Imatinib for the treatment of aggressive fibromatosis (desmoid tumors) failing local treatment. A phase II trial of the French Sarcoma Group

Abstract

9516 Background: Background: Aggressive fibromatosis/desmoid tumors (AF/DT) are rare tumors with loco regional spreading. Few options are available when local treatments have failed. Although cytotoxic agents, hormonal treatment have been reported to induced responses and tumor control in some patients, only few prospective phase II trials have been reported in the literature. Recently, antitumor activity of imatinib in AF/DT was reported. We report a phase II trial of imatinib in AF/DT after failure of local treatment options. Methods: Pts ≥ 18 years with advanced AF/DT from all sites in whom neither surgery nor radiotherapy was possible were eligible. The principal inclusion criterias were: disease not amenable to surgery and/or radiation with curative intent, systemic pre-treatments allowed and presence of a measurable lesion with evidence of progression. Imatinib was given at the dose of 400 mg/d and increased to 800 mg/d if progression. Primary endpoint was the rate of progression free at 3 months. A two stages Simon‘s optimal design was used with p0=10%, p1=30%, α=0.05 and 90% power. 18 pts were scheduled to be recruited in the first stage for a total of 35 evaluable pts. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. The median age was 40 years (range 20–72) with 26% males. Primary sites were extra abdominal, mesenteric, abdominal wall in 79, 15, and 6% respectively. 15% patients had not been operated previously and 17% undergone radiotherapy. Prior systemic treatments were: NSAID, hormonal therapy or chemotherapy in 34, 46 and 23%, respectively. Median treatment duration was 4 months (range 0–12). No G4 toxicity was reported. Toxicities (G1–3) were notified for 30 pts including asthenias (70%), nauseas (53%), diarrheas, oedema (40%). G3 toxicities were abdominal pain (10%), rash, nausea, vomiting and asthenia (7%). At 3 months, 22 pts (55%) were evaluable with 1 CR, 17 SD and 4PD. As of December 2005, 7 of the 40 pts had progressed. After progression, dose was stopped in 2 pts and increased to 800mg in 5 pts with 2 tumor control following dose-escalation. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT in whom no local treatment option was available. [Table: see text]