Large study shows benefits of single agent doxorubicin therapy for sarcoma

Doubts over the best standard treatment for metastatic soft tissue sarcoma have been put to rest thanks to a large international, randomised clinical trial led by a scientist at The Institute of Cancer Research, London.

This study investigated the treatment of patients with advanced soft tissue sarcoma, comparing single-agent doxorubicin, which remains the gold standard in many countries, with a very intensive combination of doxorubicin and the alkylating agent ifosfamide, an agent also used routinely in sarcoma treatment.  

The study was conducted by the EORTC Soft Tissue and Bone Sarcoma Group, and led by Professor Ian Judson, professor of cancer pharmacology at The Institute of Cancer Research (ICR) and head of the sarcoma unit at The Royal Marsden NHS Foundation Trust. The new results were presented at the European Society for Medical Oncology conference in Vienna on 1 October.  

Previous studies that compared single-agent and combination treatments had shown no benefit for combination therapy, but concern that the dose of ifosfamide used in earlier studies was too low to be effective resulted in serious doubts concerning these conclusions and prompted the new trial. In the new study the dose of doxorubicin was the same in both arms and the ifosfamide dose was two-fold higher than in previous comparative studies.  A total of 455 patients from eight European countries and Canada, aged up to 60 years, were treated, half of whom received the single agent and half the combination treatment.

The study found that patients given the single treatment lived for just as long, and had a lower risk of significant side-effects, than those receiving the combination. The combination treatment did block cancer growth for longer than the single agent treatment (7.4 months versus 4.6 months), and was more likely to cause tumour shrinkage (24 per cent versus 13.2 per cent), but after two years there was no difference in survival rates between the two groups.

Patients taking the combination treatment were also much more likely to suffer side-effects including febrile neutropenia (fever associated with a reduction in white blood cells that normally help fight infection) and anaemia (a reduction in red blood cells that can cause a variety of symptoms including fatigue and weakness).

Professor Judson said: “The results will help put to rest any remaining doubts over the best way to treat the majority of patients with soft tissue sarcoma, and provide reassurance to patients that they are receiving the best possible care. Not only does single-agent doxorubicin remain a suitable standard therapy, but it continues to be an appropriate comparator for future randomised trials.”

For a small number of patients for whom tumour shrinkage is critical – for example patients whose tumours could potentially still be removed by surgery if they were smaller, or those whose symptoms could only be relieved by significantly reducing the size of a tumour – the more intensive treatment may be justified, but doctors would need to carefully weigh up the potential benefit against the substantially increased risk of side-effects. It should also be noted that the study only included patients up to the age of 60, owing to the increased risk of serious side-effects in older patients.