Imatinib mesylate in chordoma

被引:191
作者
Casali, PG
Messina, A
Stacchiotti, S
Tamborini, E
Crippa, F
Gronchi, A
Orlandi, R
Ripamonti, C
Spreafico, C
Bertieri, R
Bertulli, R
Colecchia, M
Fumagalli, E
Greco, A
Grosso, F
Olmi, P
Pierotti, MA
Pilotti, S
机构
[1] Ist Nazl Studio & Cura Tumori, Dept Canc Med, Adult Sarcoma Med Oncol Unit, I-20133 Milan, Italy
[2] Ist Nazl Studio & Cura Tumori, Dept Diagnost Imaging & Radiotherapy, Radoidiagnost Unit 1, I-20133 Milan, Italy
[3] Ist Nazl Studio & Cura Tumori, Dept Pathol, Pathol Unit C, I-20133 Milan, Italy
[4] Ist Nazl Studio & Cura Tumori, Dept Diagnost Imaging & Radiotherapy, Nucl Med Unit, I-20133 Milan, Italy
[5] Ist Nazl Studio & Cura Tumori, Dept Surg, Melanoma Sarcoma Unit, I-20133 Milan, Italy
[6] Ist Nazl Studio & Cura Tumori, Dept Expt Oncol & Labs, Mol Targets Unit, I-20133 Milan, Italy
[7] Ist Nazl Studio & Cura Tumori, Dept Anaesthesiol Intens Care & Paliat Care, Rehabil & Palliat Care Unit, I-20133 Milan, Italy
[8] Ist Nazl Studio & Cura Tumori, Dept Diagnost Imaging & Radiotherapy, Radiodiagnost Unit 2, I-20133 Milan, Italy
[9] Novartis Pharmaceut, Clin Dev Div, Dept Oncol, Driggio, Varese, Italy
[10] Ist Nazl Studio & Cura Tumori, Radiotherapy Unit 1, I-20133 Milan, Italy
[11] Ist Nazl Studio & Cura Tumori, Dept Pathol, Pathol Unit A, I-20133 Milan, Italy
[12] Ist Nazl Studio & Cura Tumori, Dept Expt Oncol & Labs, Mol Mech Tumor Growth & Progress Unit, I-20133 Milan, Italy
[13] FIRC Inst Mol Oncol, Milan, Italy
关键词
chordoma; imatinib mesylate; tyrosine kinase inhibitor; platelet-derived growth factor receptor-beta (PDGFRB); response;
D O I
10.1002/cncr.20618
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 greater than or equal to 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. (C) 2004 American Cancer Society.
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收藏
页码:2086 / 2097
页数:12
相关论文
共 26 条
[1]  
[Anonymous], 2002, PATHOLOGY GENETICS T
[2]   CHORDOMA - NATURAL-HISTORY AND TREATMENT RESULTS IN 33 CASES [J].
AZZARELLI, A ;
QUAGLIUOLO, V ;
CERASOLI, S ;
ZUCALI, R ;
BIGNAMI, P ;
MAZZAFERRO, V ;
DOSSENA, G ;
GENNARI, L .
JOURNAL OF SURGICAL ONCOLOGY, 1988, 37 (03) :185-191
[3]   Chordoma: Natural history and results in 28 patients treated at a single institution [J].
Baratti, D ;
Gronchi, A ;
Pennacchioli, E ;
Lozza, L ;
Colecchia, M ;
Fiore, A ;
Santinami, M .
ANNALS OF SURGICAL ONCOLOGY, 2003, 10 (03) :291-296
[4]  
BENJAMIN RS, 2003, P AN M AM SOC CLIN, V22, P816
[5]  
Bergh P, 2000, CANCER-AM CANCER SOC, V88, P2122, DOI 10.1002/(SICI)1097-0142(20000501)88:9<2122::AID-CNCR19>3.0.CO
[6]  
2-1
[7]  
CHOI H, 2003, P AN M AM SOC CLIN, V22, P819
[8]   Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base [J].
Debus, J ;
Schulz-Ertner, D ;
Schad, L ;
Essig, M ;
Rhein, B ;
Thillmann, CO ;
Wannenmacher, M .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2000, 47 (03) :591-596
[9]   Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors [J].
Demetri, GD ;
von Mehren, M ;
Blanke, CD ;
Van den Abbeele, AD ;
Eisenberg, B ;
Roberts, PJ ;
Heinrich, MC ;
Tuveson, DA ;
Singer, S ;
Janicek, M ;
Fletcher, JA ;
Silverman, SG ;
Silberman, SL ;
Capdeville, R ;
Kiese, B ;
Peng, B ;
Dimitrijevic, S ;
Druker, BJ ;
Corless, C ;
Fletcher, CDM ;
Joensuu, H .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (07) :472-480
[10]   Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. [J].
Druker, BJ ;
Talpaz, M ;
Resta, DJ ;
Peng, B ;
Buchdunger, E ;
Ford, JM ;
Lydon, NB ;
Kantarjian, H ;
Capdeville, R ;
Ohno-Jones, S ;
Sawyers, CL .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) :1031-1037