Imatinib in advanced chordoma: A retrospective case series analysis.
BACKGROUND
Imatinib showed activity in 50 chordoma patients treated within a Phase II study. In that study, 70% of patients remained with stable disease (SD), median progression free survival (PFS) was 9 months and median overall survival (OS) was 34 months. We now report on a retrospective series of PDGFB/PDGFRB positive advanced chordoma patients treated with imatinib as a single agent within a compassionate-use programme at Istituto Nazionale Tumori, Milan, Italy (INT) between August 2002 and November 2010, when the programme was closed.


METHODS
48 patients were consecutively treated with imatinib 800 mg/d. All patients had inoperable and progressive disease before starting imatinib. Demographics, treatment duration, toxicity and response rate by Response Evaluation Criteria in Solid Tumors (RECIST) were retrospectively recorded.


RESULTS
The median duration of therapy was 7 months (1-46.5). No patient is on therapy at present. 46 patients were evaluable for response. No partial responses were detected. Best response was: stable disease 34 (74%), progressive disease 12 (26%). At a median follow-up of 24.5 months (0.5-117), median PFS was 9.9 months (95% confidence interval (CI) 6.7-13). Eight patients (16.5%) remained on therapy >18 months and 10 patients (21%) remained progression-free >18 months. Median OS was 30 months (95% CI 20-40), with 24 (50%) patients dead at the time of the present analysis.


CONCLUSIONS
We confirm the activity of imatinib in locally advanced and metastatic chordoma, in terms of >70% tumour growth arrest in previously progressive patients. Median duration of response lasted almost 10 months, with >20% of patients progression-free at 18+ months.
Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy. Electronic address: nadiahindi83@gmail.com.
Nadia
N
Hindi
Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Paolo G
PG
Casali
Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Carlo
C
Morosi
Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Antonella
A
Messina
Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Elena
E
Palassini
Department of Pathology and Molecular Biology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Silvana
S
Pilotti
Department of Pathology and Molecular Biology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Elena
E
Tamborini
Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Stefano
S
Radaelli
Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Alessandro
A
Gronchi
Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, 20133 Milan, Italy.
Silvia
S
Stacchiotti
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002817:Chordoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D057176:Compassionate Use Trials; D018572:Disease-Free Survival; D004487:Edema / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D020574:Proto-Oncogene Proteins c-sis; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta
Chemotherapy; Chordoma; Imatinib; Metastasis; Sarcoma; Targeted therapy