make mucositis worse.
At the Fred Hutchinson Cancer Research Center in Seattle, Dr. Mark Schubert, director of oral medicine, along with Sonis and others, is testing a new antimicrobial drug, IB367. The idea, says Schubert, is to see if by killing oral bacteria and yeast, the drug can reduce the severity of mucositis. This is the drug Colleen Combes, the breast cancer patient, thinks she had.
Elsewhere, researchers are testing growth factors called KGF-1 and KGF-2, designed to stimulate oral mucosal cells called keratinocytes. Others are testing TGF-beta3, a drug that stops cells from dividing and hence might help cells in the mouth escape the damage from chemotherapy drugs.
Still others are testing an amino acid called glutamine that, when swished in the mouth, might help mucosal tissue to regrow. Also under study is benzydamine, a drug that may block inflammation of mouth tissue, and Il-11, a drug that may block mucositis in multiple ways.
For patients like Combes, these and other drugs in the works hold the promise not only of increasing quality of life during and after cancer treatment but, because they may enable more people to complete treatment, may boost the chances of survival.
It’s not easy to get yourself to the dentist when you’ve just been told you have a life-threatening disease. “People with cancer have a gazillion things to think about,” says Sonis of the Brigham. “It’s like sitting under a dump truck and getting unloaded on. But to the extent that they can be proactive and get to the dentist, it’s a huge help.”
Treat the mouth before therapy
If you’re facing chemotherapy for any kind of cancer or radiation for head and neck cancer, it’s important to get major dental work done before you start treatment, according to the National Institutes of Health.
With radiation in particular, treatment can damage oral tissues so severely that dental work later, including tooth extractions and gum surgery, may be difficult or impossible.
During cancer treatment, mouth care is also crucial, which means you should:
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Brush teeth gently with an extra-soft toothbrush or foam sponges. Brush after every meal and at bedtime.
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Floss once a day to remove plaque, unless your oncologist says your blood platelet levels are so low that the risk of bleeding is too great.
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Rinse your mouth often with water or salt water and ask your oncologist or dentist if you should use a fluoride gel or rinse as well.
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Don’t use mouthwashes that contain alcohol, as most commercial mouthwashes do.
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Use a saliva substitute such as Biotene to help keep your mouth moist.
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Eat soft, easy-to-chew foods.
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Don’t eat spicy, sour or crunchy foods.
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Eat foods that are warm but not too hot or cold.
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Avoid alcoholic drinks.
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If you smoke or chew tobacco, quit and ask your oncology team for help if you need it.