Finding a better treatment for bone cancer

Megan Martin is an active, outgoing teen with a mega-watt smile. The 18-year-old high school senior from Johnston, Iowa, is an avid reader of the classics who's on the academic decathlon and the mock trial teams at Johnston High School, and is a member of the University of Iowa Stead Family Children’s Hospital youth council. She's also a big swimmer—it's such a passion that she's considering a career in marine biology.

But a shocking discovery in February 2011 interrupted her life and confronted Megan with a frightening medical diagnosis that most teens never have to think about, much less deal with.

Megan had knee pain that she thought might be tendonitis, but an X-ray showed a bony erosion in her femur and a follow-up MRI scan found a tumor about three inches above her knee.

Megan's doctor referred her to UI Stead Family Children’s Hospital, where teams of specialists have long-standing expertise in treating all forms of pediatric cancer.

There, a biopsy showed that Megan had osteosarcoma, a rare cancer that nonetheless is the most common type of bone cancer and usually occurs in adolescence when the bones are growing the fastest.

Megan remembers feeling shocked and numb when she was given the diagnosis.

"I didn't really have any feelings at that time," she says. "I didn't even know then that you could get cancer in your bones, so it was really shocking."

Despite that initial shock, Megan's positive nature quickly reasserted itself.

"I was just focused on getting started with the treatment and getting done and getting on with my life," she says.

Strength in numbers

Megan's treatment, recommended by UI Stead Family Children’s Hospital oncologist Raymond Tannous, MD, is a phase 3 clinical trial testing whether newer chemotherapy combinations can improve outcomes for patients with osteosarcoma.

The study is coordinated by the international Children's Oncology Group (COG) and involves multiple institutions across the United States and Europe. According to Tannous, the UI’s involvement in this clinical trials network is a huge benefit to Iowa patients affected by osteosarcoma.

"Cancer in children is actually very rare," Tannous says. "So, it is impossible for one center to have enough cases to mount a meaningful study. To do that, cancer centers all over the country, Canada, Europe, and Australia got together and developed this and other similar trials. It would not be possible to do a clinical trial if we were on our own and only involved Iowa patients—the numbers would be too small to determine if a treatment is effective. By being part of these worldwide trials and networks, our Iowa patients also have better access to new treatments, including investigational drugs that are only available through a study.

"In addition, when you have a study that has been developed by experts from all over the country or even the world, you can bring all that brain power together to help your patients. It is a major plus for our patients," he says.

The study in which Megan is participating will determine whether adding new chemotherapy drugs to the current standard treatment produces better results for patients with osteosarcoma.

All the study participants start off with the same treatment—10 weeks of chemotherapy to shrink the tumor followed by surgery to remove the tumor. Then a pathology team determines how much of the tumor was killed by the chemo. Patients whose tumors are mostly killed either continue with a second round of chemotherapy, which is the current standard treatment, or they get the chemotherapy plus another drug that may further improve outcomes.

For patients whose tumors are more resistant to the initial chemo, half will also continue with standard therapy and half will add two powerful chemotherapy drugs to that treatment. Studies have suggested, but not proven, that these drugs may help patients whose tumors are more resistant to the pre-surgery treatment.

A boost from new therapies

Megan's doctors determined that her tumor had a poor response to the initial chemotherapy.

"Ninety-five percent kill is considered a good response and my tumor only got a 70 percent," Megan explains. "That is a C grade, which I think is still passing," she jokes.

The fact that the tumor was not completely killed by the initial therapy put Megan in the group of patients getting standard therapy plus the two additional chemotherapy drugs.

Tannous is excited about the current study.

"This is a combination I really like, because I have seen cases where patients who appeared to have very poor chances of surviving have been helped by this therapy," he says. "But these were anecdotal cases and don't prove that the treatment is definitely more effective than standard treatment. The COG is now asking in a systematic way, does this therapy improve the cure rate for patients?"

"I do think it is important to do clinical trials," Megan adds. " I think it is important to continue to look at new things and make things better and more effective."

The trial Megan is in is a phase 3 study, which is the final stage of clinical testing for a new treatment. Megan and her family are acutely aware of all the experimental work and earlier clinical trials that have laid the foundation for this final trial.

"We are really grateful to the families who came before us who were in the earlier phases," says Sarah Martin, Megan's mom.

Even as she undergoes her treatment, Megan's sights remain firmly fixed on the future.

"I'll graduate in May then I'll go to college probably here in Iowa—UI, ISU or Drake," she says. "I'd like to do marine biology. I love the water—I think fish and sea turtles and coral reefs are cool—and I'd love to scuba dive every day."

Tannous is confident that this systematic clinical trial will provide clear answers and help advance treatment for all patients. He also has a deep admiration for Megan's attitude as she goes through the treatment.

"On a personal level Megan is incredibly sweet, but on the mental level of fighting her disease, she is one of the toughest individuals you could meet," Tannous says. "It's a really fantastic combination, a winning combination I would say."