title: Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib.
abstract: Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.
authors.affiliation: University Hospital Lausanne, Cancer Center, Lausanne, Switzerland. michael.montemurro@chuv.ch
authors.forename: M
authors.initials: M
authors.lastname: Montemurro
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.forename: P
authors.initials: P
authors.lastname: Reichardt
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.forename: J
authors.initials: J
authors.lastname: Schütte
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: R
authors.initials: R
authors.lastname: von Moos
authors.forename: B
authors.initials: B
authors.lastname: Seddon
authors.forename: H
authors.initials: H
authors.lastname: Joensuu
authors.forename: C M
authors.initials: CM
authors.lastname: Wendtner
authors.forename: E
authors.initials: E
authors.lastname: Weber
authors.forename: V
authors.initials: V
authors.lastname: Grünwald
authors.forename: A
authors.initials: A
authors.lastname: Roth
authors.forename: S
authors.initials: S
authors.lastname: Leyvraz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010879:Piperazines / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000077210:Sunitinib