Éditeur(s) : HAL CCSD Impact journals
Résumé : International audience
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine. We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients. Frequencies of ROS1 and RET rearrangements were 2.1% and 2.52%, respectively. Contrary to common belief, both ROS1 and RET rearrangements were detected in patients with a history of smoking, and the RET-positive patients were not younger than the negative patients. Moreover, RET but not ROS1 rearrangement was associated with the female gender. Nearly half of the ROS1-rearranged patients were successfully treated with ROS1 TKIs. In contrast, only 5/18 RET-positive patients received off-label RET TKIs. Two patients had stable disease, and three experienced disease progression. In addition to the 18 RET-positive cases, 10 showed isolated 5' signals. The clinical relevance is unknown but if the frequency is confirmed by other groups, the question whether these patients are eligible to TKIs will arise. More potent RET TKIs are under development and may improve the response rate in RET-positive patients. Therefore, we recommend the routine implementation of RET testing in non-squamous NSCLC patients, including those with a history of smoking.
ISSN: 1949-2553

hal-01578586
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578586
DOI : 10.18632/oncotarget.18408
PUBMED : 28881815

Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 μg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.
ISSN: 0163-4453

hal-00875067
https://hal.archives-ouvertes.fr/hal-00875067
DOI : 10.1016/j.jinf.2013.05.007
PUBMED : 23800784

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. CASE REPORT: A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. CONCLUSION: Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea.
Revue des Maladies Respiratoires

hal-01072996
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01072996
DOI : 10.1016/j.rmr.2013.09.001
PUBMED : 24878159

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Introduction: Hydroxyurea is an antimetabolite widely used in the treatment of myeloproliferative diseases. Usual side effects are mainly hematological, gastrointestinal, neurological disorders and induced-fevers. More rarely, hydroxyurea-induced pneumonitis are reported. Case report: We report a case of a patient treated for polycythemia vera. She was admitted 20 days after introduction of hydroxyurea for a high fever, productive cough and clear sputum associated with nausea. Chest CT-scan found diffuse bilateral ground-glass opacities. The microbiological investigations were negative. Symptoms disappeared few days after discontinuation of treatment. Its reintroduction led to recurrence of symptoms. Conclusion: This additional case completes the 15 cases of hydroxyurea-induced pneumonitis described in the literature. Two forms of this disease seem to exist: an acute form with fever occurring in the month following introduction of hydroxyurea; and a chronic form without fever. Even if it is uncommon, pulmonologists should be aware of this complication.
ISSN: 0761-8425

hal-00916333
https://hal.archives-ouvertes.fr/hal-00916333
https://hal.archives-ouvertes.fr/hal-00916333/document
https://hal.archives-ouvertes.fr/hal-00916333/file/hydroxyurA_e_version_rA_visA_e.pdf
DOI : 10.1016/j.rmr.2013.09.001

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0309-0167

hal-01118504
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118504
PUBMED : 20716175
DOI : 10.1111/j.1365-2559.2010.03605.x