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Management of Side Effects

Leukemia Insights - Spring 2011

Some of the most common adverse events observed with tyrosine kinase inhibitors and suggested management options37 are listed in the following table.

The most common adverse event seen with tyrosine kinase inhibitors is myelosuppression, with grade 3 or 4 neutropenia (absolute neutrophil count < 1 x109/L) and thrombocytopenia (platelet count < 50 x 109/L) in up to  30% of patients, and anemia in 5% to 15% of patients. Myelosuppression most often occurs early during the course of therapy (first 2-3 weeks) and is transient. For those patients who develop grade 3 or 4 neutropenia or thrombocytopenia, temporary interruption of therapy is recommended37. Therapy can resume once the counts recover to levels above those defining grade 3 cytopenias.

If recovery occurs within 2 weeks, treatment can be reinitiated at the same dose; however, a dose reduction is recommended if recovery takes longer than 2 weeks. Hematopoietic growth factors –filgrastim for neutropenia, epoetin alfa for anemia, and oprelvekin for thrombocytopenia have been reported to benefit patients with recurrent myelosuppression that limits proper administration of therapy38. However, the long-term safety of this approach is not known. In the near future, a clinical trial will be initiated investigating the role of eltrombopag, an agonist of the c-mpl receptor, in correcting  thrombocytopenia in patients whose CML therapy is limited by recurrent low platelet counts.

Management of the Most Common Nonhematologic Adverse Events Observed During Therapy with Tyrosine Kinase Inhibitors

Adverse EventManagement
Nausea/vomiting
  • Antiemetics as needed
  • Take imatinib with food, abundant fluids
Diarrhea
  • Use loperamide or diphenoxylate and atropine
Peripheral edema
  • Diuretics as needed
  • Monitor electrolytes if diuretics are used
Periorbital edema
  • Steroid-containing cream
  • Surgical management frequently followed by recurrence
Skin rash
  • Symptomatic management (e.g. diphenhydramine), topical or systemic steroids
  • Adequate sun protection
Muscle cramps
  • Quinine or tonic water; calcium gluconate
  • Electrolyte replacement as needed
Arthralgias, bone pain
  • Nonsteroidal antiinflammatory agents
  • Nonsteroidals not recommended for patients taking dasatinib
Elevated transaminases
  • Treatment interruption until recovery to grade 1 or less, then reduce dose
Hyperbilirubinemia
  • Treatment interruption: Common with nilotinib among patients with Gilbert’s syndrome, with minimal clinical consequences
  • Monitor
Elevated lipase/amylase
  • Clinical evaluation for signs or symptoms of pancreatitis
  • If no evidence of pancreatitis, continued monitoring
Hypophosphatemia
  • Replacement therapy; monitor closely
QTc prolongation
  • Assess before starting therapy and correct any electrolyte abnormalities
  • Avoid coadministration of other agents that may prolong QTc
  • Consider alternative therapies in patients with significant QTc prolongation despite these measures
Pleural effusion
  • Treatment interruption, diuretics
  • Corticosteroids may be of benefit to some patients
  • Thoracentesis when unresponsive or with major symptoms

© 2014 The University of Texas MD Anderson Cancer Center