Old-Style Chemo Is Still A Mainstay In The Age Of Targeted Cancer Therapy

Mar 13, 2017
Originally published on March 14, 2017 8:35 am

Chemotherapy remains one of the mainstays of cancer treatment, but these harsh drugs are slowly being edged aside in medical research, as new treatments, like immunotherapy, grab the spotlight.

Still, this is not the end of the road for chemotherapy. For one thing, doctors are coming to realize that some of these drugs are useful for more than just killing cancer cells.

Dr. Robert Comis, a professor and oncologist at Drexel University, had the first inkling of this phenomenon 30 years ago, after he ran a test involving radiation therapy along with just two cycles of chemotherapy — far too few cycles to be truly effective. Even so, the patients did much better than he'd expected.

"The only explanation was there was this large effect that involved the whole body," says Comis, who also co-leads the ECOG-ACRIN Cancer Research Group in Philadelphia. Chemotherapy wasn't simply killing cancer cells, he realized; apparently it was stimulating the immune system, too.

And that meant these old-fashioned drugs could play a new role.

To be sure, chemotherapy is still used a lot for its ability to kill cancer cells, even in clinical trials that involve newer treatments like immunotherapy.

Sometimes, fast-acting chemotherapy can help slow an aggressive cancer, for instance, and give the slower-acting immunotherapy treatments a chance to work. Chemo is also sometimes paired with still-unproven treatments to improve their odds of success.

That was the case for 69-year-old Deborah Mazia, who ended up at the Johns Hopkins Bloomberg-Kimmel Institute in Baltimore after being diagnosed with breast cancer around Thanksgiving of last year.

The news was bad. Mazia's doctor told her that she had triple-negative breast cancer, a malignancy that tends to respond poorly to conventional treatment.

"So, [the doctor] held my hand," Mazia recalls, "and she says, 'Listen. It's Stage 4. And if you want to do anything, do it now.' "

Mazia didn't hesitate. She enrolled in a study that combines a potent chemotherapy drug with either an immunotherapy agent or a placebo. She still doesn't know whether she's getting the experimental treatment or not.

"But I don't care," she says. "I'm excited, because this is where I think things are going research-wise, so I'm thrilled."

Immunotherapy sometimes produces dramatic results, but most of the time it doesn't work. So for a clinical trial like this, it makes sense to give standard chemotherapy along with the experimental treatment.

Dr. Leisha Emens, the oncologist running the study at Hopkins, says this is just one way she continues to use chemotherapy in clinical trials. She and her colleagues are also exploring an underappreciated role of chemotherapy — its ability to directly affect the immune system.

"In fact, it can either help or hurt the immune response to cancer," Emens says. She's interested in the helpful part, of course. For instance, certain chemotherapy drugs can kill a type of T-cell that makes cancers more resistant to treatment.

It also appears that after chemotherapy kills cancer cells, the debris that's left can sometimes stimulate an immune reaction. That leftover material is like a vaccine, in that it trains the immune system to recognize and attack remaining cancer cells.

And in some cases, Emens says, doctors can use lower doses of these highly toxic and often unpleasant drugs to harness the immune system. That interplay is an active area of research, she says.

The National Cancer Institute is focusing research dollars on that very issue, as it phases out traditional studies that involve only chemotherapy drugs. For decades, the institute has been funding research to find new combinations and doses, and made incremental improvements in cancer treatments. But those studies are disappearing.

Dr. Elad Sharon at the NCI says there's been a natural shift, instead, toward the next frontier of cancer treatment — so-called targeted therapies. Unlike chemotherapy, these targeted drugs don't blindly kill fast-growing cells, but instead home in on specific vulnerabilities within malignant cells. Immunotherapy is one type of targeted therapy.

"That's something that has really captured the imagination of the field," Sharon says. As time goes on, he says, "definitely we're seeing more and more of these targeted agents become the standard that people expect to receive."

But this is hardly the end of the road for traditional chemo.

"I think there are some diseases where chemotherapy has really been very effective, and has led to significant cures," Sharon says. It's "probably going to be very hard for any targeted agents to beat them."

Comis agrees. "We're in a transition state right now where the types of available treatments are changing," he says. "But we can't lose sight of the fact that cytotoxic chemotherapy has cured many, many patients."

And there are still ways to make these old standby drugs more effective, Comis says, sometimes by using them in combination.

"We just completed a study which showed that, in metastatic prostate cancer, the addition of a chemotherapy drug, God forbid, increased survival by 18 months in the highest risk groups," he says. "Eighteen months!"

That's much better than the improvements reported for most targeted treatments. In an ideal world, highly toxic chemo would give way altogether to gentler and more effective medicines for patients like Deborah Mazia. But Comis, for one, doesn't see that day coming anytime soon.

You can contact Richard Harris at rharris@npr.org.

Copyright 2017 NPR. To see more, visit http://www.npr.org/.

DAVID GREENE, HOST:

Today in Your Health, we're taking a close look at chemotherapy. It's been a mainstay of cancer treatment for decades, but that method is slowly being edged aside in medical research as new treatments, like immunotherapy, grab the spotlight.

This is not the end of the road for chemotherapy, though. For one thing, doctors are coming to realize that some of these drugs are useful for more than just killing cancer cells. NPR's Richard Harris has the story.

RICHARD HARRIS, BYLINE: For Dr. Robert Comis, the first inkling that chemotherapy drugs did more than simply kill cancer cells came during a study 30 years ago. It combined chemo with radiation therapy, and some patients did surprisingly well even though they had nothing like a full course of chemotherapy.

ROBERT COMIS: Well, how could these two cycles of chemotherapy mean anything? And the only explanation was that there was this large effect that it involved the whole body.

HARRIS: Comis, at the ECOG-ACRIN Cancer Research Group in Philadelphia, realized that chemotherapy wasn't simply killing cancer cells. It was apparently stimulating the patients' immune systems.

COMIS: And lo and behold now, 30 years later, that's probably the explanation for what we saw then.

HARRIS: Chemotherapy is still used a lot for its ability to kill cancer cells, even in clinical trials that involve next-generation treatments like immunotherapy. Sometimes, fast-acting chemotherapy can help slow an aggressive cancer and give the slower-acting immunotherapy treatments a chance. For instance, researchers at Johns Hopkins are testing out new immunotherapy agents paired with traditional chemotherapy.

DEVON ISAAC: So how have you been since last treatment?

DEBORAH MAZIA: Fine, except - you know, I had the cold. I don't anymore.

ISAAC: OK, good.

MAZIA: I was pretty exhausted.

ISAAC: OK.

HARRIS: Deborah Mazia has volunteered for a study of the Hopkins hospital in Baltimore.

ISAAC: All right. Your vital signs look good. Your heart rate's a little high, but I'm guessing that's because we're on the radio.

(LAUGHTER)

HARRIS: After nurse Devon Isaac leaves to check on the status of Mazia's infusion, the 69-year-old Maryland woman tells her story. Around Thanksgiving, she noticed a lump in her breast and swelling under her arm.

MAZIA: So my daughter said - 'cause I thought maybe it's nothing. There's no cancer in my family, no nothing. So she said, I think you should get it checked out.

HARRIS: The news was bad. Her doctor told Mazia that she had triple-negative breast cancer. That's a cancer that responds poorly to conventional treatment.

MAZIA: So she held my hand. And she goes listen, it's stage 4. And if you want to do anything, do it now.

HARRIS: So Mazia ended up here in a trial that combines a potent chemotherapy drug with either an immunotherapy agent or a placebo.

MAZIA: And it's a double-blind study, which means I don't know if I'm getting the immunotherapy or I'm getting a placebo.

HARRIS: How does that feel, sort of being part of an experiment where you're not even sure what you're getting?

MAZIA: I don't care. I'm excited 'cause I think that this is, like, where things are going researchwise. So I'm thrilled.

HARRIS: Immunotherapy sometimes produces dramatic results. But most of the time, it doesn't work at all. So for a clinical trial like this, it makes sense to give standard chemotherapy along with the experimental treatment.

Dr. Leisha Emens, who's running this study, says she and her colleagues are also exploring the underappreciated role of chemotherapy agents - and that is their ability to affect the immune system.

LEISHA EMENS: And in fact, it can either help or hurt the immune response to cancer.

HARRIS: She's interested in the helpful part, of course. Certain chemotherapy drugs can kill T-cells. These immune system cells can make cancers more resistant to treatment. It also appears that after chemotherapy kills cancer cells, the debris that's left over can sometimes stimulate an immune reaction that targets the remaining cancer cells.

EMENS: Where you sort of get a vaccine-like effect.

HARRIS: And Emens says, in some cases, doctors can use lower doses of these highly toxic and often unpleasant drugs.

EMENS: These lower doses of chemotherapy are not designed to treat the cancer directly the way you typically think of chemotherapy. But they're designed specifically to harness the immune system.

HARRIS: The interplay of immunity and chemotherapy is an active area of research with effects dependent on the specific drugs and dosages.

EMENS: So we really need to learn more about all of these different types of standard cancer drugs and how they interact with the immune system in order to harness their ability to synergize with immunotherapies most effectively.

HARRIS: The National Cancer Institute is focusing research dollars on that question. They're also phasing out traditional studies that involve only chemotherapy drugs. For decades, they'd been funding research to find new combinations and doses and have made incremental improvements in cancer treatments.

Dr. Elad Sharon at the cancer institute says there's a natural shift toward the next frontier of cancer treatments, so-called targeted therapies. Unlike chemotherapies, these drugs don't blindly kill fast-growing cells. They home in on specific vulnerabilities within cancer cells. Immunotherapy is one type of targeted therapy.

ELAD SHARON: That's something that has really captured the imagination of the field. And so most new clinical trials or experimental regimens seem to be either looking at that or some other form of targeted therapy.

HARRIS: So are we looking at the end of the road for chemotherapy? Not so fast, Sharon says.

SHARON: I think there are some diseases where chemotherapy has really been very effective and has led to significant cures that are probably going to be very hard for any targeted agents to beat them. But as time goes on, definitely. I mean, I think we are seeing more and more of these targeted agents actually become the standard that people expect to receive.

COMIS: We're in a transition state right now where the types of available treatments are changing.

HARRIS: Again, Robert Comis.

COMIS: But we can't lose sight of the fact that cytotoxic chemotherapy has cured many, many patients.

HARRIS: And Comis says there are still ways to make these old standby drugs more effective.

COMIS: We just completed a study which showed that in metastatic prostate cancer, the addition of a chemotherapy drug, God forbid, increased survival by 18 months in the highest-risk groups - 18 months.

HARRIS: That's much better than the improvements reported for most targeted agents. In an ideal world, highly toxic chemotherapy drugs would give way altogether to gentler and more effective treatments for patients like Deborah Mazia. But Comis, for one, doesn't see that day coming anytime soon. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.