ABSTRACT
BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT). MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m2 in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles. RESULTS: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL. CONCLUSION: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Podophyllotoxin/analogs & derivatives , Taxoids/therapeutic use , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Chemotherapy, Adjuvant , Disease Progression , Docetaxel , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Podophyllotoxin/therapeutic use , Receptor, IGF Type 1 , Receptors, Somatomedin/antagonists & inhibitors , Receptors, Somatomedin/metabolism , Signal Transduction/drug effects , Survival Analysis , Treatment OutcomeABSTRACT
INTRODUCTION: Prevalence of post-stroke depression ranges from 20% to 50%. Treatment of depression positively correlated with the success of rehabilitation, quality of life, and the post-stroke patient's independence. AIM: The primary goal of the study was to establish the therapeutic efficacy of paroxetine (measured by the changes of Hamilton Depression Scale Score) in post-stroke depression. Secondary outcomes were changes in clinical status (based on Clinical Global Impression), alterations of mental capabilities (by Mini-Mental State Examination) and changes in quality of life (based on Quality of Life values). METHOD: An estimation of the efficacy of paroxetine treatment of 788 patients with post-stroke depression (Hamilton Depression Scale Score > 18) was performed in an open-label phase IV multicenter trial, during a clinical (8 weeks) as well as a follow-up period (a total of 26 weeks). The applied doses of paroxetine were: 20, 30 or 40 mg per day, subject to their therapeutic effect. RESULTS: On the third week of the study (i.e.: at the 2nd visit) the mean Hamilton Depression Scale Score decreased significantly to 12.3 points; from a starting mean basic score of 24.8 points. At the conclusion of the clinical phase (by the end of the 8th week) we found an Hamilton Depression Scale Score of 8.6 points, which decreased further to 6.6 points by the end of the follow-up period (i.e.: the 26th week). At the end of the 3rd week 92% of the patients stated that paroxetine was effective while this number grew to 93.1% by the end the 8th week. Events related to secondary outcomes also showed significant improvements of similar size: by the end of the 8th week the clinical status of 92.8% of the patients improved (in 81.3% by a remarkable rate); mental output of the patients (based on Mini-Mental State Examination) grew significantly from a starting score of 26.7 to 27.9 and their Quality of Life values grew from 204 points to 238 points by the end of the 8th week and by the end of the 26th week it reached to 251 points; another indication of a significant improvement of their quality of life. In the course of the study 8.21% of the patients experienced side effects; the most frequent of these were: nausea/vomiting, dizziness, headaches and diarrhea. Serious adverse events occurred in 1.9% of the patients during the 26 weeks period of the study although these were unrelated to the taking of paroxetine. In the course of the study the patients' compliance was clearly good: by the end of the 8th week 94%, at the end of the 26th week 90.7% of them reported for control visitation, in other words, during the 6 months study their dropout rate was less than 10%. CONCLUSION: the selective serotonin-reuptake inhibitor paroxetine effectively improved the symptoms of depression, the functional and cognitive performance, as well as the quality of life of patients with post-stroke depression. The drug was safe and well tolerable.
