ABSTRACT
BACKGROUND: The purpose of this study was to test the hypothesis that the immunohistochemical expression of ERCC1 and RASSF1A would predict both response to and survival after docetaxel and cisplatin combination chemotherapy in inoperable or recurrent head and neck squamous cell carcinoma. PATIENTS AND METHODS: A total of 54 patients were treated with frontline systemic chemotherapy composed of docetaxel (60 mg/m(2)) and cisplatin (65 mg/m(2)), every 3 weeks for up to 6 cycles. The expression levels of ERCC1 and RASSF1A were evaluated in the available 36 prechemotherapy samples. RESULTS: The overall objective response rate was 35% (complete remission 12% and partial remission 23%). The median progression-free survival and overall survival (OS) times were 5.0 months (95% confidence interval (CI), 3.7-6.4 months) and 24.2 months (95% CI, 3.5-45.0 months), respectively. The status of low ERCC1 and high RASSF1A expression was an independent favorable prognostic factor for OS in multivariate analysis (p = 0.043; hazard ratio, 7.224; 95% CI, 1.060-49.217). Toxicities were comparable with those of previously reported trials. CONCLUSIONS: Less intensive doses of cisplatin and docetaxel are active but not effective in reducing toxicity. Also, both ERCC1 and RASSF1A might be useful prognostic markers in this regimen.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/secondary , DNA-Binding Proteins/metabolism , Endonucleases/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/secondary , Neoplasm Recurrence, Local/drug therapy , Tumor Suppressor Proteins/metabolism , Carcinoma, Squamous Cell/mortality , Cisplatin/administration & dosage , Docetaxel , Female , Head and Neck Neoplasms/mortality , Humans , Incidence , Male , Neoplasm Recurrence, Local/mortality , Prognosis , Republic of Korea/epidemiology , Risk Factors , Survival Analysis , Survival Rate , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
The incidence of rheumatoid arthritis and osteoarthritis is on the rise due to our expanding elderly population. Total joint arthroplasty is the most successful, prevalent treatment modality for these and other degenerative hip conditions. Despite the wide array of prosthetic devices commercially available, hip prostheses share a common problem with a gradual and then accelerating loss of bone tissue and bone-implant interface integrity, followed by implant instability and loosening. Implant failure is largely the result of inevitable wear of the device and generation of wear debris. To provide information for the development of improved prosthetic wear characteristics, we examined the effects of size-separated titanium particles on bone forming cell populations. We demonstrate unequivocally that particle size is a critical factor in the function, proliferation, and viability of bone-forming osteoblasts in vitro. In addition, we have elucidated the time-dependent distribution of the phagocytosed particles within the osteoblast, indicating an accumulation of particles in the perinuclear area of the affected cells. The report finds that particle size is a critical factor in changes in the bone formation-related functions of osteoblasts exposed to simulate wear debris, and that 1.5-4 microm titanium particles have the greatest effect on osteoblast proliferation and viability in vitro. The size of titanium particles generated through wear of a prosthetic device may be an important consideration in the development of superior implant technology.
