الفهرس 
coverEnglishOnly 14 pages are availabe for public view
 |  | from | 170 |  |  |
| | | from | 170 | | |
Abstract
Better Understanding Of The Clinical Pharmacology Of Antineoplastic Agents Will Improve The Output Of Cancer Chemotherapy. Clinical Monitoring And Pharmacokinetic Data Offer The Possibility Of Tailoring Drug Delivery To Particular Patients Needs. Therefore, The Ultimate Goal Is Optimization Of The Dose Which Will Lead To Minimization Of Side Effects And Maximum Therapeutic Effect.<Br>Drug Concentration Measurements Are The Heart Of Drug Monitoring And Pharmacokinetic Studies. These Measurements Can Serve As A Useful Tool Which May Help In The Elucidation Of The Relationship Between Drug Concentration And Pharmacologic Or Therapeutic Effect. Cancer Patients May Have Significant Hepatic Or Renal Dysfunction And Other Abnormalities That May Lead To Alterations In The Pharmacokinetic Parameters. Appreciation Of Inter And Intrapatient Variabilities Is Potentially Of Great Importance For Optimizing Antineoplastic Therapy. Therefore, These Variabilities Should Be Carefully Considered Prior To Dosing In order To Minimize The Risk Of An Undesirable Outcome.High Dose MTX (Methotrexate) Is Included In Chemotherapy Regimens Used To Treat A Number Of Malignant Neoplasms. HD MTX Therapy With The Addition Of Leucovorin Rescue Offer The Advantage Of Minimal Bone Marrow Toxicity. However, HDMTX (Regimens) Should Be Instituted Only When Plasma Monitoring Is Available To Determine The Adequacy Of Drug Clearance And The Risk Of Serious Toxicity (Chu And Allegra, 1996).This Study Was Initiated To Comparatively Investigate The Biochemical, Pharmacokinetic (PK) And Clinical Responses Of Different Doses Of HD MTX Mainly 1 , 2 And 3 Gm/M2 Among Children (65) Treated At SECI – Assiut University During Years 2004 – 2005. The Results Were Compared With The Outcome Of Results Of (147) Patients Treated At NCI- Cairo University.The Results Obtained In The Study Revealed :1- With Respect To Age, There Is No Significant Difference Between The Two Studied Groups.2- With Respect To Sex, The Number Of Male Patients Treated At SECI And NCI Was Significantly Higher Than That Of Female.<Br>3- Patients In SECI With ALL Were Treated With 1 Gm (12.2%), 2 Gm (14.7%) And 3 Gm (73.2%) MTX Respectively, Complete Remission Was Achieved In 40%, 83.3% And 63.3%, Relapse Occur In 20%, 0% And 10% And Death Was Reported In 40%, 16.7% And 26.7%, Respectively. - Patients In NCI With ALL Were Treated With 2 Gm MTX, Complete Remission Was Achieved In 62.6% Of Them, Relapse Occur In 6.5% While 30.9% Died.<Br>4- In Both NCI And SECI, The Highest Cure Rate Was Achieved Among ALL Patients Received 2 Gm/M2 MTX, They Also Showed A Lower Percent Of Relapse And Death.5- The Results In SECI Showed That 75%, 16.7% And 8.3% Of NHL Patients Received 1 Gm, 2 Gm And 3 Gm MTX, Complete Remission Was Achieved In 38.9%, 50% And 100% Respectively, While Death Was Reported In 61.1%, 50% And 0% Respectively.- Among The NCI 20.8% And 79.2% Patients With NHL Received 2gm And 3gm MTX Respectively, Complete Remission Was Achieved In 80% And 68.4%, Relapse Occur In 20% And 15.7% And Death Was Reported In 0% And 15.8% Respectively.6- Also, The Highest Cure Rate Was Observed Among Those Received 2 Gm/M2 MTX But They Have A Higher Percent Of Relapse Than Those Received 3 Gm/M2 MTX.Dividing Patients Into 5 Years Age Intervals Revealed That The Percent Of Complete Remission Was Significantly Higher Than That Of Relapse And Death In Both Age Groups 5 Years And 5-10 Years In Both SECI And NCI. Eighteen Patients Treated With HD MTX As A Part Of Their Treatment Protocols. They Are Classified According To Their Clinical Diagnosis Into: 11 ALL Patients (5 Patients Treated With 2 Gm/M2/ 6 Hrs. And 6 Patients Treated With 3 Gm/M2/6 Hrs) And 7 NHL Patients (6 Patients Treated With 1 Gm/M2/ 6 Hrs. And 1 Patients Treated With 2 Gm/M2/ 6 Hrs.).- The Mean Serum Levels Of Creatinine And Albumin Were Within The Normal Range While The Mean Values Of Both SGOT And SGPT Were Higher Than The Average. Also, The Mean Value Of HB Was Lower Than The Normal Range While That For Wbcs, Rbcs And Plts Were Within The Normal Range.- Elevated Serum Creatinine Levels Was Observed 48 Hrs After Treatment Compared To Their Levels 48 Hours Before Treatment In Patients Treated With 1 Gm, 2 Gm And 3 Gm MTX.- This Regimen Can Be Employed Safely Only In Patients With Normal Renal And Hepatic Functions. In This Study, Determination Of PK Parameters Mainly: AUC, Css And Cl Revealed Great Inter And Intrapatient Variability Among These Pharmacokinetic Parameters Of The 3 Groups Of Patients.- AUC And Css Were Insignificantly Higher In Patients Treated With 3 Gm MTX Compared To Those Treated With 1gm And 2 Gm MTX. - On The Other Hand, Cl Was Higher In Patients Treated With 2 Gm MTX Compared To That Of 1 Gm And 3 Gm MTX. - A Strong Negative Correlation Was Found Between AUC-Css And Cl And A Significant Positive Correlation Was Detected Between The AUC-Css With MTX Dose.- Furthermore, The Rapid Clearance Of 2 Gm MTX In Comparison To 1 Gm And 3 Gm MTX Explained The Reduced Toxic Effects.