title: Imatinib mesylate in chordoma.
abstract: BACKGROUND
  To the authors' knowledge, no effective medical therapy currently is available for advanced chordoma. Imatinib mesylate is a tyrosine kinase inhibitor targeting platelet-derived growth factor receptor-beta (PDGFRB), BCR-ABL, and KIT.
  
  
  METHODS
  Six patients with advanced chordoma were treated with imatinib mesylate at a dose of 800 mg daily. In all patients, the tumor was found to be positive for PDGFRB, and in four patients PDGFRB was shown to be phosphorylated/expressed.
  
  
  RESULTS
  After a treatment period of > or = 1 year, overt tumor liquefaction was evident on computed tomography (CT) scan in the first patient. In previous months, a decrease in contrast enhancement on magnetic resonance imaging (MRI) and a decrease in glucose uptake on positron emission tomography (PET) were detected. Similar signs on MRI and PET were observed in subsequent patients, who had a shorter treatment period. One of these patients initially was removed from therapy and then was readmitted to therapy because of difficulties with regard to tumor response assessment; 1 month after the reinitiation of therapy, an overt decrease in tumor density was visible on CT scan in this patient. In four of five symptomatic patients, a subjective improvement was observed early in the course of treatment. The first patient died after 17 months, with a sizeable, mostly liquefied mass. Another patient died early, apparently of unrelated causes. The remaining patients were on therapy at the time of last follow-up.
  
  
  CONCLUSIONS
  Imatinib mesylate has been found to have antitumor activity in patients with chordoma. This activity might be mediated by inactivation of PDGFRB. Tumor response manifests through patterns that are similar to those observed in patients with gastrointestinal stromal tumors who respond to molecular-targeted therapy, but evolves more slowly. The benefit to the patient entailed by this pattern of tumor response in chordoma needs to be elucidated, but may be limited in the presence of significant local disease.
authors.affiliation: Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. paolo.casal@stitutotumori.mi.it
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.forename: Antonella
authors.initials: A
authors.lastname: Messina
authors.forename: Silvia
authors.initials: S
authors.lastname: Stacchiotti
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Flavio
authors.initials: F
authors.lastname: Crippa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Rosaria
authors.initials: R
authors.lastname: Orlandi
authors.forename: Carla
authors.initials: C
authors.lastname: Ripamonti
authors.forename: Carlo
authors.initials: C
authors.lastname: Spreafico
authors.forename: Raffaello
authors.initials: R
authors.lastname: Bertieri
authors.forename: Rossella
authors.initials: R
authors.lastname: Bertulli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Colecchia
authors.forename: Elena
authors.initials: E
authors.lastname: Fumagalli
authors.forename: Angela
authors.initials: A
authors.lastname: Greco
authors.forename: Federica
authors.initials: F
authors.lastname: Grosso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Olmi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002817:Chordoma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta