Method of Optimizing the treatment of Proliferative Diseases Mediated by the Tyrosine Kinase Receptor KIT with Imatinib

Abstract

The invention relates to a method of treating proliferative diseases mediated by the tyrosine kinase receptor KIT, in particular GIST, in a human patient population.

1 . A method of selectively treating a patient having GIST comprising:
 (a) administering a predetermined fixed dose of 400 mg or 600 mg of imatinib mesylate to the patient;   (b) assaying at least one blood sample from the patient within the first 12 months of treatment for a plasma trough level (Cmin) of Imatinib mesylate;   (c) thereafter, selecting the patient for adjusting the dose of imatinib mesylate on the basis of the plasma trough level (Cmin) of less than about 1100 ng/mL in the patient; and   (d) thereafter selectively adjusting the dose of Imatinib mesylate in a manner that a Cmin of between 1100 and 2500 ng/mL of Imatinib mesylate is achieved in the patient.   
     
     
         2 . The method according to  claim 1  wherein the at least one blood sample is collected within the first 3 months of treatment. 
     
     
         3 . The method according to  claim 1  wherein the at least one blood sample is collected within the first 30 days of treatment. 
     
     
         4 . The method according to  claim 1  wherein the patient is a GIST patient with the Exon 11 KIT mutation. 
     
     
         5 . A method of predicting the likelihood that a patient having GIST being treated with imatinib mesylate has an increased risk of lower overall objective response or a shorter time to progression and requires an adjustment of dose, comprising
 (a) administering a predetermined fixed dose of 400 mg or 600 mg of imatinib mesylate to the patient;   (b) assaying a blood sample within the first 12 months of treatment from the patient for the presence of a plasma trough level (Cmin) of imatinib mesylate of less than about 1100 ng/mL in the patient, wherein the presence of a plasma trough level (Cmin) of imatinib mesylate of less than about 1100 ng/mL is indicative that the patient has an increased risk of lower overall objective response or a shorter time to progression;   (c) thereafter, selecting the patient for adjusting the dose of imatinib mesylate on the basis of the plasma trough level (Cmin) of less than about 1100 ng/mL in the patient; and   (d) thereafter selectively adjusting the dose of Imatinib mesylate in a manner that a Cmin of between 1100 and 2500 ng/mL of Imatinib mesylate is achieved in the patient.   
     
     
         6 . The method according to  claim 5  wherein the at least one blood sample is collected within the first 3 months of treatment. 
     
     
         7 . The method according to  claim 5  wherein the at least one blood sample is collected within the first 30 days of treatment. 
     
     
         8 . The method according to  claim 5  wherein the patient is a GIST patient with the Exon 11 KIT mutation.