Through clinical studies using long-term randomized, controlled trials, they explored how to prevent heart damage in childhood cancer patients treated with doxorubicin - a commonly used chemotherapy also known as Adriamycin.
The work was done at the University of Miami Department of Pediatrics’ Batchelor Children’s Research Institute and the Sylvester Comprehensive Cancer Center.
The studies were designed to discover if dexrazoxane hydrochloride, a drug that binds iron in the blood, could be administered 30 minutes before the doses of doxorubicin to prevent the formation of free radicals in young patients.
Doxorubicin kills cancer cells by entering their DNA and preventing them from dividing further. “It acts like a roadblock or barrier to their dividing and that kills the cancer cells,” Lipshultz says.
But the drug also damages heart muscle cells by binding with iron in the blood to make free radicals, molecules that have been linked to heart disease and other chronic conditions. “The free radicals are like bullets to your heart tissue,” he says.
They also studied whether dexrazoxane would protect children’s hearts if they were given larger doses of doxorubicin for osteosarcoma, a difficult-to-treat bone cancer.
And they researched using dexrazoxane to protect the hearts of children given two heart-damaging drugs, Herceptin (trastuzumab) and doxorubicin. These are used to treat metastatic osteosarcoma, another hard-to-treat bone cancer.
Lipshultz and his co-workers spent many years following the progression of heart disease in study participants. During that time, they didn’t know which patients as children were given dexrazoxane before the doxorubicin and which were given just doxorubicin.
“But when one study ended after 18 years, the findings were miraculous,” he says. The hearts of patients who received the dexrazoxane were normal.
“As a result of these studies, more kids can be cured of cancer with less toxicity and late effects. It is amazing and it’s the coolest thing because now we can give life where there was death,” he says. “It doesn’t get better than that.”
When it comes to breast cancer, researchers from Memorial Sloan-Kettering Cancer Center in New York issued an important paper at the ASCO meeting. They reported that women who between 1970 and 1986 received radiation to parts of their chests during treatment for childhood cancers had a 24 percent risk of developing breast cancer by age 50.
That compares with the average woman who has a 4 percent chance. And those given larger doses of radiation, like that used to treat Hodgkin’s lymphoma, increased their risks to 30 percent. This becomes particularly critical for women who have the breast cancer type 1 susceptibility protein (BRCA1) gene mutation that is associated with an increased risk of developing breast cancer.
Women treated with chest radiation for childhood cancer who have this gene have more than a 30 percent risk of developing breast cancer by age 50.
The research suggests that female survivors of childhood cancer who received even moderate amounts of chest radiation as children should get mammograms and chest MRIs starting at age 25.
Lamas finds these results potentially lifesaving. He replaced the mitral valve of a young woman 10 years after she was treated for childhood Hodgkin’s lymphoma.
“When I saw these late effects breast cancer results, I realized I had not discussed breast cancer with her. But now I will,” he says.
Talking to patients about potential late effects has to be done in a very matter-of-fact way, he says. “They’ve been through a horrendous, life-changing experience as children and the last thing you want to do is frighten them or bring back the fears that they had,” he adds.
Parents also should get involved in limiting late effects by keeping detailed records of their child’s cancer treatments and making that information part of their youngster’s medical history.
“Even if you’ve just had a lot of diagnostic X-rays to any area of your body, your primary care physician should be aware of those,” Toonkel says.
Lipshultz recommends that if you have cancer treatments in childhood, you should protect yourself with checkups and screenings, be more physically active, eat well, and be educated about possible late effects. “When you get a diagnosis of childhood cancer, you want to be thinking about lifetime risks right from day one,” Lipshultz says. “You want to be in control of your life.”