title: Phase II study of imatinib in advanced chordoma.
abstract: OBJECTIVE
  To explore the antitumor activity of imatinib in patients with advanced platelet-derived growth factor β (PDGFB)/PDGF receptor β (PDGFRB)-positive chordomas.
  
  
  METHODS
  In a collaborative Italian-Swiss, prospective, phase II clinical study conducted from November 2004 through April 2006, 56 patients with advanced PDGFB and/or PDGFRB chordoma received 800 mg/d of imatinib until progression. The primary end point was the overall tumor response rate (ORR), defined by RECIST. Secondary, exploratory end points included tissue response (ie, changes in tumor density or signal intensity/contrast enhancement, and/or [18F]-fluorodeoxyglucose positron emission tomography [PET] uptake), overall survival, progression-free survival (PFS), and pain score.
  
  
  RESULTS
  Among 50 patients evaluable by RECIST, the best response was one partial response (PR) obtained at 6 months (ORR, 2%). There were 35 patients with stable disease (SD, 70%) and a 64% clinical benefit rate (ie, RECIST complete response + PR + SD ≥ 6 months). A minor dimensional response (< 20%) was detected in nine patients. A maximum standard uptake value decrease ≥ 25% was observed in 10 (39%) of 26 patients evaluable for PET response at 3 months. Changes in the Brief Pain Inventory score were consistent with the response assessment. Median PFS (intention-to-treat population, 56 patients) was 9 months. No unexpected toxicities were observed.
  
  
  CONCLUSIONS
  This is the largest phase II study in chordoma to date. It confirms anecdotal evidence that imatinib has antitumor activity in this orphan disease, and therefore, it is worth further investigation.
authors.affiliation: Fondazione Istitutodi Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy. silvia.stacchiotti@istitutotumori.mi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Stacchiotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Longhi
authors.forename: Virginia
authors.initials: V
authors.lastname: Ferraresi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grignani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Comandone
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Alexia
authors.initials: A
authors.lastname: Bertuzzi
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Messina
authors.forename: Carlo
authors.initials: C
authors.lastname: Spreafico
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Paola
authors.initials: P
authors.lastname: Amore
authors.forename: Vincenza
authors.initials: V
authors.lastname: Vinaccia
authors.forename: Paolo Giovanni
authors.initials: PG
authors.lastname: Casali
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D015153:Blotting, Western; D002817:Chordoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D007558:Italy; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015996:Survival Rate; D013557:Switzerland; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta