The evolution of chemo: From a brutal beginning to a tolerable today
When Stacey Hanks was diagnosed with breast cancer, her doctor recommended the standard treatment — surgery to cut out the tumor, followed by chemotherapy and radiation
“I was on board for everything but the chemo,” Hanks says. “My cousin went through chemo 15 years ago, and it was rough.”
After a heart-to-heart talk with her family, Hanks finally said yes to her doctor’s plan.
“I wanted the cancer gone, and to raise the odds that it would never come back,” she says.
“Chemotherapy gave me added assurance.”
To her surprise, the treatment was much easier than she anticipated.
“Other than losing my hair and feeling exhausted for a few days after each session, I had virtually no side effects, says the 50-year-old Hanks.
Today, her previously long hair has grown back thicker than before, and she’s wearing it in a short new “do.”
“I can feel the ocean breeze on my neck. It’s nice,” says Hanks, who raises quarter horses in the coastal town of Rockport, Texas.
For most people, the word “chemotherapy” calls to mind crippling nausea, debilitating fatigue and hair loss.
That’s understandable, says Michael Keating, M.D., professor of Leukemia.
“A lot of people have inflated fears about how bad chemo is going to be,” he says. “They’ve heard horror stories from friends or relatives who’ve had it in the past. We’ve come a long way — the treatment is much easier to tolerate today. But people still remember yesterday’s chemo when the drugs could be as brutal on the patient as they were on the tumor.”
Keating, who’s been a cancer doctor for more than 40 years, has some vivid memories of his own.
“In the 1970s and ’80s, patients waited outside MD Anderson to be picked up and driven home after chemotherapy. They held turquoise-colored, kidney-shaped basins because their nausea was so bad. Some required sedation. It was that distressing.”
Those days are gone, but Keating says some people are frightened enough to actually decline chemo, even when he tells them doing so decreases their chances of a cure.
“I assure them that we have tricks today — like anti-nausea medications, alternative therapies such as acupuncture, meditation and yoga, and new ways of delivering chemo drugs — that make them much easier to tolerate.”
How chemo works
When a normal cell becomes worn out or damaged, it divides to create a copy of itself.
The old cell dies, and the new one takes its place.
“At this very second, cells in your body are replacing themselves in an orderly and organized way,” says William Plunkett Jr., Ph.D., professor of Experimental Therapeutics.
But when a normal cell mutates and becomes cancerous, its division and growth spin out of control.
“Most cancer cells replicate rapidly and often,” Plunkett explains. “More and more of them are produced until they form a tumor that intrudes upon and starves normal tissues.”
To win this “battle of the cells,” doctors prescribe chemotherapy, with “chemo” meaning chemicals, and “therapy” meaning “treatment” — the use of chemicals to treat cancer.
Some chemo drugs kill cancer cells outright. Others keep cancer cells from dividing and reproducing. But chemo drugs can’t distinguish between healthy cells and cancer cells, so they attack both.
“Healthy cells become ‘collateral damage’ in the fight to destroy cancerous ones,” Plunkett says. “That’s why patients become sick and have side effects like vomiting, diarrhea, fatigue, hair loss, mouth ulcers, nerve damage and more. The drugs disrupt normal cells in virtually every area of the body.
“Each time chemo is given,” Plunkett says, “doctors must strike a balance between killing cancer cells and sparing normal cells.”
An accidental discovery
Chemotherapy owes its unlikely origin to a World War II naval tragedy.
On the night of Dec. 2, 1943, Germany launched a devastating air attack on the Italian port of Bari, sinking or damaging 40 ships. One of these, the U.S. ship SS John Harvey, was carrying a secret cargo of mustard gas shells that exploded on impact. Military personnel forced to swim through the resulting toxic mess ended up with severe and fatal burns.
Autopsies revealed that the mustard gas killed the soldiers’ rapidly dividing white blood cells, prompting doctors to wonder if it could do the same for cancer cells, which also divide and grow quickly.
The military hired pharmacologists to study the use of mustard gas chemicals, and from these trials the first chemotherapy drug, mechlorethamine, was created to treat lymphoma.
Patients showed a remarkable improvement and more drugs followed.
Today, more than 100 chemotherapy medications are available to tame most tumors.
Most are far easier to take than the chemo drugs of yesteryear. Advances in anti-nausea medicines, along with new ways of delivering chemo drugs — such as encasing them in fat bubbles to cushion absorption, or latching them onto proteins that seek out tumors and avoid healthy cells — are helping patients undergo chemo with fewer side effects.
“You may not feel great all the time,” says Laura Michaud, Pharm. D., manager of Clinical Pharmacy Services. “But you can keep going. And that’s a big improvement on what chemo used to be like.”
A big breakthrough, Michaud says, came in the early 1990s when a new class of drugs called serotonin antagonists were introduced. These medications, whose trade names include Zofran, Aloxi, Kytril and others, block stimulation of the nausea receptors in the brain.
“Before serotonin antagonists came along, the drugs we had to control nausea just weren’t that effective,” Michaud says. “Some people had to be hospitalized during chemotherapy — the nausea and vomiting were that bad. The only way to get patients through it was to sedate them.”
Today, most chemo is given in outpatient clinics, and patients are home in time for dinner.
“People getting chemo are living full lives,” Michaud says. “Many can still hold down jobs and care for their families.”
Jim Nudo’s story
Jim Nudo stayed “on the job” throughout his one-year course of chemo for lung cancer.
“I assumed I’d need to take a leave of absence, but it wasn’t as bad as I imagined,” says Nudo, whose company makes safety shut-down systems for refineries and chemical production facilities.
He needed anti-nausea medicine only once, when a tainted meal from a restaurant — not chemo — made him sick.
That’s a stark contrast to what Nudo’s father experienced 15 years ago when he, too, battled lung cancer.
“My dad had a much harder time,” says Nudo, who developed the disease despite having never been a smoker. “My treatment wasn’t a walk in the park, either — I’d sometimes get fatigued and lose my appetite — but my experience was far less grueling than my dad’s.”
Chemo helped slow down Nudo’s cancer, but his disease was advanced when detected and has spread beyond his lungs.
Now he’s on to the next phase of treatment, and is trying a new-generation immunotherapy drug. Rather than attacking the cancer directly, as chemo does, immunotherapy rallies a patient’s own immune system to fight the disease. The immune cells seek out and destroy cancer in the same way they destroy bacteria, viruses and other invaders. Immunotherapy drugs are a recent breakthrough in the war against cancer, and are credited with curing former President Jimmy Carter’s metastatic melanoma.
But the drugs don’t work for everybody, and researchers are working to understand why. (See "Removing cancer’s unpredictable advantage") When they do work, as they did for President Carter, the results have been particularly impressive.
“Immunotherapies are pretty well tolerated,” Michaud says. “Unlike chemo, they don’t contain toxins that poison cells, so there’s no hair loss or blood cell abnormalities. But they have a different set of potential side effects.”
The surging immune response brought on by this new generation of drugs can overshoot its target and attack healthy tissues and organs, similar to an autoimmune disorder.
“Fortunately, the vast majority of such reactions are not severe and can be reversed when the medication is stopped,” Michaud says.
So far, Nudo has had no problems with the therapy.
“I’m feeling great,” he marvels. “It’s as though I’m on zero medications.”
He’s back to enjoying his favorite hobby, saltwater and freshwater fishing, and is helping his daughter and son remodel their condominiums.
“Life is wonderful,” he says.
A practical partnership
Immunotherapy is an extremely important new weapon in the cancer doctor’s arsenal, but it doesn’t replace chemotherapy, Keating says.
He envisions the two working synergistically to cure more cancers.
“Chemo can wipe out a tumor, but if you have just one cell left, the tumor can come back. Today, we can use chemo to shrink the tumor, and then follow up with the immune drug. Pairing both therapies could make each more effective.”
Whether used alone or in combination with next-generation treatments, Keating says one thing is certain: “Chemotherapy will remain a mainstay of cancer therapy for the foreseeable future.”