More Chemotherapy Does Not Lead to Improved Outcomes for Patients With Osteosarcoma

Results from a large clinical trial argue against the inclusion of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma due to increasing toxicity and no improvement in event-free survival.

Osteosarcoma is a form of bone cancer that often presents in teenagers. Currently, treatments for the disease are limited and offer little benefit; so, doctors and other health care providers have looked at whether adding extra chemotherapy drugs to the standard care regimen could improve outcomes.
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In the EURAMOS-1 clinical trial led by Neyssa Marina, MD, Lucile Packard Children’s Hospital Stanford (Palo Alto, CA), investigators sought to determine whether intensified postoperative chemotherapy for patients not responding well to preoperative chemotherapy could improve event-free survival among those with high-grade osteosarcoma.

Between April 14, 2005 and June 30, 2011, a total of 2260 patients aged 40 years or younger were enrolled in the trial and randomly assigned to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP), or MAP plus ifosfamide and etoposide (MAPIE). The primary outcome measure was event-free survival measured in the intention-to-treat population.

Of 618 patients characterized as having poor response, 310 were assigned to receive MAP and 308 were treated with MAPIE. Median follow-up was 62.3 months and 61.1 months for each group, respectively. There were a total of 307 event-free survival events reported (101 in the MAP group versus 92 in the MAPIE group). However, investigators found that event-free survival did not differ significantly between the treatment groups.

In addition, patients receiving MAPIE tended to have more grade 3-4 adverse events, commonly reported as neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE).

Thus, researchers concluded that results from their trial did not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma, due to an associated increase in toxicity without any significant improvement in event-free survival. Additional trials and new treatment strategies are needed to improve outcomes in this patient population.