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Monday, December 20, 2010

Clinical resistance to Imatinib (Gleevec)^-www.drkeyurbhatt.in*

Unfortunately, the majority of patients treated with imatinib mesylate will develop clinical resistance to this
agent and eventual progression of disease. Much research has been focused on the predictors and potential mechanisms of the development of recurrence to targeted therapy. A review of 934 patients with advanced GISTs treated with imatinib determined that patients who developed early resistance (defined as resistance within 3 months of initiating therapy) were more likely to have lung metastases without liver metastases, low hemoglobin, and a high granulocyte count . On the other hand, prognostic factors for the development of late resistance (after 3 months of initiating therapy) were found to be a high baseline granulocyte count, large size of tumor, and nongastric primary.

Because progression eventually develops in a significant number of patients with GISTs treated with imatinib,
additional targeted inhibitors have been evaluated for the treatment of these patients. As yet, only sunitinib has been approved by the US Food and Drug Administration (FDA) for patients with imatinib-resistance or imatinib-intolerance. Sunitinib is a multitargeted agent, an inhibitor of tyrosine kinase, of KIT and PDGFRA/B and of the vascular endothelial growth factor receptors (VEGFRs)-1, -2 and 3, FMS-like tyrosine kinase-3 (FLT3), colony stimulating factor 1 receptor (CSF-1R), and glial cell-line derived neurotrophic factor receptor.

In any patient with advanced GIST who underwent targeted therapy, the treating physician should periodically reassess the potential operability, after the completion of a certain course of imatinib or other form of therapy.

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Gastrointestinal Stromal Tumors (GISTs): An Updated Experience^-www.drkeyurbhatt.in*

Review article: Dig Dis Sci (2010) 55:3315–3327

summary:

Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumors of the gastrointestinal tract. Over the last decade, GISTs have gained an extremeinterest, not only for surgeons but also for oncologists. The role of targeted therapy with tyrosine kinase inhibitors has revolutionized the care of these patients, and has made GISTs the paradigm for molecular cancer therapy. For patients with primary GISTs surgery is the treatment of choice. A combination of imatinib therapy and surgery may be effective in a subset of patients with metastatic or unresectable primary GISTs. Meanwhile, the advances in the understanding of the pathogenesis and treatment of these tumors may render feasible, in the near future, the advent of newer and more efficacious treatment options.

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Sunday, December 19, 2010

Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in JAPAN^-www.drkeyurbhatt.in*

Int J Clin Oncol (2008) 13:416–430

The Japan Society of Clinical Oncology 2008

Toshirou Nishida · Seiichi Hirota · Akio Yanagisawa
Yoshinori Sugino · Manabu Minami
Yoshitaka Yamamura · Yoshihide Otani
Yasuhiro Shimada · Fumiaki Takahashi · Tetsuro Kubota

SPECIAL ARTICLE

Clinical practice guidelines for gastrointestinal stromal tumor (GIST)
in Japan: English version

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International guidelines for GIST management^-www.drkeyurbhatt.in*

ESMO (European Society of Medical Oncologists) and NCCN (National Comprehensive Cancer Network) recommend:

1. Available data confi rm the safety and effi cacy of Imatinib mesylate at 400 mg per day as the initial standard dose to achieve response induction.
2. Data have been provided that patients with exon 9 KIT mutations fare better in terms of progression-free survival on a higher dose level i.e. 800 mg daily, which is therefore standard treatment in this subgroup.
3. Th e standard approach in the case of tumour progression is to increase the Imatinib mesylate dose to 800 mg daily. Also patient non-compliance should be ruled out as a possible cause of tumour progression, as well as drug interactions with concomitant medications.
4. Treatment should be continued indefi nitely, since treatment interruption is generally followed by relatively rapid tumour progression in virtually all cases.