A new European study does not support administration of intensified doxorubicin and ifosfamide for palliation of advanced soft tissue sarcoma. However, use of the combined treatment is justified if the objective is to shrink the tumor or relieve symptoms.
For some 30 years, patients with soft tissue sarcomas have been treated with doxorubicin and ifosfamide, but few studies have examined whether doxorubicin should be administered alone or in combination with ifosfamide. The European Organization for Research and Treatment of Cancer (EORTC) trial 62012 evaluated whether the combination of doxorubicin and ifosfamide improved survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.
“Our results show that the combination chemotherapy did not improve overall survival,” said study coordinator Ian Judson, MD, of the Royal Marsden Hospital in London, England. “If the goal of treatment is to control the disease, then administering doxorubicin alone is appropriate. If the goal is to shrink the tumor before another intervention or to relieve symptoms, then combination treatment is justifiable.”
The intergroup phase III randomized controlled trial was conducted at 38 hospitals in 10 countries from April 2003 to May 2010. Patients with unresectable, locally advanced, or metastatic high-grade soft-tissue sarcoma age 18 to 60 years received doxorubicin alone (228 patients) or intensified doxorubicin plus ifosfamide (227 patients, combination group) as first-line treatment.
No significant difference was observed in median overall survival (12.8 months in the doxorubicin alone group and 14.3 months in the combination group). Median progression-free survival was significantly higher in the combination group (7.4 months) than the doxorubicin alone group (4.6 months). More patients in the doxorubicin and ifosfamide group than in the doxorubicin alone group had an overall response (26% versus 14%).
Grades 3 and 4 toxic effects were more common in the combination group than in the doxorubicin alone group: leukopenia (43% versus 18%), neutropenia (42% versus 37%), febrile neutropenia (46% versus 13%), anemia (35% versus 5%), and thrombocytopenia (33% versus <1%).
Judson said that better treatments are needed for patients with this disease. This study was published in The Lancet Oncology (2014; doi:10.1016/S1470-2045(14)70063-4).
EORTC trial 62012 was supported by Cancer Research UK, EORTC Charitable Trust, United Kingdom National Health Service, Canadian Cancer Society Research Institute, and an Educational Grant from Amgen.