Bulletin du cancer
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Review Meta Analysis
[Systematic review 2007: Primary treatments of testicular germ cell tumors after radical orchydectomy].
The "Standards, Options and Recommendations" (SOR)program in oncology, has been initiated in 1993 by the Federation of French Cancer Centres and is realised in collaboration with public and private clinicians,professional federations, scientific societies and since 2005 with National cancer institute. Its aims are to develop clinical practice guidelines (CPG), health technologic assessment reports and systematic reviews. By preparing the latter, it provides support to the scientific societies for the update of their CPG. In this context, the SOR, in collaboration with the French Association of Urology (AFU), has developed a systematic review on the management of nonseminomatous (NSTGC) or seminomatous(STGC) testicular germ cell cancer treated with primary radiotherapy (RT), chemotherapy (CT) or surveillance (SV) after radical orchidectomy. Today, 80 % of patients with testicular germ cell cancer, including metastatic stage, can be cured. Actual challenges are to limit morbidity and late sequels of treatments while maintaining their therapeutic efficacy. Following this goal, surveillance, considered as a therapeutic option, is being broadly developed particularly for localised tumours. ⋯ The choice of risk-adapted treatment for patients with locally NSTGC of the testis seems to be appropriate: SV for low risk patients and CT for others. For advanced stage, the suppression of bleomycine remains questionable. For local STGC, the choice of SV or CT versus RT needs to be confirmed by RCT with prolonged follow-up according to promising results in term of toxicity obtained with carboplatine or lower irradiation dose (20 Gy instead of 30 Gy). Finally, for advanced STGC, the utility of carboplatine single agent treatment versus cisplatin-based combination chemotherapy has not been proved.
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The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. ⋯ All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.
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Approximately 90 % of gastrointestinal tumors (GISTs) harbor an activating mutation in KIT or PDGFR alpha oncogene known to confer imatinib sensitivity. Imatinib is a tyrosine kinase inhibitor of KIT and PDGFRs that yields a 6-months progression-free survival (PFS) rate of 80 % in patients with advanced GISTs. Several studies have shown that response to imatinib in GIST patients mainly depends on the mutational status of KIT or PDGFR alpha. ⋯ Sunitinib is another approved drug and an inhibitor of multiple tyrosine kinases including KIT, PDGFR alpha as well as PDGFR beta and VEGFRs which are associated with angiogenesis. Sunitinib, in phase II and III trials was associated with durable clinical benefit in nearly 25 % of patients with advanced GIST resistant/intolerant to imatinib. Clearly, a better knowledge of the molecular mechanisms underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine kinase inhibitors may allow in the near future new individualized therapeutic strategies for GISTs patients.
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Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is now an entire part of treatment of peritoneal dissemination of colorectal malignancy, and it's possible to hope prolonged survival. This treatment is more and more codified. ⋯ Last big published series results show a decrease of morbidity and mortality and interest of using new drugs like oxaliplatine. Indications have to be more homogeneous and based on evidences.
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Imatinib mesylate (Gleevec, Glivec, Novartis, Basel, Switzerland) is a small molecule inhibitor of the tyrosine kinase c-abl, c-kit and the platelet derived growth factor receptor (PDGFR). Imatinib was developed for the treatment of chronic myeloid leukaemia (CML) but was approved both in Europe and the US fro the treatment of CML and gastrointestinal stromal tumors (GIST). Given its activity against both c-kit and PDGFR kinases and its remarkable safety profile, imatinib has been 'tried' in several solid tumors; results however have often been deceiving. We review the current data regarding the activity of imatinib in solid tumors, including GIST.