McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

TABLE 14.6

DRUGS IN FOCUS Cancer cell–specific agents (continued)

Drug name

Dosage/route

Usual indications

Protein tyrosine kinase inhibitors (continued) temsirolimus (Torisel)

25 mg IV, infused over 30–60 minutes once per week

Treatment of advanced renal cell carcinoma Special considerations: monitor lung function, blood glucose, renal function; may experience slowed healing; avoid grapefruit juice, St John’s wort Treatment of locally advanced or metastatic non– small cell lung cancer after failure of at least one other drug regimen; first-line treatment of pancreatic cancer when used in combination with gemcitabine Special considerations: serious-to-fatal interstitial lung disease—monitor with hepatic impairment; do not use during pregnancy Treatment of multiple myeloma in people with disease progression after two other therapies Special considerations: may cause peripheral neuropathies, hypotension and bone marrow suppression; do not use during pregnancy

Epidermal growth factor inhibitor erlotinib (Tarceva)

150 mg/day PO 1 hour before or 2 hours after meal

Proteasome inhibitor bortezomib (Velcade)

1.3 mg/m 2 by bolus IV injection on days 1, 4, 8 and 11, followed by 10 days of rest, then repeat

P rotein tyrosine kinase inhibitors The protein kinase inhibitors (Table 14.6) act on specific enzymes that are needed for protein building by specific tumour cells. Blocking of these enzymes inhibits tumour cell growth and division. Each drug that has been developed inhibits a very specific protein kinase and acts on very specific tumours. They do not affect healthy human cells, so the person does not experience the numerous adverse effects associated with antineoplastic chemotherapy. Imatinib ( Glivec ), the first drug approved in this class, is given orally and is approved to treat chronic myelo­ cytic leukaemia (CML). Individuals who have CML and who have been switched to imatinib after tradi­ tional chemotherapy have been amazed at how good they feel and how much they have recovered from the numerous adverse effects of the traditional chemo­ therapy. Long-term effects are not yet known because the drug is relatively new. Unfortunately, this drug is expensive although available through the Pharma­ ceutical Benefit Scheme. People prescribed this drug may need support and assistance in obtaining finan­ cial help. The protein tyrosine kinase inhibitors that are available include bortezomib ( Velcade ), erlotinib ( Tarceva ), everolimus ( Afinitor, Certican ), gefitinib ( Iressa ), imatinib ( Glivec ), lapatinib ( Tykerb ), nilotinib ( Tasigna ), sorafenib ( Nexavar ), sunitinib ( Sutent ) and temsirolimus ( Torisel ).

E pidermal growth factor inhibitor In 2006, the Australian Therapeutic Goods Adminis­ tration (TGA) approved erlotinib ( Tarceva ), a drug that inhibits cell epidermal growth factor receptors. This growth factor is found on normal and cancerous cells but is more abundant on rapidly growing cells. P roteasome inhibitor TGA have approved bortezomib ( Velcade ) for the treat­ ment of multiple myeloma in people whose disease has progressed after one other standard therapy. This drug inhibits proteasome in human cells, a large protein complex that works to maintain cell homeostasis and protein production. Without it, the cell loses homeosta­ sis and dies. This drug was shown to delay growth in selected tumours. Therapeutic actions and indications Imatinib, an oral antineoplastic drug, is a protein tyrosine kinase inhibitor that selectively inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Blocking this enzyme inhibits proliferation and induces cell division in Bcr-Abl–positive cell lines, as well as in new leukaemic cells, thereby inhibiting tumour growth in CML suf­ ferers in blast crisis. It also inhibits a specific receptor site in individuals with gastrointestinal stromal tumour (GIST). Because of its specific effects on these tumour