A series of new (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography—tandem mass spectrometry (UHPLC—MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (...

Introduction/Objective: The efficacy and safety of bevacizumab (BEV) in combination with capecitabin and irinotecan in first-line therapy of patients with metastatic colorectal cancer (mCRC) were studied. In order to improve safety and efficacy of chemotherapy, as well as to reduce adverse reactions to a minimum, doses of active agents applied were changed in relation to previously employed schedules. Methods: Patients with histologically documented mCRC who have not previously received chemotherapy or had received adjuvant or neoadjuvant chemotherapy, which ended 6 months before capecitabin treatment (1000 mg/m2 per os from 2nd to 8th day of each cycle), irinotecan (175 mg/m2 every 2 weeks), plus bevacizumab (5 mg/kg i.v. every 2 weeks) were observed. Results: The study, conducted as a prospective one included 35 patients of both sexes. Overall response rate (ORR) of 28.6%, partial response (PR) of 28.6%, progressive disease (PD) of 28.6% and stable disease (SD) of 42.8% were found. Progression-free survival (PFS) of the patients analyzed was 11.3 months (95% CL: 9.1 - 12.9) while overall survival (OS) of the patients included was 25.2 months (95% CL: 17.4 - 28.4 months) and 117 adverse effects were recorded in 24 patients. Alopecia, nausea and vomiting, hemorrhage, hand-foot syndrome, diarrhea, abdominal pain, proteinuria, and hypertension (51.4%, 37.1%, 37.1%, 25.7%, 22.8%, 20.0%, 20.0% and 17.1%, respectively) were most frequently observed adverse effects. Conclusion(s): The results of this clinical trial support and recommend the use of bevacizumab plus capecitabin and irinotecan in the doses and schedule applied throughout this study as first-line treatment of mCRC patients.

Introduction/Objective: The efficacy and safety of bevacizumab (BEV) in combination with capecitabin and irinotecan in first-line therapy of patients with metastatic colorectal cancer (mCRC) were studied. In order to improve safety and efficacy of chemotherapy, as well as to reduce adverse reactions to a minimum, doses of active agents applied were changed in relation to previously employed schedules. Methods: Patients with histologically documented mCRC who have not previously received chemotherapy or had received adjuvant or neoadjuvant chemotherapy, which ended 6 months before capecitabin treatment (1000 mg/m2 per os from 2nd to 8th day of each cycle), irinotecan (175 mg/m2 every 2 weeks), plus bevacizumab (5 mg/kg i.v. every 2 weeks) were observed. Results: The study, conducted as a prospective one included 35 patients of both sexes. Overall response rate (ORR) of 28.6%, partial response (PR) of 28.6%, progressive disease (PD) of 28.6% and stable disease (SD) of 42.8% were found. Progression-free survival (PFS) of the patients analyzed was 11.3 months (95% CL: 9.1 - 12.9) while overall survival (OS) of the patients included was 25.2 months (95% CL: 17.4 - 28.4 months) and 117 adverse effects were recorded in 24 patients. Alopecia, nausea and vomiting, hemorrhage, hand-foot syndrome, diarrhea, abdominal pain, proteinuria, and hypertension (51.4%, 37.1%, 37.1%, 25.7%, 22.8%, 20.0%, 20.0% and 17.1%, respectively) were most frequently observed adverse effects. Conclusion(s): The results of this clinical trial support and recommend the use of bevacizumab plus capecitabin and irinotecan in the doses and schedule applied throughout this study as first-line treatment of mCRC patients.

Nimesulide belongs to the group of semi-selective COX-2 inhibitors, widely used in solid oral formulations. In the present work the influence of surfactants among other drug excipients, as well as particle size of the active substance and the effects of medium pH on the dissolution rate of nimesulide from solid pharmaceutical forms. For that purpose, four different preparations containing 100 mg nimesulide per tablet and available in the market of Bosnia and Herzegovina (labeled here as A, B, C and D) were studied. The test for the assessment of dissolution profiles of the formulations was performed in surfactant-free dissolution medium pH 7.5. The dissolution profiles were compared by calculating difference (f1), and similarity (f2) factors. The increasing dissolution medium pH value from 7.5 to 7.75 resulted in a significant increase of nimesulide dissolution rate from the examined formulations. Also, the results showed that particle size affects to a great extent the dissolution rate and the best results were achieved with micronized nimesulide. The presence of the surfactants among the other excipients expressed a negligible effect on the dissolution profile.