Imatinib Mesylate in Desmoplastic Small Round Cell Tumour

Introduction Desmoplastic small round cell tumor (DSRCT) is a very rare and aggressive mesenchymal neoplasia with an extremely poor prognosis. The typical translocation t(11;22) determines the overexpression of PDGF-Rα and β, responsible of clinical stromal fibrosis reaction constantly detected in abdominal lesions. We investigated the role of imatinib, as tyrosine kinase inhibitor of PDGF-R, in DSRCT. Patients and methods From August 2005 to June 2009 we enrolled patients (pts) with histologically proven diagnosis of DSRCT, refractory to conventional treatment. Inclusion criteria comprised immunohistochemical positivity of imatinib targets (PDGF-Rα and β). Treatment consisted of imatinib 400 mg p.o. daily. Primary endpoint of the study was objective response rate. Secondary endpoint was safety and tolerability assessment. Results Of the 13 enrolled patients, 8 pts were evaluable for response (4 screening failure and 1 never treated). Median age was 20 years (range, 9-32). M/F ratio was 7/1. ECOG PS was 0 in 6 pts. Median time from diagnosis was 24.5 months (range, 6-148). 75% of pts had metastatic disease. The primary site was abdominal-pelvic for all pts. PDGFRα and β were expressed with an heterogeneous intensity pattern. Objective responses at first radiological evaluation at 3 months were: stable disease in one pt (12.5%) and progressive disease in 7 (87.5%) pts. Treatment-related adverse events were G1-2 nausea/vomiting, fatigue and periorbital oedema. Conclusions In our limited case series, imatinib showed no efficacy in the treatment of DSRCT pts unresponsive to conventional therapy, despite molecular-based selection of pts. Probably to identify responder pts, it is necessary a more complex evaluation comprehensive of both levels of expression and activation of PDGFRα and β. Furthermore, enrolled pts were affected by advanced refractory disease, probably less responsive to target therapies. It would be hopeful a global effort to define a new combined approach based on the association of conventional chemotherapy and biological drugs. Disclosure C. Gnocchi: Novartis Patient Advocacy Manager. All other authors have declared no conflicts of interest.