Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patients.

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.

Protocolisation, use and development of anti-cancer drugs in the context of T2A (case-mix based payment system) set-up.

Drugs used in oncology represent more than half of the innovative and costly drugs which are not covered by a Group Homogène de Soins (DRG type classification) within the context of the case-mix based payment system (termed T2A). For these drugs, good practice reference guidelines have been drawn up by scientific societies and registration agencies. Recognised indications, relevant indications and situations where the treatment should not be prescribed are defined by the National Institute of Cancer. The reference guidelines should lead towards the good use of these drugs and allow the sick funds to control prescriptions. They should evolve with time, which means that bibliographic monitoring and independent expert opinion is necessary to update them as science provides new data. Manufacturers are involved in this process which in no case should undermine developmental efforts leading to registration. The objective of this protocolisation is to allow all patients early and legitimate access to drugs representing real therapeutic progress. These reference guidelines should be integrated into the life-cycle of a drug and should give rise to new developments allowing the good use of cancer products in situations which have been properly validated.

Protocolisation, Use and Development of Anti-Cancer Drugs in the Context of T2A (Case-Mix Based Payment System) Set-Up.

Drugs used in oncology represent more than half of the innovative and costly drugs which are not covered by a Group Homogène de Soins (DRG type classification) within the context of the case-mix based payment system (termed T2A). For these drugs, good practice reference guidelines have been drawn up by scientific societies and registration agencies. Recognised indications, relevant indications and situations where the treatment should not be prescribed are defined by the National Institute of Cancer. The reference guidelines should lead towards the good use of these drugs and allow the sick funds to control prescriptions. They should evolve with time, which means that bibliographic monitoring and independent expert opinion is necessary to update them as science provides new data. Manufacturers are involved in this process which in no case should undermine developmental efforts leading to registration. The objective of this protocolisation is to allow all patients early and legitimate access to drugs representing real therapeutic progress. These reference guidelines should be integrated into the life-cycle of a drug and should give rise to new developments allowing the good use of cancer products in situations which have been properly validated.