Objectives: Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC.
Materials And Methods: This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS).
Results: From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43-86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2-not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%-100%). The objective response rate was 81.8% (95% CI, 81.3%-98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death.
Conclusions: Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.
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http://dx.doi.org/10.1016/j.lungcan.2019.03.030 | DOI Listing |
J Gastrointest Cancer
December 2024
Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, 518100, China.
Background And Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in treatment, metastatic colorectal cancer (mCRC) remains a significant challenge due to its heterogeneity and resistance to therapy. Regorafenib, a multikinase inhibitor, can inhibit tumor progression through multiple mechanisms, thereby improving patient prognosis.
View Article and Find Full Text PDFIntroduction Parenteral heparin is widely used as bridging therapy while optimising oral anticoagulation(OAC). Newer Direct-Acting OACs(DOACs) attain therapeutic effect very quickly. We report the use of dabigatran as bridging therapy during warfarin optimization for cardioembolic stroke in two patients who opted to receive warfarin for long-term anticoagulation for secondary stroke prevention.
View Article and Find Full Text PDFInt J Drug Policy
December 2024
School of Sociology, Philosophy and Anthropology, University of Exeter, UK. FF16, Byrne House, Streatham Drive, Exeter, EX4 4AP, UK. Electronic address:
Background: Existing research highlights an increase in psychedelic microdosing, particularly for therapeutic purposes and as a means for self-enhancement. However, we know little about the different routes into and out of microdosing, particularly by those who do not consume other illicit substances, and of the processes involved in the development, maintenance, and cessation of practices.
Methods: Drawing upon a trans-national interview-based study of 23 participants actively microdosing (n = 19), about to start (n = 3), or who were past users (n = 1), we develop a phased-based analysis of different user pathways.
Clin Genitourin Cancer
October 2024
Division of Hematology-Oncology, Department of Medicine, University of California San Diego. La Jolla, CA. Electronic address:
Background: Real-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population.
Methods: In the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018.
J Assist Reprod Genet
December 2024
Service de Médecine de la Reproduction et Préservation de la Fertilité, Hôpital Antoine Béclère, Université Paris-Saclay, Assistance Publique Hôpitaux de Paris, F-92140, Clamart, France.
Purpose: To evaluate ovarian stimulation response in couples undergoing preimplantation genetic testing (PGT-M) for myotonic dystrophy type 1 (DM1) METHODS: Retrospective, observational, multicentric study. Parameters of ovarian response and PGT-M outcomes were compared according to the DM1-affected patient (female or male). A total of 229 couples underwent at least one controlled ovarian hyperstimulation cycle for the PGT-M procedure.
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