Chemotherapy of Malignancy 375and blocks generation of cytidylic acid
and is a drug of choice for acute myeloid
leukaemia.
It is indicated in acute myelocytic
leukaemia, acute lymphocytic leukaemia,
chronic myeloid leukaemia (blast phase),
non-Hodgkin’s lymphoma in children,
treatment and maintenance of meningeal
neoplasms, erythroleukaemia.
Adverse effects include depression of
bone marrow which gives rise to leukopenia,
thrombocytopenia, reticulocytopenia. GI
disturbances, oral and anal ulceration,
hepatic and renal dysfunction and
peripheral neurotoxicity with high doses.
CYTOTOXIC ANTIBIOTICSThese drugs are obtained from various
microorganisms and have antitumor activity.
They act by binding to double stranded DNA
and interfere with its functions.
DACTINOMYCIN (ACTINOMYCIN D)
It is a potent antitumor antibiotic
isolated from Streptomyces organism. It
binds tightly to double stranded DNA
through intercalation between adjacent
guanine cytosine base pair and inhibit all
forms of DNA dependent RNA synthesis.
It is used in choriocarcinoma,
Hodgkin’s disease and Wilm’s tumour in
combination with irradiation.
Adverse effects include damage of
skin, alopecia, bone marrow depression,
vomiting and diarrhoea.
DOXORUBICIN
It is a cytotoxic anthracycline antibiotic
isolated from Streptomyces pneuceticus. It is
DNA intercalator and it generates free
radicals.
It is usually administered by
intravenous route. It does not cross blood
brain barrier.
Adverse effects include nausea, vom-
iting, diarrhoea, fever, red urine (harmless),
ventricular arrhythmia, severe local tissue
damage on extravasation, cardiotoxicity,
bone marrow depression, anorexia, stoma-
titis, alopecia, conjunctivitis.
It is indicated in GI tract carcinoma,
acute myeloblastic leukaemia, bronchogenic,
breast and ovarian carcinoma, soft tissue
and bone sarcomas, malignant lymphoma;
primary management of nonmetastatic
bladder carcinoma (intravesical administra-
tion), Wilm’s tumor and neuroblastoma.
Epirubicin (FARMORUBICIN) is
structurally similar to doxorubicin and is
similarly effective in the treatment of breast
cancer, lung cancer and lymphoma.BLEOMYCIN
It is a mixture of cytotoxic glycopeptide
antibiotic isolated from a strain of
Streptomyces verticillus.
It exerts its cytotoxic action by causing
fragmentation of DNA and it generates
free radicals.
It is usually administered by parenteral
route. It does not cross blood brain barrier.
Adverse effects include nausea, vom-
iting, allergic reactions, fever, anaphylaxis,
skin rash, Raynaud’s phenomenon, stoma-
titis, pulmonary fibrosis, hyperpigmenta-
tion, renal and hepatic toxicity.
Bleomycin is used as palliative and ad-
juvant to surgery and radiation therapy in