Fiche publication
Date publication
juin 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Pr AUBIN François
Tous les auteurs :
Kerob D, Porcher R, Verola O, Dalle S, Maubec E, Aubin F, D'Incan M, Bodokh I, Boulinguez S, Madelaine-Chambrin I, Mathieu-Boue A, Servant JM, de Kerviler E, Janin A, Calvo F, Pedeutour F, Lebbe C
Lien Pubmed
Résumé
AIMS: The treatment of dermatofibrosarcoma protuberans (DFSP) involves wide local excision with frequent need for reconstructive surgery. A t(17;22) translocation resulting in COL1A1-PDGFB fusion is present in >95% of cases. Certain patient observations and a report on nine patients suggest that imatinib mesylate, targeting platelet-derived growth factor receptor beta, has clinical potential in DFSP. The primary aim of this phase II multicenter study was to define the percentage of clinical responders (Response Evaluation Criteria in Solid Tumors) to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. The secondary aims were to determine tolerance, objective response from imaging results (ultrasound and magnetic resonance imaging), and pathologic responses observed in sequential tissue specimens. PATIENTS AND METHODS: A two-stage flexible design was used with interim analysis after the recruitment of six patients. Twenty-five adults suffering from primary or recurrent DFSP were included from July 2004 to May 2006. RESULTS: The COL1A1-PDGFB fusion gene was detected in 21 out of 25 patients following fluorescence in situ hybridization analysis (two cases were noninformative). A clinical response was achieved in nine (36%) patients (95% confidence interval, 18.9-57.5). The median relative tumoral decrease was 20.0% (range, -12.5 to 100). Apart from expected grade 1 or 2 side effects, we observed one grade 3 neutropenia, one grade 3 maculopapular rash, and one grade 4 transient transaminitis. CONCLUSION: Our results support the use of imatinib in a neoadjuvant setting in nonresectable DFSP, or when surgery is difficult or mutilating. These results will be useful for setting hypotheses in the evaluation of new drugs to treat primary or secondary resistance to imatinib.
Référence
Clin Cancer Res. 2010 Jun 15;16(12):3288-95
