Large randomized EORTC trial contributes to the evidence on adjuvant chemotherapy in high risk soft tissue sarcomas

An EORTC Soft Tissue and Bone Sarcoma Group / National Cancer Institute of Canada (NCIC) Clinical Trials Group Sarcoma Disease Site Committee clinical trial has made a significant contribution towards understanding adjuvant chemotherapy in treating resected high risk soft tissue sarcomas in an article reported in Lancet Oncology.

Soft-tissue sarcomas are difficult to treat. They can develop anywhere in the body and have over fifty different histological subtypes, yet they comprise less than 1% of malignancies. The standard treatment for localized disease is surgery, often combined with radiotherapy, but the idea of using adjuvant chemotherapy to improve survival rates in high grade soft tissue sarcoma has been a subject of particular interest. The randomized EORTC trial 62931 was designed to assess adjuvant chemotherapy with doxorubicin, ifosfamide and lenograstim, in resected high grade tumors.

Dr. Penella Woll of the Weston Park Hospital in Sheffield, United Kingdom, and Study Coordinator for this trial says, “This trial represented a sustained effort from an international collaborative group over almost 20 years. Our data significantly expand the available evidence on adjuvant chemotherapy in resected soft-tissue sarcoma.”

A total of 351 patients with histologically proven, non-metastatic intermediate or high grade (Trojani grade II or III) soft tissue sarcoma that had been definitively resected were recruited from 36 sarcoma centers in Europe and Canada between 1995 and 2003 and randomized to control (observation), 176 patients, or adjuvant chemotherapy, 175 patients. All patients received radiotherapy if the resection was marginal or the tumor recurrent.

Adjuvant chemotherapy was well tolerated, and 79.8% of patients who began adjuvant chemotherapy completed the treatment. There were no toxic deaths, but 9.8% of the patients experienced grades 3 or 4 fever or infection. Radiotherapy was administered to 129 patients (73.5%) in each arm.

The five year survival rate was 67% with no significant difference in overall survival (OS) (hazard ratio (HR) 0.94, 95% confidence intervals (CI) 0.68, 1.31, p = 0.717) or relapse free survival (RFS) (HR 0.91, 95% CI 0.67, 1.22, p = 0.508) between the treatment arms. Furthermore, no subgroup was identified to benefit from adjuvant chemotherapy.

The addition of adjuvant chemotherapy with doxorubicin and ifosfamide to the standard treatment of surgery and radiotherapy in soft tissue sarcoma shows no benefit in OS or RFS.

John Bean