Drug Derived From Sea Squirt Shows Potent Anti-tumour Activity

Dr Federica Grosso, Sarcoma Unit, Instituto Nazionale Tumori, Milan, Italy, and colleagues in sarcoma centres in Boston, London, Lyon and Paris, did a retrospective study of the effect of trabectedin (derived from Ecteinascidia Turbinata) on patients with advanced pre-treated myxoid liposarcomas, a subtype of the liposarcoma group of cancers associated with specific chromosomal mutations.

They found that of 51 patients with myxoid liposarcomas given trabectedin as part of a compassionate-use programme, two saw their tumours disappear completely (complete response) while a further 24 saw the longest diameter of their tumour shrink by at least 30% (partial response), representing an overall response rate of 51%. Previous studies of trabectedin have shown response rates no higher than 20%. Of these 26 patients that responded, 23 had undergone radiological review of their tumours. The authors showed 17 of these 23 had also experienced reduced tumour density prior to the shrinkage or disappearance of their tumour.

In addition, the progression free-survival rate at six months was 88%, whereas previous studies in all soft tissue sarcomas have placed this figure closer to 20%. Median progression-free survival was 14 months.

The authors say: “If the results of this analysis are reproduced in ongoing prospective studies, myxoid sarcoma would represent a uniquely sensitive subgroup to trabectedin treatment in the heterogeneous family of soft-tissue sarcoma.”

Surgical removal is the mainstay of current treatment regimens for soft-tissue sarcoma, but despite this around half of patients develop distant metastases (secondary tumours) and die. Certain drugs, such as anthracyclines and ifosfamide, have shown response rates of 20-40%, but new drugs are needed.

The authors say that a compassionate-use programme of trabectedin treatment remains ongoing. They conclude: “This analysis has resulted in the initiation of two prospective studies to assess the role of trabectedin in the treatment of myxoid liposarcoma in the pre-operative and metastatic settings. Furthermore, the selective mechanism of action for trabectedin in this translocation-related sarcoma is being studied.”

This research was published early online and in the July edition of The Lancet Oncology.