Imatinib mesylate in chordoma.
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.
Casali
Paolo G
PG
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
Messina
Antonella
A
Stacchiotti
Silvia
S
Tamborini
Elena
E
Crippa
Flavio
F
Gronchi
Alessandro
A
Orlandi
Rosaria
R
Ripamonti
Carla
C
Spreafico
Carlo
C
Bertieri
Raffaello
R
Bertulli
Rossella
R
Colecchia
Maurizio
M
Fumagalli
Elena
E
Greco
Angela
A
Grosso
Federica
F
Olmi
Patrizia
P
Pierotti
Marco A
MA
Pilotti
Silvana
S
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
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta