Triple Negative Breast Cancer: 10-Year Survival Update of The Applied Treatment Strategy in Kuwait.

BACKGROUND: Triple negative breast cancer (TNBC) is recognized as a distinct clinical and biological entity of poor outcome for almost two decades, yet its treatment strategy still needs to be better specified. The study aim is to update the 10-year survival data of our TNBC patients and to find its association with different treatment modalities. PATIENTS AND METHODS: We updated the 10-year survival data of 359 women diagnosed with TNBC between 1999 and 2009 in the Kuwait Cancer Control Center (KCCC). The overall survival (OS), disease free survival (DFS), distant metastasis free survival (DMFS) and loco-regional recurrence free survival (LRFS) were estimated using Kaplan Meier method. Survival was correlated with different prognostic factors and treatment modalities. Statistical significance was calculated using the log-rank test and defined as p < 0.05. Cox regression is used for Multivariate analysis. RESULTS: TNBC represented 12% of breast cancer in Kuwait with a median age of 48 years. The stage distribution was as follow: stage I, II, III, IV in 15%, 43%, 35% and 7% of patients respectively. Regarding surgery, 33% had Conservative surgery; 67% had mastectomy; 82% had axillary clearance. Chemotherapy was neoadjuvant in 25%, adjuvant in 56% and palliative in 5% of patients. Two-thirds of patients (67%) received adjuvant radiotherapy. After a median follow-up of 108 months, the 10-year OS, DFS, DMFS and LRFS were 66%, 59%, 72% and 77% respectively. The 10-year OS was 92%, 80%, 49% and 0% for Stage I, II, III and IV respectively (p =< 0.0001). OS was significantly worse with the presence of lymphovascular invasion (LVI) with p = 0.003. OS was not significantly affected by age, grade or treatment modality. In multivariate analysis, the clinical stage and LVI were still significant (P<0.0001 and 0.04 respectively). CONCLUSION: In the absence of biological biomarkers, clinical stage and LVI seem to be the only significant prognostic factors for survival of TNBC patients in our study population. Timing of chemotherapy as well as the extent of surgery do not seem to affect the TNBC patients' outcome.

Polymeric and Non Polymeric Injectable In-situ Forming Implant Systems for Sustained Delivery of Lornoxicam: In vitro and In vivo Evaluation.

OBJECTIVE: Formulation of injectable In situ forming implant (ISI) systems of lornoxicam for dental and postoperative pain management to decrease dosing frequency and increase patient compliance. METHODS: Polymeric in situ implant solutions were prepared using different concentrations and inherent viscosities of Poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG) using 22X4 factorial experimental design. Nonpolymeric systems were prepared using different concentrations of lipids like cetyl alcohol and stearyl alcohol and also sucrose acetate isobutyrate (SAIB) using 32 factorial experimental design. In vitro release study, rheological measurement, syringeability assessment and effect of γ-sterilization were used for evaluation of the prepared formulae. In vivo pharmacokinetic study of lornoxicam from the most optimum formula was conducted in a rabbit model using HPLC analysis of blood samples. RESULTS: Polymeric systems showed high burst release followed by very slow release rate over 72 hours. Formula I 24 (containing SAIB 80% (w/w)) showed relatively low burst release followed by diffusion controlled release pattern, low viscosity, Newtonian flow behavior and good syringeability. γ- sterilization had no significant effect on the in vitro release and the physical nature of the most optimum formula. In vivo study concluded that intramuscularly injected In situ implant formula I 24 showed prolonged release pattern compared to the marketed product which was indicated by the increased Tmax and the extended mean residence time. CONCLUSION: Lornoxicam ISI systems could be promising as convenient injectable sustained release delivery systems for dental and postoperative pain management.

Formulation and evaluation of injectable in situ forming microparticles for sustained delivery of lornoxicam.

The objective of this study is to formulate biodegradable in situ microparticles (ISM) containing lornoxicam for post-operative and arthritic pain management. ISM emulsions were prepared according to 25 full factorial experimental design to investigate the influence of formulation variables on the release profile of the drug. The independent variables studied are the polymer type, polymer inherent viscosity, polymer concentration, oil type and polymer:oil ratio. In vitro drug release, microscopical examination, particle size determination and syringeability measurement were selected as dependent variables. The effect of γ-sterilization on the prepared formulae was also examined. The prepared formulae showed extended drug release over two weeks, and flow time below 5 s/ml. Scanning electron microscope revealed that the prepared microparticles were spherical in shape, with diameter ranging from 3.45 to 22.78 µm. In vivo pharmacokinetic evaluation of two selected optimum formulations in rabbits showed prolonged drug absorption indicated by delayed Tmax and the extended mean residence time. In conclusion, the prepared injectable ISM could be a promising approach for providing extended delivery of lornoxicam with low initial burst effect.