Maubec E.,University Paris Diderot |
Petrow P.,Institute Curie |
Scheer-Senyarich I.,University Paris Diderot |
Duvillard P.,Institute Gustave Roussy |
And 15 more authors.
Journal of Clinical Oncology | Year: 2011
Purpose: To evaluate the efficacy and safety of cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin (SCCS). Patients and Methods: Thirty-six patients received cetuximab (initial dose of 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) for at least 6 weeks with a 48-week follow-up. The primary end point was the disease control rate (DCR) at 6 weeks (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria). Secondary end points included best response rate, overall survival, progression-free survival (PFS), and toxicity assessment. Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated. Results: Median age of the study population was 79 years. DCR at 6 weeks was obtained in 25 of 36 patients (69%; 95% CI, 52% to 84%) of the intention-to-treat population. The best responses were eight partial responses and two complete responses. There were no cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. One HRAS mutation was identified. Combined FcγRIIa-131H/H and/or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes. Conclusion: As a first-line treatment in patients with unresectable SCCS, cetuximab achieved 69% DCR. A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients. The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition. © 2011 by American Society of Clinical Oncology. Source
Rebours V.,UniversiteParis Diderot |
Vullierme M.-P.,Service de radiologie |
Hentic O.,UniversiteParis Diderot |
Maire F.,UniversiteParis Diderot |
And 3 more authors.
Pancreas | Year: 2012
OBJECTIVES: Smoking has been shown to affect the course of alcoholic chronic pancreatitis (ACP). However, a dose-dependent relationship between ACP course and the amount of tobacco consumption has not been studied. METHODS: All consecutive smokers with ACP were included prospectively. Thresholds were defined at 10, 15, 20, and 30 pack-years (p.y.) to assess the relationship between tobacco intake and ACP complications. Statistical adjustment on alcohol intake was performed. RESULTS: One hundred eight patients (male, 86%) were included. The median tobacco intake was 30 p.y. (range, 3-90 p.y.) Pancreatic calcifications and duct abnormalities were observed in 70% and 73%, respectively. Pancreatic exocrine insufficiency and diabetes mellitus were observed in 36% and 30%, respectively. No differences in ACP outcome were seen at 10-p.y. threshold. At a 15-p.y. threshold, ACP diagnosis was made earlier (36 versus 46 years; P = 0.0036). At a 20-p.y. threshold, ACP occurred earlier (P = 0.0002), and the patients had more often calcifications (P = 0.05). Similar results were observed at the 30-p.y. threshold, but additionally pancreatic exocrine insufficiency occurred earlier (P = 0.04). CONCLUSION: Tobacco intake accelerates the course of ACP in a dose-dependent fashion, apart from the amount of alcohol intake. A major threshold effect is seen in 20 p.y. Copyright © 2012 by Lippincott Williams & Wilkins. Source