Abstract
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. 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. 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. 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.
Highlights
Twenty-five adults suffering from primary or recurrent dermatofibrosarcoma protuberans (DFSP) were included from July 2004 to May 2006
Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue sarcoma characterized by progressive local growth of CD34+ spindle cells with a highly infiltrative pattern [1]
Patients The study population consisted of patients with histologically confirmed primary DFSP or local relapse of DFSP, tumor size ≥2 cm, 18 years of age or older; women that were enrolled into this study were taking contraception
Summary
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. Patients The study population consisted of patients with histologically confirmed primary DFSP or local relapse of DFSP, tumor size ≥2 cm, 18 years of age or older; women that were enrolled into this study were taking contraception. The eligibility criteria included WHO performance status of 0 or 1, New York Heart Association class >2, adequate hematologic, hepatic, and renal function, no other evolving tumor, no history of hepatitis C/B and/or HIV 1/2 infection, and no previous treatment with tyrosine kinase inhibitor. Patients provided written informed consent before enrollment in the study. The study was approved by the Paris Saint Louis ethics committee
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
