Preoperative radiation therapy and iododeoxyuridine for large retroperitoneal sarcomas

Local failure is frequent after conventional therapy for patients with retroperitoneal sarcomas. A Phase I/II multimodality approach was used, combining iododeoxyuridine (IdUrd) and radiation therapy, followed by attempted surgical resection, with the goal of improving local control.

Patients with retroperitoneal sarcomas were treated with three to five consecutive cycles of treatment. Each 14-day cycle consisted of a continuous intravenous infusion of IdUrd on days 1-5, twice a day radiation therapy (1.25 Gy/fraction) on days 8-12, and a break on day 13 and 14. Surgical resection was attempted after three or five cycles. Patients resected after three cycles received an additional two cycles of treatment with radiation directed to the tumor bed. IdUrd dose was escalated in Phase I fashion (1000 mg/m2/day, 1333 mg/m2/day, and 1600 mg/m2/day). The median potential follow-up was 31 months.

Sixteen patients (13 with high grade tumors) were treated. The median maximum tumor size was 17 cm. Resection margins were negative in four patients, microscopically positive in four patients, and grossly positive in three patients. Five patients were not resected. The only grade 4 acute toxicity observed was vomiting which occurred in three patients receiving upper abdominal radiation. Postsurgical and long-term complications were rare. Median survival overall and for resected patients were 18 and 32 months, respectively. Local control was observed in three out of four patients with negative margins (9, 40+, and 51+ months), two out of four patients with microscopically positive margins (4 and 22 months), and one out of three patients with grossly positive margins (46+ months). The overall freedom from local progression was 45% at 24 months.

Retroperitoneal sarcomas can be resected after preoperative radiation therapy and IdUrd, with encouraging local control in patients resected with negative or microscopically positive margins. The recommended dose using this drug and radiation schedule appears to be 1600 mg/m2/day, which will form the basis for a Phase II trial.