Extra chemo drugs don’t improve treatment of rare bone cancer


A large clinical trial, published this week in The Lancet Oncology, should spare young people with a rare bone cancer from the side effects of too much chemotherapy.

The cancer, called osteosarcoma, is a malignant bone tumor that usually affects teenagers. Current treatments are less effective than doctors and patients would like, so in recent years doctors have sometimes added extra chemotherapy drugs to the standard regimen. A few prior small, non-randomized trials (such as this 1982 study, a 1999 study and a 2011 study) suggested this helped. But the new study, whose senior author is Stanford pediatric oncologist Neyssa Marina, MD, shows that the extra drugs aren’t increasing the success of treatment, and they are causing more side effects.

The study looked at more than 600 patients from 17 countries around the world. It focused on patients whose bone tumors are not completely killed by their initial rounds of chemotherapy, a group whose long-term outcomes tend to be worse. In later rounds of chemo, half of the patients studied were randomized to receive the standard medication regimen, known as MAP (containing the drugs methotrexate, doxorubicin and cisplatin) while the other half got MAP with two extra drugs, ifosfamide and etoposide.

The extra drugs did not increase “event-free survival,” the amount of time before a patient relapses, develops a secondary cancer or dies. Patients receiving the extra drugs did experience more side effects. From our press release about the research:

‘The important message from this data is that adding these two drugs does not improve the outcomes of patients who have poor responses to the initial chemotherapy,’ Marina said. ‘The drugs shouldn’t be added. With them, patients experience more toxicity and more second malignancies.’ The data is already changing pediatric cancer care, she added.

During our conversation about the research, Marina emphasized the need for large, randomized clinical trials, while also acknowledging how hard it is to conduct these studies for rare diseases. Her team at Lucile Packard Children’s Hospital Stanford treats about five or six osteosarcoma patients each year, a typical number for a large pediatric cancer center, and not nearly enough for a trial. To enroll enough patients in the new research, the scientists involved had to persist through the regulatory challenges of making sure their protocol would be approved in 17 different countries, as well as handling the extra logistic complications that come with collecting clinical samples and other data in so many locations.

Now that this trial has concluded, Marina has her eye on the next advance in bone cancer therapy. Again, from our release:

The research team believes the next advances in osteosarcoma therapy will require a precision-medicine approach that finds and targets specific cancer-causing gene mutations in different patients, Marina said.

Via Scope
X-ray image of osteosarcoma in the arm by bc the path


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