Drug Detail

Information about Sprycel

Generic Name
Brand Name (US)
Bristol-Myers Squibb
Drug Type
Tyrosine Kinase Inhibitor
Approval Status
Approved for a non-GIST cancer
Imatinib-resistant CML
Overall Strategy
KIT Protein Based + Oncogenic Signal Path Based
Block KIT + Block KIT Signal Path
Drug Category
KIT/PDGFRA inhibitor + SRC inhibitor

Approved for: Treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib. Dastinib is noted in the NCCN guidelines as a therapy with activity in GIST (V2.2012), however, dasatinib is not FDA approved for GIST. A phase I combination trial of dasatinib and ipilimumab for Sarcoma and GIST started in 2012.
Targets: Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. Dasatinib has been show to inhibit the PDGFRA exon 18 mutation, D842V. This mutation is insensitive to most other kinase inhibitors including imatinib and sunitinib, however, a more specific D842V inhibitor, crenolanib, is now in phase II trials (2011).
Dosage: 100 mg once daily for chronic phase CML or 140mg/day divided into two doses per day (BID) for accelerated phase CML, myeloid or lymphoid blast phase CML, or PH+ ALL.
Side effects: * The most frequently reported adverse reactions (reported in >20% of patients) included fluid retention events (37%), diarrhea (31%), headache (24%), skin rash (22%), nausea (22%), hemorrhage (21%), fatigue (21%), and dyspnea (20%)
* The most frequently reported serious adverse reactions included pleural effusion (9%), febrile neutropenia (4%), gastrointestinal bleeding (4%), pyrexia (3%), pneumonia (3%), dyspnea (3%), infection (2%), diarrhea (2%), congestive heart failure (2%), sepsis (1%), and pericardial effusion (1%)
* Grade 3/4 laboratory abnormalities in clinical studies in chronic phase CML included neutropenia (46%), thrombocytopenia (41%), anemia (18%), hypophosphatemia (10%), and hypocalcemia (2%)
* Grade 3/4 elevations of transaminase or bilirubin and Grade 3/4 hypocalcemia and hypophosphatemia were reported in patients with all phases of CML, but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML and Ph+ ALL
o Elevations in transaminase or bilirubin were usually managed with dose reduction or interruption
o Patients developing Grade 3/4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation
o Proton pump inhibitors (PPI) interfere with the proper absorption of dasatinib, decreasing dasatinib levels by half.
This suggests that if you are taking one of these drugs to reduce stomach acid, it may reduce the amount of dasatinib in your blood by half. This should be a discussion point with your doctor if you are taking both.

See this link in the Links section below (Effect of a proton pump inhibitor . . . )

The following excerpt is from Wikipedia:

Proton pump inhibitors (or "PPI"s) are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today.

These drugs are utilized in the treatment of many conditions such as:

* Dyspepsia
* Peptic ulcer disease (PUD)
* Gastroesophageal reflux disease (GORD/GERD)
* Extraesophageal reflux disease
* Barrett's esophagus
* prevention of stress gastritis
* Gastrinomas and other conditions that cause hypersecretion of acid
* Zollinger-Ellison syndrome

Clinically used proton pump inhibitors:

* Omeprazole (brand names: Losec, Prilosec, Zegerid, ocid, Lomac, Omepral, Omez)
* Lansoprazole (brand names: Prevacid, Zoton, Inhibitol, Levant, Lupizole)
* Dexlansoprazole (brand name: Kapidex)
* Esomeprazole (brand names: Nexium, Esotrex)
* Pantoprazole (brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan)
* Rabeprazole (brand names: Rabecid, Aciphex, Pariet, Rabeloc. Dorafem: combination with domperidone



Dasatinib inhibits KIT D816V mutation-an imatinib-resistant activating mutation




Sprycel reimbursement support (Destination Access)


Sprycel prescribing information (PDF)


Dasatinib inhibits PDGFRA D842V mutation - Debiec-Rychter - 2008


Dasatinib inhibits activity of wild-type, juxtamembrane and activation loop mutant KIT (Heinrich, et al)


FDA drug information page (technical information about the drug approval, etc)


Effect of a proton pump inhibitor on the pharmacokinetics of imatinib (mentions that dasatinib levels are highly affected by PPIs).


The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib


FDA: Increased Pulmonary Arterial Hypertension Risk Seen With Dasatinib


FDA website: Sprycel (dasatinib): Drug Safety Communication - Risk of Pulmonary Arterial Hypertension


Severe adverse events associated with the use of second-line BCR/ABL tyrosine kinase inhibitors: preferential occurrence in patients with comorbidities


Disintegration of chemotherapy tablets (including dasatinib) for oral administration in patients with swallowing difficulties


Activity of dasatinib against L576P KIT mutant melanoma: Molecular, cellular, and clinical correlates

Trials of this drug


Phase I (PH I) Mad Refractory Solid Tumor Study


Study of BMS-354825 in Patients With Solid Tumors


Dasatinib as First-Line Therapy in Treating Patients With Gastrointestinal Stromal Tumors


Trial of Dasatinib in Advanced Sarcomas

Trial results

  Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumor: A multicenter, 2-stage phase 2 trial (Swiss Group for Clinical Cancer Research 56/07) Full-text article
  A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST)
  ASCO 2010 - Results of a Sarcoma Alliance for Research through Collaboration (SARC) phase II trial of dasatinib in previously treated, high-grade, advanced sarcoma.
  Phase I dose-escalation study of the SRC and multi-kinase inhibitor BMS-354825 in patients (pts) with GIST and other solid tumors
  BMS - Final Clinical Study Report for CA180003

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