美国国家公共电台 NPR Old-Style Chemo Is Still A Mainstay In The Age Of Targeted Cancer Therapy（在线收听）

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.