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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Common side effects reported for nilotinib include GI toxicities such as abdominal pain, constipation, and diarrhea. Other ADRs include rash, abnormalities in liver function (e.g., AST, ALT, and bilirubin), hyperglycemia, hypercholesterolemia, elevated serum lipase, and headache. Myelosuppression (e.g., neutropenia, anemia, and/or thrombocytopenia) can also occur to a similar extent as for both imatinib and dasatinib.
Targeting BCR-ABL in Chronic Myelogenous Leukemia
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
In this trial, nilotinib was found to be superior to imatinib in achieving MMR and CCyR. Two doses of nilotinib (300 or 400 mg daily) were compared to imatinib 400 mg daily. At 12 months, rates of MMR were significantly higher in patients receiving 300 mg of nilotinib (44%) or 400 mg of nilotinib (43%) twice daily than imatinib (22%). Rates of CCyR achieved by 12 months were also significantly higher for nilotinib versus imatinib (78–80% versus 65%; P < 0.001), and CCyR and MMR occurred sooner in the nilotinib arms. At 5 years, the cumulative incidence was 77% in both the nilotinib arms, compared with 60% in the imatinib arm. Notably, the incidence of transformation to AP or BP were 3.9%, 2.1% and 7.4% for nilotinib 300 mg, nilotinib 400 mg and imatinib 400 mg, respectively [25, 58].
Alternative drug combination to treat chronic myeloid leukemia resistance in developing countries
Published in Ade Gafar Abdullah, Isma Widiaty, Cep Ubad Abdullah, Medical Technology and Environmental Health, 2020
A.F. Sumantri, A. Oehadian, M.H. Bashari
Nilotinib is designed as a BCR-ABL inhibitor, potentially 30 times more potent than imatinib in vitro, with specification against BCR-ABL. Nilotinib is used in CML patients with resistant or intolerant imatinib in chronic and acceleration phases (not for the blast and Ph + LLA phases) at a dose of 400 mg twice daily (O’Dwyer et al. 2009).
Tenosynovial giant cell tumors (TGCT): molecular biology, drug targets and non-surgical pharmacological approaches
Published in Expert Opinion on Therapeutic Targets, 2022
Geert Spierenburg, Lizz van der Heijden, Kirsten van Langevelde, Karoly Szuhai, Judith V.G.M. Bovée, Michiel A.J. van de Sande, Hans Gelderblom
Nilotinib was the first drug whose efficacy and safety was investigated in an open-label, phase II trial for non-resectable D-TGCT[83]. Nilotinib inhibits tyrosine kinases Abl, KIT, PDGFR and CSF1R. Patients received 400 mg orally twice daily until treatment discontinuation or completion of 1 year of treatment. Of 51 evaluable patients, 49 (96%) were progression-free at 12 weeks and 46 (90%) at 24 weeks. After one year of treatment, the best objective response was partial response achieved in three patients (6%) and stable disease in 46 (90%). In total, ten (20%) patients had had disease progression during the 1-year study period. Six patients discontinued nilotinib due to disease progression; five patients due to toxicities. Headache, nausea, increased alanine aminotransferase (ALT) concentrations, fatigue and asthenia, were the most common AEs. Nine grade 3 AEs occurred, including hepatic disorders and toxicodermia. Post-hoc analysis showed progression-free survival in 57% at 48 months. However, secondary resection and nilotinib treatment duration had no additional effect on progression-free survival, although selection biases of patients for surgery are probable.
Dementia with Lewy bodies: emerging drug targets and therapeutics
Published in Expert Opinion on Investigational Drugs, 2021
Evans D. Pope, Laura Cordes, Jiong Shi, Zoltan Mari, Boris Decourt, Marwan Noel Sabbagh
Nilotinib is a chemotherapeutic agent typically used to treat leukemia. This tyrosine kinase inhibitor may prove to be efficacious in the treatment of DLB, PDD, and AD. A small proof of concept study by Pagan et al. found that nilotinib can dramatically alter the course of PD in humans, with little to no harmful adverse events [22]. Nilotinib disintegrates α-syn and hyper-phosphorylated Tau (p-Tau) in PD mouse models, ameliorating the neurodegenerative effects induced by these harmful proteins on the brain and cognitive functioning [23]. Preclinical evidence for potential benefits include autophagic clearance of neurotoxic proteins (α-synuclein, tau, amyloid-β) and protective effects on neural cells. Nilotinib doses between 150 and 300 mg have been shown to be safe and tolerable when tested by both normal controls and PD subjects in clinical studies for PD [24]. Nilotinib targets kinases involved in the hyperphosphorylization of tau in order to clear them from neurons [25]. In addition, nilotinib has demonstrated the ability to reduce neuroinflammation accompanying neurodegenerative disease. Working in concert with bosutinib, another tyrosine kinase inhibitor, pre-plaques associated with AD, DLB, and PDD were cleared from neurons in transgenic mice, thereby delaying the onset of these neurodegenerative diseases and ameliorating their damage to neurons [26].
On the road to treatment-free remission in chronic myeloid leukemia: what about ‘the others’?
Published in Expert Review of Anticancer Therapy, 2020
Fabio Stagno, Massimo Breccia, Francesco Di Raimondo
The Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd) study investigated CP-CML patients and stratified them to receive nilotinib (NIL) 300 mg twice daily, NIL 400 mg twice daily or IM 400 mg once daily. The 5 year update revealed the following cumulative molecular response rates: 77.0% in NIL 300 mg BID, 77.2% in NIL 400 mg BID and 60.4% in IM arm achieved MMR, respectively; 65.6% (NIL 300 mg BID), 63.0% (NIL 400 mg BID) and 41.7% (IM) patients achieved MR4; 53.5% (NIL 300 mg BID), 52.3% (NIL 400 mg BID), 31.4% (IM) achieved MR4.5, respectively [25]. Therefore, in this study a rate of CML patients ranging from 11.4% for NIL 300 mg BID, 14% for NIL 400 mg BID to 18.7% for IM retained a stable MMR but not a deeper MR at 5 years.