Tyrosine proteinkinase inhibitors
• Imatinib is a novel antineoplastic drug which inhibits the tyrosine
protein kinases in chronic myeloid leukaemia (CML) cells.
• Used for the treatment of CML in blast crisis as well as GI stromal
• Pharmacokinetics: The drug is very well absorbed orally. It undergoes
metabolism by the CYP450 system to several compounds, of which the
N-demethyl derivative is active. Excretion is predominantly through
• Adverse effects are fluid retention, edema, vomiting, abdominal pain,
myalgia , liver damage, hepatotoxicity, and thrombocytopenia or
• Dose: 400 mg/day with meal; accelerated phase of CML 600-800
EGF (epidermal growth factor receptor)
• It is approved for the treatment of non–small cell lung cancer.
• Gefitinib is usually used as a single agent.
• PK: Oral administration. Metabolism in the liver by the CYP450
enzyme CYP3A4 and excreted through feces.
• The most common adverse effects are diarrhea, nausea, and
acne-like skin rashes. A rare but potentially fatal adverse effect
is interstitial lung disease, which presents as acute dyspnea with
Unarmed monoclonal antibody
Rituximab is a chimeric monoclonal antibody against, which is primarily
surface the immune system B cells.
• Pharmacokinetics: Rituximab is administered as two 1000-mg IV infusions
separated by 2 weeks. To reduce the severity of infusion reactions,
methylprednisolone at 100 mg IV or its equivalent is administered 30 minutes
prior to each infusion. The mean terminal elimination half-life after the second
dose is 19 days.
• Adverse effects: Infusion reactions (that is, urticaria, hypotension, and
angioedema) are the most common complaints with this agent and typically
occur during the first infusion. If the infusion is to be continued, then the rate
of infusion should be reduced by 50 percent after symptoms have completely
resolved. Others: Cardiac arrest, cytokine release syndrome , tumor lysis
syndrome and causing acute renal failure.
• Use: Hematological cancers, autoimmune diseases and anti-rejection
treatment for organ transplants.
• They have gained favor in the treatment of breast
they are more potent
they are more selective than aminoglutethimide
they do not need to be supplemented with hydrocortisone
they do not predispose to endometrial cancer
they are devoid of the androgenic side effects that occur with
the steroidal aromatase inhibitors
• Use: first-line drugs in other countries for the
treatment of breast cancer
• primarily used in acute childhood leukaemia and
They produce symptomatic relief
in carcinoma prostate which is an
• Estrogen antagonist
• Used for firstline therapy in
the treatment of estrogen
• Approved only for 5 years of
• PK: orally effective,
metabolized in liver, excreted
through the bile into the feces
Hot fl ashes, nausea,
skin rash and vaginal
the potential to cause
Aromatase inhibitors: Letrozole, • Prevent relapse of breast cancer after
partial mastectomy and radiation
palliative effect in advanced/metastatic cases
Wont cause bone marrow depression
GnRH analogues: Nafarelin,
Indirectly inhibit estrogen/ androgen
secretion by suppressing FSH and LH release
from pituitary and have palliative effect in
advanced estrogen/ androgen
dependent carcinoma breast/prostate.
Temporary remission in some cases of
recurrent (after surgery /radiotherapy) and
metastatic endometrial carcinoma