Chemotherapy of Malignancy 379CISPLATIN
It acts by cross-linking of DNA. It also
has radiomimetic property. It is bound to
plasma proteins and is excreted slowly
unchanged in urine. It is effective in
metastatic testicular and ovarian
carcinoma, advanced bladder carcinoma
and refractory squamous cell head and neck
carcinoma.
Adverse effects include nausea, vomit-
ing, fever, anaphylactic reactions, hypokale-
mia, hypomagnesaemia, haemolysis, renal
damage, sterility, teratogenesis, ototoxicity,
peripheral neuropathy, Raynaud’s disease
and bone marrow depression.
INTERFERON ALFA
It is highly purified protein containing
165 amino acids and is manufactured by
recombinant DNA technology.
Mechanism of action is not clearly
understood but direct antiproliferative
action against tumour cells and modulation
of the host immune response may play
important roles.
It exhibits half life of 3.7-8.5 hours.
Alpha interferons are filtered through the
glomeruli and undergo rapid proteolytic
degradation during tubular reabsorption.
It is indicated in hairy cell leukemia,
AIDS related Kaposi’s sarcoma (the
detailed pharmacology and its use as
antiviral agent is discussed in chapter
‘Antiviral agents’).
Adverse effects include GI haemor-
rhage, leukopenia and elevation in liver
enzyme levels.
Recently introduced interferon a-2b is
used in chronic myeloid leukaemia, chronic
hepatitis B and C.
IMMUNOSUPPRESSANTSThe drugs like azathioprine and
cyclosporine A are used chiefly to prevent
transplant rejection and in the treatment
of autoimmune diseases. They are used to
prevent graft rejection after kidney, liver,
lung, pancreas transplant or bone marrow
transplantation.AZATHIOPRINE
It is a purine antimetabolite which has
marked effect on T-lymphocytes, suppresses
cell mediated immunity (CMI). It selectively
affects differentiation and functions of T
cells and inhibits cytolytic lymphocytes. It is
used primarily as immunosuppressant in
organ transplantation, progressive rheuma-
toid arthritis and some other autoimmune
diseases.CYCLOSPORINE
It is a cyclic polypeptide with 11 amino
acids. It selectively inhibits T-lymphocytes
proliferation, IL-2 and other cytokine pro-
duction. It is the most effective drug for
prevention and treatment of graft rejec-
tion reaction. It is used in cardiac, hepatic,
renal, bone marrow transplantation and
as second line drug in rheumatoid arthri-
tis, inflammatory bowel disease, dermato-
myositis, bronchial asthma and certain
other autoimmune diseases.
Mycophenolate mofetil, a semisynthetic
derivative of mycophenolic acid, isolated
from the mould Penicillium glaucum is used
in kidney and liver transplant patient.
Another newer compound mizoribine is
used in kidney transplantation.