Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial

@article{Verweij2004ProgressionfreeSI,
  title={Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial},
  author={Jaap Verweij and Paolo Giovanni Casali and John R. Zalcberg and Axel Lecesne and Peter Reichardt and Jean Yves Blay and Rolf D. Issels and Allan T. van Oosterom and Pancras C. W. Hogendoorn and Martine van Glabbeke and Rossella Bertulli and Ian Judson},
  journal={The Lancet},
  year={2004},
  volume={364},
  pages={1127-1134}
}
BACKGROUND Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. METHODS 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. FINDINGS At… 
Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients.
TLDR
Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit, while further dose escalation in 14 cases was ineffective, with disease progression and severe adverse events.
Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg.
TLDR
It is concluded that a cross-over to high-dose imatinib is feasible and safe in GIST patients who progress on low-dose therapy.
One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial.
TLDR
Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo and overall survival of GIST patients with a high risk of Gist recurrence.
Systemic treatment of patients with gastrointestinal stromal tumor: Current status and future opportunities
TLDR
In the setting of unresectable and metastatic GIST, long-term follow-up of the B2222 study showed that imatinib 400 and 600 mg/d produced objective responses in 68% of patients and clinical benefit in 84%; it also extended median survival from 19 months in historical controls to 57 months.
KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours.
TLDR
It is concluded that tumour genotype is of major prognostic significance for progression-free survival and overall survival in patients treated with imatinib for advanced GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug.
Clinical outcomes of imatinib dose escalation versus sunitinib in first-line imatinib-failure gastrointestinal stromal tumour
TLDR
Both imatinib dose escalation and sunitinib were optional in Asian patients after failure of first-lineImatinib-failure Asian GIST patients, and patients with KIT exon 11 mutation benefited more from a direct shift to sunit inib.
Prognosis, imatinib dose, and benefit of sunitinib in GIST: knowing the genotype.
  • I. Judson
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2008
TLDR
Patients treated with imatinib 800 mg had a superior progression-free survival (PFS) than those with wild-type disease, who had an increased risk of progression of 108% and a relative risk of death of 76% and two phase III trials were performed that compared the standard 400-mg dose with the 800-mg MTD.
Imatinib: a review of its use in the management of gastrointestinal stromal tumours.
TLDR
Imatinib dosages higher than 400 mg/day may improve progression-free survival, with an increase in dosage benefiting some patients who show disease progression at the lower dosage, particularly in those with exon 9 mutation; however, there is also a dose-related increase in imatinib toxicity.
Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib
TLDR
Dasatinib may have activity in a subset of patients with imatinib-resistant GISTs, and further study is needed to determine whether pSRC is a prognostic biomarker.
Activity and side effects of imatinib in patients with gastrointestinal stromal tumors: data from a german multicenter trial
TLDR
Imatinib 400 mg/d led to disease stabilisation in 81,6% of patients with unresectable or metastatic malignant GIST and the safety profile of imatinib based on adverse event assessment is favorable.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 38 REFERENCES
Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study
TLDR
Impatinib at a dose of 400 mg twice daily is well tolerated during the first 8 weeks, side-effects diminish with continuing treatment, and it has significant activity in patients with advanced GISTs.
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
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.
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.
  • J. Zalcberg, J. Verweij, +7 authors I. Judson
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2004
TLDR
Cross-over to HD Imatinib is feasible in most GIST pts who progress on LD therapy, despite increased fatigue and anemia, dose reduction is only required in 31% of pts within a year.
Dose effect of imatinib (IM) in patients (pts) with metastatic GIST - Phase III Sarcoma Group Study S0033.
TLDR
This multicenter study continues to demonstrate no significant differences between these two dose levels of IM while supporting the durable survival benefits of this agent in pts with metastatic GIST.
Continuous vs intermittent imatinib treatment in advanced GIST after one year: A prospective randomized phase III trial of the French Sarcoma Group
TLDR
A prospective multicentric phase III study of continuous vs interrupted imatinib treatment in advanced GIST, finding that intermittent administration of Im may prevent the long term emergence of resistant clones is unknown.
18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec).
TLDR
It is concluded that FDG-PET is an early and sensitive method to evaluate an early response to imatinib treatment and is associated with a longer progression-free survival (PFS) than conventional tomography.
Management of malignant gastrointestinal stromal tumours.
TLDR
Imatinib mesylate is the first effective systemic therapy for advanced GISTs and an orally administered selective inhibitor of certain tyrosine kinases including KIT, an early tumour-promoting event in pathogenesis.
Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review.
TLDR
Data on the prognosis of gastrointestinal stromal tumors is reviewed and genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential.
Gastrointestinal stromal tumors–a review
TLDR
Most GISTs respond to imatinib mesylate, which selectively inhibits both KIT and PDGFRA, and is now considered as the standard systemic therapy for advanced GIST.
Diagnosis of gastrointestinal stromal tumors: A consensus approach.
TLDR
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.
...
1
2
3
4
...