Imatinib mesylate in 18 advanced chordoma patients

Abstract

9012 Background: We reported (Cancer 2004;101:2086) the antitumor activity of Imatinib mesylate in 6 patients with advanced chordoma treated on an individual basis at the Istituto Nazionale Tumori, Milan, Italy, on biomolecular evidence of potential sensitivity to this agent. Other 12 patients were put on treatment thereafter, up to July 2004, before a currently ongoing Phase II study could be opened. We update/report herein efficacy data on the whole series of these 18 patients. Methods: Eighteen patients with a histological diagnosis of chordoma (originating from sacrum in 13, skull base in 3, and vertebrae in 2) started Imatinib mesylate from August 2002 to July 2004, at the daily dose of 800 mg in 14, and 400 mg in 4. M:F ratio was 9:9. Age was 14–77 (median: 56). Extent of disease was locally advanced in 12, local and metastatic in 6. Median interval from diagnosis was 5 yrs (range: 0–12). KPS was = 0–2 in 9, and = 3 in the remaining patients. Results: Two patients (11%) had a “dimensional response”, with a <50% tumor regression in bidimensional size, while other 11 patients (61%) had radiological signs of “tissue response”, with decreased contrast uptake/enhancement and/or decreased tumor density at CT/MRI, following patterns which in GIST are usually indicative of a tumor response. One patient had only a “functional response”, i.e. a decreased glucose uptake at PET scan against an unchanged radiological aspect. Some degree of subjective improvement was reported in 10 out of 14 symptomatic patients. The actuarial progression-free interval at 1 year was 88%, but 2 patients died with no evidence of tumor progression at 41 and 68 weeks, due to complications of a mostly liquefied, enormous tumor mass. Other two patients died and one stopped therapy early, in the absence of tumor progression. Thus, 11 patients are currently on therapy, after 14–70 weeks from treatment start. Conclusions: On a larger number of patients, we confirm that Imatinib mesylate has antitumor “activity” in chordoma. The potential of major clinical “efficacy” is suggested by the progression-free interval (up to 70+ weeks) seen in surviving patients with a long follow-up. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis