Quelle place pour les traitements médicaux avant et après chirurgie es stades localisés ?

ONCOLOGIE ◽  
2018 ◽  
Vol 20 (7-12) ◽  
pp. 204-210
Author(s):  
V. Cochin ◽  
M. Gross-Goupil ◽  
A. Ravaud
Keyword(s):  
Tyrosine Kinase ◽  
Phase Iii ◽  
Recherche Clinique ◽  
Cancer Du Rein ◽  
Néphrectomie Partielle ◽  
Inhibiteurs De Tyrosine Kinase ◽  
Traitements Médicaux

La place des traitements médicaux adjuvants dans les stades localisés du cancer du rein reste en France du domaine de la recherche clinique en 2017. Seul l’essai S-TRAC évaluant un an de sunitinib versus placebo a montré une augmentation significative de la survie sans maladie de 5,6 à 6,8 ans (HR = 0,76 ; p = 0,03) contrairement aux deux essais publiés de phase III, ASSURE (sunitinib ou sorafénib versus placebo un an) et PROTECT (pazopanib versus placebo un an). De nombreux essais d’immunothérapie avec les inhibiteurs des points de contrôle de la réponse immunitaire sont en cours. Les inhibiteurs de tyrosine-kinase ont démontré une efficacité en néoadjuvant en termes de réponse tumorale (de 18 à 28 %) sans toxicité surajoutée lors de la chirurgie et permettant le plus souvent une épargne néphronique. Néanmoins, cette stratégie versus une néphrectomie partielle d’emblée dans une équipe entraînée n’a pas été démontrée.

scholarly journals Canadian perspectives: update on inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
B. Melosky ◽  
P. Cheema ◽  
J. Agulnik ◽  
R. Albadine ◽  
D. G. Bebb ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Alk Inhibitor ◽  
Alk Positive

BackgroundInhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update.MethodsClinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK-positive nsclc.ResultsRandomized phase iii trials have demonstrated clinical benefit for single-agent alectinib and ceritinib used in treatment-naïve patients and as second-line therapy after crizotinib. Phase ii trials have demonstrated activity for single-agent brigatinib and lorlatinib in further lines of therapy. Improved responses in brain metastases were observed for all second- and next/third-generation alk tyrosine kinase inhibitors in patients progressing on crizotinib. Canadian recommendations are therefore revised as follows:Patients with advanced nonsquamous nsclc have to be tested for the presence of an ALKrearrangement.Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially.Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially.Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially.Patients progressing on alk tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy.Other systemic therapies should be exhausted before immunotherapy is considered.SummaryMultiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALKrearrangement.

Une innovation thérapeutique : les inhibiteurs de tyrosine kinase de deuxième génération (ITK 2) dans le traitement de la LMC

2011 ◽  
Vol 98 (8) ◽  
pp. 859-866 ◽  
Author(s):  
Marine Demarquet ◽  
Hélène Labussière-Wallet ◽  
Emmanuelle Nicolas-Virelizier ◽  
Franck-Emmanuel Nicolini
Keyword(s):  
Tyrosine Kinase ◽  
Inhibiteurs De Tyrosine Kinase

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

2020 ◽  
Vol 38 (2) ◽  
pp. 124-136 ◽  
Author(s):  
Vanita Noronha ◽  
Vijay Maruti Patil ◽  
Amit Joshi ◽  
Nandini Menon ◽  
Anuradha Chougule ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Palliative Therapy ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
A Performance

PURPOSE Standard first-line therapy for EGFR-mutant advanced non–small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)–directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes. PATIENTS AND METHODS This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity. RESULTS Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively ( P = .01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P < .001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P < .001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively ( P < .001). CONCLUSION Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.

Targeted Therapy in Combination with Chemotherapy in Recurrent and/or Metastatic Head and Neck Cancer

2010 ◽  
Vol 06 (01) ◽  
pp. 43
Author(s):  
Pol Specenier ◽  
Jan B Vermorken ◽  
◽  
Keyword(s):  
Monoclonal Antibodies ◽  
Tyrosine Kinase ◽  
Head And Neck ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Pathway Inhibition

Two epidermal growth factor receptor (EGFR)-targeting strategies are used in recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN): monoclonal antibodies and small-molecule tyrosine kinase inhibitors. Thus far, the monoclonal antibody cetuximab has been studied in most detail. Based on the results of two randomised phase III trials, cetuximab in combination with platinum-based chemotherapy should be considered the new standard first-line regimen for patients with recurrent and/or metastatic disease for whom a platinum-based regimen regimen is considered the best treatment option. Other EGFR-directed monoclonal antibodies are under investigation. The role of EGFR tyrosine kinase inhibitors (TKIs) in SCCHN is less well established and early data on other targeted agents have also been disappointing thus far. Dual pathway inhibition may overcome resistance to single pathway inhibition.

Phase II evaluation of cisplatin plus cetuximab in the treatment of recurrent and persistent cancers of the cervix: A limited access phase II study of the Gynecologic Oncology Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5521-5521
Author(s):  
J. H. Farley ◽  
M. Sill ◽  
J. L. Walker ◽  
R. J. Schilder ◽  
J. T. Thigpen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Gynecologic Oncology ◽  
Antibody Therapy ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Poor Prognostic Factor

5521 Background: A majority of cervical cancer patients overexpress epidermal growth factor receptor (EGFR), which is a poor prognostic factor. Cetuximab (C225) is a murine monoclonal antibody that binds to EGFR and competes with ligand binding and tyrosine kinase activation.Given the evidence of activity in squamous carcinomas of the head and neck, the purpose of this study was to evaluate the safety and efficacy of cisplatin and cetuximab chemotherapy. Methods: Women with advanced, persistent, or recurrent carcinoma of the cervix not amenable to cure were eligible for this study. Only prior chemotherapy (CT) administered in conjunction with primary radiation as a radiosensitizer was allowed. Women could not have received prior anti-EGFR antibody therapy or therapy with a tyrosine kinase inhibitor that targets the EGFR pathway. All women had measurable disease and a GOG performance status ≤ 2. The women received cisplatin at 30 mg/m2 days 1 and 8. The first dose of C225 was given at 400 mg/m2. All subsequent doses of C225 were given at 250 mg/m2. C225 was given on days 1, 8, and 15. Each cycle was 21 days. Adverse events were assessed with CTCAE v 3.0. Primary measure of clinical efficacy was the frequency of tumor response. The study was stratified by prior CT. The design required at least 16 responses in a sample of 40 with prior CT and 29 without prior CT before the regimen was considered for phase III testing. Results: Between September 2004 and March 2008, 76 patients were entered onto the study. Of these, 69 were eligible and evaluable. Three patients were on study at the time of the analysis. 56 (81%) patients had received prior radiation. 40 (58%) patients previously received prior CT. There were 8 (12%) responses. The response rate was 8% among patients with prior CT, and 17% among CT naïve patients. One woman had grade 4 anemia. The most common grade 3 toxicities were metabolic (14), dermatologic (8), fatigue (6), and gastrointestinal (6). Conclusions: The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy. Stratification of patients based upon K-ras mutation and/or EGFR status may select a group for which this regimen is most effective. No significant financial relationships to disclose.

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