Antibiotics

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Chapter: Essential pharmacology : Anticancer Drugs

These are products obtained from microorganisms and have prominent antitumour activity. Practically all of them intercalate between DNA strands and interfere with its template function.


ANTIBIOTICS

 

These are products obtained from microorganisms and have prominent antitumour activity. Practically all of them intercalate between DNA strands and interfere with its template function.

 

Actinomycin D (Dactinomycin)

 

It is a very potent antineoplastic drug, highly efficacious in Wilms’ tumour and rhabdomyosarcoma. It has also produced good results in Mtx resistant choriocarcinoma and few other malignancies. Prominent adverse effects are vomiting, stomatitis, diarrhoea, erythema and desquamation of skin, alopecia and bone marrow depression.

 

Dose: 15 μg/kg i.v. daily for 5 days.

 

DACMOZEN 0.5 mg/vial inj.

 

Daunorubicin (Rubidomycin), Doxorubicin

 

These are antitumour antibiotics with quite similar chemical structures. However, utility of daunorubicin is limited to acute leukaemia (in which it is highly active) while doxorubicin, in addition, is effective in many solid tumours. They are capable of causing breaks in DNA strands by activating topoisomerase II and generating quinone type free radicals. They have mutagenic and carcinogenic potential. Maximum action is exerted at S phase, but toxicity is usually exhibited in G2 phase.

 

Both these antibiotics produce cardiotoxicity as a unique adverse effect. This can manifest either acutely with ECG changes, arrhythmias and hypotension which are reversible, or be delayed—congestive heart failure (related to the total dose administered). CHF is due to cardiomyopathy and may be fatal. Marrow depression, alopecia, stomatitis, vomiting and local tissue damage (on extravasation) are other adverse effects.

 

Daunorubicin: 30–60 mg/m2 BSA i.v. daily for 3 days, repeat weekly.

 

DAUNOCIN, DAUNOMYCIN 20 mg/vial inj. Doxorubicin: 60–75 mg/m2 BSA slow i.v. injection every 3 weeks; ADRIAMYCIN, DOXORUBICIN, ONCODRIA 10 mg, 50 mg per vial inj.

 

Mitoxantrone

 

A recently introduced analogue of doxorubicin with lower cardiotoxicity, probably because it does not produce quinone type free radicals. It has a narrow range of utility: in acute nonhaemolytic leukaemia, chronic myelogenous leukaemia, nonHodgkin lymphoma and carcinoma breast. Though cardiomyopathy can occur, major toxicity is marrow depression and mucosal inflammation.

 

ONCOTRON 20 mg/10 ml inj; 14 mg/m2 single i.v. dose, repeat at 3 weeks.

 

Bleomycin

 

This is a mixture of closely related glycopeptide antibiotics having potent antitumour activity. It chelates copper or iron, produces superoxide ions and intercalates between DNA strands—causes chain scission and inhibits repair. It is highly effective in testicular tumour and squamous cell carcinoma of skin, oral cavity, head and neck, genitourinary tract and esophagus; also useful in Hodgkin’s lymphoma.

 

Mucocutaneous toxicity and pulmonary fibrosis, but little myelosuppression are the special features.

 

Dose: 30 mg twice weekly i.v. or i.m. (total dose 300–400 mg); BLEOCIN, ONCOBLEO 15 mg inj.

 

Mitomycin C

 

This highly toxic drug is used only in resistant cancers of stomach, cervix, colon, rectum, bladder, etc. It is transformed intracellularly to a form which acts as an alkylating agent and kills cells in G1M phases. Bone marrow and g.i.t. are the primary targets of toxicity.

 

Dose: 10 mg/m2 BSA, infused i.v. in one day or divided in 5 and infused over 5 days. MITOMYCINC 2, 10 mg inj.

 

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