IE 11 is not supported. For an optimal experience visit our site on another browser.

‘Smart-bomb’ drugs for lymphoma underused

Only a fraction of patients with hard-to-treat lymphoma ever try two breakthrough “smart-bomb” drugs that bring radiation straight to cancerous cells — with just two shots a week apart, not the usual months of care.
/ Source: The Associated Press

Only a fraction of patients with hard-to-treat lymphoma ever try two breakthrough “smart-bomb” drugs that bring radiation straight to cancerous cells — with just two shots a week apart, not the usual months of care.

The marketing failure has a manufacturer trying to sell off one of the drugs, and increasingly frustrated specialists worry it will jeopardize attempts to expand this promising new field to fight other cancers, too.

It’s called radioimmunotherapy, harnessing homing device-like immune cells — antibodies — with a radioactive drug. The antibodies zero in on cancer and drop their payload, without as much damage to surrounding healthy tissue as chemotherapy can cause.

Only two such drugs are sold today, the lymphoma fighters Zevalin and Bexxar. But more than half a dozen early stage studies of others — against some particularly deadly malignancies, including pancreatic cancer, brain cancers, and advanced prostate cancer — are under way.

The issue: Despite research showing they work well, fewer than 10 percent of lymphoma patients who are candidates for Zevalin and Bexxar ever use them, says Dr. Mark Kaminski of the University of Michigan, a hematologist who co-invented Bexxar.

Why? Specialists cite a complex list of reasons, including that most oncologists aren’t licensed to administer the radioactive infusion and must send their patients to a nuclear-medicine doctor. There’s also confusion about the risks of radiation, which studies suggest are minimal, and when the drugs work best — early, not as a last-ditch therapy.

“There’s lots of reasons to use them, and seems to be an inertia against them,” says Dr. Mitchell Smith, lymphoma chief at Fox Chase Cancer Center in Philadelphia. “I do see it as unfortunate.”

‘They hit a home run’
Indeed, sales are so weak that Zevalin maker Biogen Idec announced in December it was hunting a buyer to take over the drug. While the company insists Zevalin won’t come off the market, the move is prompting fear on cancer blogs and from patients considering radioimmunotherapy that the option may disappear.

“Basically, they hit a home run” scientifically, says Kaminski. “The shock wave that goes through here is that if you can’t get this to work in the marketplace, what’s the sense of developing anything else along this line?”

Kaminski laments that about once a month, a patient seeks him after other doctors discouraged the therapy or advised it only after exhausting other options, including a rigorous bone marrow transplant.

Adds Dr. Bruce Cheson, hematology chief at Georgetown University Hospital: “When patients are presented this option, they say it’s too good to be true: ’It’s only a week, and I have a 70 percent chance of responding to it.”’

At issue are so-called low-grade forms of non-Hodgkin’s lymphoma that strike thousands of Americans each year. They’re incurable, but patients typically live a long time, beating back increasingly hard-to-treat recurrences every few years.

The leading treatment is Genentech and Biogen Idec’s blockbuster seller Rituxan, a stand-alone antibody — no drug attached — that by itself kills cancer cells, and often is used together with chemotherapy to prolong a first remission. Rituxan is considered to have revolutionized lymphoma care.

But patients will relapse. When that happens, Zevalin and Bexxar are government-approved options. They use the same antibody target but with different radioactive drugs attached to give lymphoma a one-two punch. Studies suggest they fight the cancer’s return at least as well as months of standard chemo.

Longer remissions
More intriguing, about 20 percent of those patients have extremely long remissions, five to eight years. That’s more likely when the drugs are used for a first relapse, not later when repeated chemo has ravaged the immune system, says Fox Chase’s Smith.

Also, there’s mounting evidence from small studies that even more patients have long-term remission if they use radioimmunotherapy first, instead of waiting to relapse. A closely watched government trial is trying to prove that, by comparing Bexxar plus standard chemotherapy to Rituxan plus chemo in about 500 newly diagnosed patients. Results are due in two years.

If that study pans out, “it’ll have a huge impact on practice,” predicted Dr. James Armitage of the University of Nebraska Medical Center, who tries to calm worried patients that the option won’t disappear before that question is settled.

With radioimmunotherapy at a crossroads awaiting that science, proponents are talking up the drugs, to medical journals and patient advocacy groups. A petition pending before the Nuclear Regulatory Commission seeks to allow more oncologists to administer the shots. And Biogen Idec spokeswoman Naomi Aoki says her company is working to get more community oncologists licensed to use the drug, and plans to sell it to a company “also committed to making sure it’s available.”