Outcome of patients with advanced gastro-intestinal stromal tumors (GIST) crossing over to a daily imatinib dose of 800mg (HD) after progression on 400mg (LD) - an international, intergroup study of the EORTC, ISG and AGITG

Zalcberg, John; Verweij, Jaap; Casali, Paolo; Cesne, A. Le; Reichardt, Peter; Blay, Jean‐Yves; Issels, R. D.; Glabbeke, M. van; Evrard, V.; Judson, I.

doi:10.1200/jco.2004.22.14_suppl.9004

Cited by 10 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in a small group of 68 crossover patients, five patients (7%) demonstrated a partial tumor response, and 20 patients (29%) achieved stable disease with dose escalation to 800 mg/d [27]. Similar findings of improved time to progression on primary treatment with a higher dose or after crossover from 400 mg to 800 mg were also seen in the larger EORTC-ISG-AGITG study [28]. Verweij et al [29•] studied 946 GISTs and reported, at a median follow-up of 760 days, that an imatinib dose of 400 mg twice a day achieves significantly longer progression-free survival.…”

Section: Appropriate Imatinib Dosingsupporting

confidence: 71%

Imatinib resistance in gastrointestinal stromal tumors

et al. 2005

View full text Add to dashboard Cite

Conventional chemotherapeutic drugs are ineffective in treatment of gastrointestinal stromal tumors (GISTs). Imatinib (STI571, Gleevec, Glivec; Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL, BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy and has revolutionized the treatment of patients with chronic myelogenous leukemia and GISTs. Unfortunately, imatinib resistance has emerged. The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala. The established mechanisms and potential mechanisms of imatinib resistance in GISTs, the imaging studies indicative of early development of imatinib resistance, and the management of imatinib-resistant GISTs are discussed.

show abstract

Section: Appropriate Imatinib Dosingsupporting

confidence: 71%

Imatinib resistance in gastrointestinal stromal tumors

et al. 2005

View full text Add to dashboard Cite

show abstract

“…12,13 However, more prolonged TTP was shown in a limited number of patients with complete resection (Fig. 1B).…”

Section: Discussionmentioning

confidence: 93%

“…10,11 An increase in the imatinib dose (400 to 800 mg/day) was shown to have been effective for 30% of patients (PR, 2.3% and SD, 27.1%), with a median progression-free survival of 81 days and moderate safety. 12 In our series, only three patients had increased to 600 or 800 mg/day, because doses over 400 mg are not approved in Japan. Although the resistant lesions in these patients had been controlled for a few months by the dose increase, in one patient (patient 14), the progressive lesion became a huge mass, and in the other two patients (patients 15 and 16) the number of resistant lesions had increased at surgery, which might result in an incomplete resection in these patients.…”

Section: Discussionmentioning

confidence: 96%

Surgical interventions for focal progression of advanced gastrointestinal stromal tumors during imatinib therapy

et al. 2007

View full text Add to dashboard Cite

show abstract

“…These were:EORTC-ISG-AGITG (62005) trial, as reported by Zalcberg and colleagues [17] and Debiec-Rychter and colleagues [24], with one additional abstract reporting interim data [36]. …”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Escalated Imatinib Doses Compared with Sunitinib or Best Supportive Care, for the Treatment of People with Unresectable/Metastatic Gastrointestinal Stromal Tumours Whose Disease has Progressed on the Standard Imatinib Dose

Hislop

Mowatt

Sharma

et al. 2011

J Gastrointest Canc

View full text Add to dashboard Cite

IntroductionWe conducted a systematic review of evidence on the effectiveness of imatinib at escalated doses of 600 mg/day or 800 mg/day for treatment of adults with unresectable or metastatic gastrointestinal stromal tumours (GIST), following progression on imatinib at the 400 mg/day dose, compared with sunitinib and/or ‘best supportive care’.MethodsElectronic searches were undertaken to identify relevant randomised controlled trials (RCTs), non-randomised studies, and case series reporting outcome data on survival, quality of life or adverse events. Titles and abstracts were screened by two reviewers and full text reports of potentially relevant studies assessed for inclusion. Included studies were quality assessed by two reviewers and data were extracted. Five studies reported data on the relevant population and were included.Results and DiscussionMedian overall survival for imatinib (800 mg/day) and sunitinib both were less than 2 years. Around 25% of patients required either an imatinib dose delay or reduction. Approximately one-third of patients receiving dose escalated imatinib (either dose) showed either response or stable disease. Amongst those responding to the escalated 800 mg/day dose, median progression-free survival was over 25 months. The statistical likelihood of response may depend on exon mutational status. There were few data and those that were available were potentially biased, due to their non-randomised nature. Further data are needed to justify international guideline recommendations on imatinib dose escalation.ConclusionA prospective audit of management and outcomes for unresectable GIST patients treated with dose escalation upon progression at 400 mg/day may be appropriate as an RCT may be unfeasible.

show abstract

Outcome of patients with advanced gastro-intestinal stromal tumors (GIST) crossing over to a daily imatinib dose of 800mg (HD) after progression on 400mg (LD) - an international, intergroup study of the EORTC, ISG and AGITG

Cited by 10 publications

References 0 publications

Imatinib resistance in gastrointestinal stromal tumors

Imatinib resistance in gastrointestinal stromal tumors

Surgical interventions for focal progression of advanced gastrointestinal stromal tumors during imatinib therapy

Systematic Review of Escalated Imatinib Doses Compared with Sunitinib or Best Supportive Care, for the Treatment of People with Unresectable/Metastatic Gastrointestinal Stromal Tumours Whose Disease has Progressed on the Standard Imatinib Dose

Contact Info

Product

Resources

About