Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
George D. Demetri,Margaret von Mehren,Charles D. Blanke,Annick D. Van den Abbeele,Burton L. Eisenberg,Peter J. Roberts,Michael Heinrich,David A. Tuveson,Samuel Singer,Milos J. Janicek,Jonathan A. Fletcher,Stuart G. Silverman,Sandra Silberman,Renaud Capdeville,Beate Kiese,Bin Peng,Sasa Dimitrijevic,Brian J. Druker,Christopher L. Corless,Christopher D.M. Fletcher,Heikki Joensuu +20 more
Reads0
Chats0
TLDR
Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, indicating that inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinalStromal tumors, which resist conventional chemotherapy.Abstract:
Background Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors. Methods We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed antitumor response and the safety and tolerability of the drug. Pharmacokinetics were assessed in a subgroup of patients. Results A total of 147 patients were randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79 patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had stable disease, and for technical reasons, response could not be evaluated in 7 patients (4.8 percent). No patient had a complete response to the treatment. The median duration of response had not been reached after a median follow...read more
Figures
Figure 2. Sequential PET Scans Obtained in the Same Patient at Base Line (before Treatment, Panel A), 1 Month after Imatinib Treatment Began (Panel B), and after 16 Months of Continuous Treatment (Panel C). 
TABLE 3. ADVERSE EFFECTS WITH A POSSIBLE OR SUSPECTED RELATION TO IMATINIB.* 
Figure 3. Biopsy Specimens of Metastatic Malignant Gastrointestinal Stromal Tumors before Treatment and after Four Weeks of Daily Treatment with Imatinib. 
Figure 1. Kaplan–Meier Estimates of Overall Survival and Time to Treatment Failure for All Patients. Each arrowhead represents the point at which a patient’s data were censored.
Citations
More filters
Journal ArticleDOI
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
J. Guillermo Paez,Pasi A. Jänne,Pasi A. Jänne,Jeffrey C. Lee,Sean Tracy,Heidi Greulich,Heidi Greulich,Stacey Gabriel,Paula Herman,Frederic J. Kaye,Neal I. Lindeman,Titus J. Boggon,Katsuhiko Naoki,Hidefumini Sasaki,Yoshitaka Fujii,Michael J. Eck,William R. Sellers,William R. Sellers,William R. Sellers,Bruce E. Johnson,Bruce E. Johnson,Matthew Meyerson,Matthew Meyerson +22 more
TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.
Journal ArticleDOI
Photodynamic therapy for cancer
TL;DR: PDT is being tested in the clinic for use in oncology — to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin.
Journal ArticleDOI
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Jeffrey A. Engelman,Kreshnik Zejnullahu,Tetsuya Mitsudomi,Youngchul Song,Courtney Hyland,Joon Oh Park,Neal I. Lindeman,Christopher-Michael Gale,Xiaojun Zhao,James J. Christensen,Takayuki Kosaka,Alison J. Holmes,Andrew M. Rogers,Federico Cappuzzo,Tony Mok,Charles Lee,Bruce E. Johnson,Lewis C. Cantley,Pasi A. Jänne +18 more
TL;DR: It is proposed that MET amplification may promote drug resistance in other ERBB-driven cancers as well after it was found that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)–dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors.
Journal ArticleDOI
Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.
Ross L. Levine,Ross L. Levine,Martha Wadleigh,Jan Cools,Benjamin L. Ebert,Benjamin L. Ebert,Gerlinde Wernig,Brian J. P. Huntly,Titus J. Boggon,Iwona Wlodarska,Jennifer J. Clark,Sandra A. Moore,Jennifer Adelsperger,Sumin Koo,Jeffrey C. Lee,Stacey Gabriel,Thomas Mercher,Alan D. D'Andrea,Stefan Fröhling,Konstanze Döhner,Peter Marynen,Peter Vandenberghe,Ruben A. Mesa,Ayalew Tefferi,James D. Griffin,Michael J. Eck,William R. Sellers,William R. Sellers,Matthew Meyerson,Matthew Meyerson,Todd R. Golub,Todd R. Golub,Todd R. Golub,Stephanie J. Lee,D. Gary Gilliland,D. Gary Gilliland,D. Gary Gilliland +36 more
TL;DR: High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations.
Journal ArticleDOI
Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations
Keith T. Flaherty,J. R. Infante,Adil Daud,Rene Gonzalez,Richard F. Kefford,Jeffrey A. Sosman,Omid Hamid,Lynn M. Schuchter,Jonathan Cebon,Nageatte Ibrahim,Ragini Kudchadkar,Howard A. Burris,Gerald S. Falchook,Alain Algazi,Karl D. Lewis,Georgina V. Long,Igor Puzanov,Peter F. Lebowitz,Ajay Singh,Shonda M Little,Peng Sun,Alicia Allred,Daniele Ouellet,Kevin B. Kim,Kiran Patel,Jeffrey S. Weber +25 more
TL;DR: Dabrafenib and trametinib were safely combined at full monotherapy doses, and the rate of pyrexia was increased with combination therapy, whereas the rates of proliferative skin lesions was nonsignificantly reduced.
References
More filters
Journal ArticleDOI
Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia
Brian J. Druker,Moshe Talpaz,Debra Resta,Bin Peng,Elisabeth Buchdunger,John Ford,Nicholas B. Lydon,Hagop M. Kantarjian,Renaud Capdeville,Sayuri Ohno-Jones,Charles L. Sawyers +10 more
TL;DR: STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
Journal ArticleDOI
Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.
Brian J. Druker,Shu Tamura,Elisabeth Buchdunger,Sayuri Ohno,Gerald M. Segal,Shane Fanning,Jürg Zimmermann,Nicholas B. Lydon +7 more
TL;DR: A compound, designed to inhibit the Abl protein tyrosine kinase, was evaluated for its effects on cells containing the Bcr–Abl fusion protein and it was found that this compound may be useful in the treatment of bcr–abl–positive leukemias.
Journal ArticleDOI
Diagnosis of gastrointestinal stromal tumors: A consensus approach.
Christopher D.M. Fletcher,Jules J. Berman,Christopher L. Corless,Fred Gorstein,Jerzy Lasota,B. Jack Longley,Markku Miettinen,Timothy J. O'Leary,Helen Remotti,Brian P. Rubin,Barry M. Shmookler,Leslie H. Sobin,Sharon W. Weiss +12 more
TL;DR: Key elements of the consensus are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time.
Journal ArticleDOI
Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification
Mercedes E. Gorre,Mansoor Mohammed,Katharine Ellwood,Nicholas C. Hsu,Ron Paquette,P. Nagesh Rao,Charles L. Sawyers +6 more
TL;DR: It is found that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined and a strategy for identifying inhibitors of STI-571 resistance is suggested.
Journal ArticleDOI
Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome
Brian J. Druker,Charles L. Sawyers,Hagop M. Kantarjian,Debra Resta,Sofia Fernandes Reese,John Ford,Renaud Capdeville,Moshe Talpaz +7 more
TL;DR: The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL.
Related Papers (5)
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Michael Heinrich,Christopher L. Corless,George D. Demetri,Charles D. Blanke,Margaret von Mehren,Heikki Joensuu,Laura McGreevey,Chang Jie Chen,Annick D. Van den Abbeele,Brian J. Druker,Beate Kiese,Burton L. Eisenberg,Peter J. Roberts,Samuel Singer,Christopher D.M. Fletcher,Sandra Silberman,Sasa Dimitrijevic,Jonathan A. Fletcher +17 more