220
P A R T 2
Chemotherapeutic agents
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
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
Epidermal growth factor inhibitor
erlotinib (Tarceva)
150 mg/day PO 1 hour before or
2 hours after meal
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
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
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
