As another example, one isoform of MGRN1 with significant e

[jy9202]

Mus culoskeletal AEs were reported as separate categories; 10% of patients experienced muscle cramp ARN-509 構造 and 10% experienced joint pain, In the GIMEMA study, 41% of patients taking nilotinib experienced bone muscle joint pain, of which 4% were grade 3. In addition, 30% experi enced headache and 22% experienced fatigue, Biochemical abnormalities Rates of biochemical abnormalities vary in patients receiving different BCR ABL inhibitors and seem to be most common during nilotinib treatment. In the DASI SION trial, grade 3 4 hypophosphatemia occurred in 4% of patients treated with dasatinib compared with 21% of the patients treated with imatinib.

Rates of other grade 3 4 biochemical abnormalities were low in both treat ment arms, including markers of hepatic toxicity and pancreatic toxicity, Rates of all grade biochemical abnormalities were not reported, Four imatinib treated patients AUY922 構造 but no dasatinib treated patients discon tinued therapy because of biochemical abnormalities, In the MDACC study of dasatinib, hypophosphate mia occurred in 6% of patients, hypergly cemia occurred in 24%, and elevated ALT or AST occurred in 16% and 15%, respectively, In the ENESTnd trial, more nilotinib treated patients than imatinib treated patients had biochemical abnorm alities associated with liver and pancreatic toxicity. With nilotinib 300 mg BID or 400 mg BID or imatinib, ALT was elevated in 66% vs 73% vs 20% of patients, respec tively, AST was elevated in 40% vs 48% vs 23%, and bilirubin was elevated in 53% vs 62% vs 10%, Elevated lipase was observed in 24 29% of patients receiving nilotinib compared with 11% of patients receiving imatinib, Respective rates of hyperglycemia were 36 41% vs 20% and ele vated amylase occurred in 15 18% vs 12% of patients.

Hypophosphatemia occurred ALK 阻害剤 in 32 34% of nilotinib arms and 45% of the imatinib arm, All newly occurring grade 3 4 biochemical abnormalities occurred within the first 2 months of therapy. Discontinuations due to biochem ical abnormalities occurred in 2% of both nilotinib arms and 1% of the imatinib arm, In other studies of nilotinib as front line therapy, ALT elevation occurred in 42 48% of patients, AST elevation occurred in 29 46%, and bilirubin eleva tion occurred in 39 53%, Elevated markers of pancreatic toxicity were reported in both studies.

However, hyperglycemia was more com mon in the MDACC study than elevated lipase or amylase, whereas hyperglycemia was less common in the GIMEMA study than elevated lipase or amylase, One patient in the GIMEMA study discontinued treatment following lipase elevation. Bilirubin elevation on nilotinib may be due in part to nilotinib inhibition of UGT1A1 activity. UGT1A1 cata lyzes the conjugation of hepatic bilirubin and poly morphisms in the promoter region of UGT1A1 are associated with Gilberts Syndrome, Reduced UGT1A1 expression due to polymorphisms is associated with elevation of bilirubin in plasma, UGT1A1 pro moter polymorphism has been found to increase the risk of nilotinib induced bilirubin elevation, Dose adjustments and discontinuations due to toxicity The rate of discontinuations because of drug toxicity pro vides a measure of the frequency of the most problematic AEs. In the DASISION trial, discontinuations following study drug toxicity occurred in 5.