Making Chemo More Tolerable

Making Chemo More Tolerable

 

Researchers and physicians are trying new ways to ease the notorious side effects of chemotherapy and make it more tolerable.

While many of the new cancer drugs hitting the market in recent years have markedly improved care, they haven’t yet displaced chemo, the workhorse of oncology.

Researchers are trying tactics including reformulated versions of chemo drugs and still-experimental technology like a tiny implantable sponge that soaks up excess chemo, after it hits the tumor but before it can enter the rest of the bloodstream.

Longer-standing tactics such as spacing out chemotherapy infusions, giving lower doses or treating side effects are also making the treatments less toxic for some patients, doctors say.

Dr. Ezra Cohen, professor of medicine, associate director for translational science and co-leader, solid tumor therapeutics program, at UC San Diego Moores Cancer Center.
Dr. Ezra Cohen, professor of medicine, associate director for translational science and co-leader, solid tumor therapeutics program, at UC San Diego Moores Cancer Center. PHOTO:NICK ABADILLA/UC SAN DIEGO

Traditional chemotherapies remain valuable in treating many cancers that can’t be attacked with newer drugs. They also are used in combination with new treatments to hit cancer from different angles. Many patients with breast cancer, leukemia, colon cancer and others still receive chemo, with side effects including hair loss and nausea.

Although many types of drugs could be described as chemotherapy—the word simply means chemical therapy—the term is usually reserved for older classes of cancer medications that work by killing fast-growing cells in the body. These include not just cancerous cells, which divide and grow uncontrollably, but also some healthy cells, such as those in hair follicles and the gut.

 Newer drugs are more targeted in their attack, homing in on tumors more precisely and sparing healthy cells. Some of these drugs target a genetic flaw in a tumor, while others, called immunotherapies, harness the body’s immune system to attack cancerous cells. But the drugs don’t work in all cancers.

“There have been major advances in targeted therapy and immunotherapy,” said Ezra Cohen, a medical professor and hematologist at UC San Diego Moores Cancer Center. “We’re not there for everybody yet, so chemo is still going to have an important role in the treatment of cancer certainly in our generation,” Dr. Cohen said.

One experimental approach to improving chemotherapy is to use a sponge-like material to soak up excess drug after it hits a tumor. The technology, developed by the California startup ChemoFilter Inc. and the Department of Energy’s Lawrence Berkeley National Laboratory, is designed for use alongside chemotherapy delivered directly to the site of a tumor via a catheter.

Chelsea Chen at NCEM\'s Tecnai microscope with polymer material that will improve liver cancer treatment.
Chelsea Chen at NCEM\’s Tecnai microscope with polymer material that will improve liver cancer treatment. PHOTO: ROY KALTSCHMIDT/BERKELEY LAB

The chemotherapy feeds through an artery into the organ affected by cancer; the sponge-like device is placed in a vein that drains the organ. The device is coated with a chemically active resin that attracts and traps the chemotherapy, “before it spreads out to the rest of the body,” says Steven Hetts, a radiologist at University of California, San Francisco School of Medicine, who helped design the technology and found ChemoFilter. The device has been tested in pigs but not humans. The aim is to start human trials within the next few years, Dr. Hetts said.

Other companies are redesigning traditional chemos to make them easier to take. Swedish drug maker Oasmia Pharmaceutical AB is attempting to develop water-soluble versions of long-standing chemotherapies including docetaxel. Because the older drugs don’t dissolve easily in water, other additives are used to dissolve them so they can be infused into the bloodstream. These additives can heighten side effects, according to the National Cancer Institute.

Oasmia’s approach is to coat the drugs with nanoparticles that make them water soluble, with the aim of lowering side effects and reducing the time an infusion takes. The company is following the lead of Celgene Corp., which sells Abraxane, an improved formulation of the chemotherapy paclitaxel.

Doctors say they have also made strides in understanding the best ways to deliver existing chemotherapies.

One way is to use multiple chemotherapies at lower doses, says Otis Brawley, chief medical officer of the American Cancer Society. Because each chemo will have somewhat different side effects, “you spread the side effects out a bit” while attacking the cancer in multiple ways, he said.

Anne Tsao, a thoracic oncologist at University of Texas MD Anderson Cancer Center in Houston, says physicians sometimes space out doses to give people time to recover. The drug pemetrexed, for instance, is intended to be given once every three weeks. “If a patient has a difficult recovery we might give it every four weeks,” without much difference in efficacy, she said.

Medications to ease chemotherapy’s side effects, such as nausea and reduced white blood-cell counts, also are improving patient care.

John Greenbush, a 72-year-old undergoing treatment in San Diego for squamous cell carcinoma of the neck, says he endured a recent round of the chemotherapy cisplatin, received alongside radiation, with the help of several antinausea medications.

At first his physician, Dr. Cohen of UCSD, gave him Compazine and Zofran, which worked “pretty well” for a while, Mr. Greenbush says. When the nausea got worse again, he started taking a third drug, Emend, which worked better, allowing him to eat a liquid diet, he says.

Overall, that round of chemo was still “nasty stuff,” Mr. Greenbush says, despite the anti-nausea meds. “I lost my hair and all that stuff. It was not a whole lot of fun.”

Dr. Cohen calls cisplatin plus radiation a “difficult regimen to tolerate,” but one he employs when there is a chance to eradicate a patient’s cancer.

With some other chemotherapy treatments these days, he says, the “reputation is worse than the reality.”

“Yes, chemotherapy still has side effects. But it’s certainly becoming less of a problem,” Dr. Cohen says.

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