Monitoring of Suspected Adverse Drug Reactions in Oncology Unit ...

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701
because of their significant anticancer activity against certain solid tumors as well as the fact that they are
minimally toxic to the bone marrow unlike most other anticancer agents.
Bleomycin has been found to profoundly inhibit DNA synthesis while RNA and protein synthesis are
much less affected. Bleomycin usually produces a block in the early G 2 phase of the cell cycle. The
cytotoxic activity results from the ability to cause fragmentation of DNA. Single strand breaks occur
predominantly but double strand breaks can also occur. Damage to the DNA correlates with the cytotoxic
effect of the drug. Bleomycin has two major domains in its structure. One portion interacts with DNA and
one binds iron. Both iron and oxygen are required for bleomycin to degrade DNA. The drug binds Fe ++ and
binds DNA by intercalation between GT or GC bases, and acts as a ferrous oxidase (Fe ++ to Fe +++ ) resulting
in production of oxygen free radicals that cleave DNA.
Bleomycin is given parenterally, by IV or intramuscular (IM) routes. After administration relatively
high concentrations of the drug are found in the skin and lungs. These organs are major sites of bleomycin
toxicity. The primary route of excretion is renal and renal failure increases risk of toxicity. As much as twothirds
of the drug is excreted in the urine within 24 hours. Bleomycin is rapidly inactivated by a tissue
enzyme, bleomycin hydrolase, which cleaves the amide bond of the aminoalanine moiety. Its activity is
higher in drug-resistant tumors. Particularly low levels of the drug inactivating enzyme are found in skin
and lung, and consequently high levels of biologically active drug are found in these two tissues.
Bleomycin is highly active against squamous cell tumors of the head, neck and lungs. It is also highly
effective against germ cell tumors of the testis and ovary. It is often used to treat testicular carcinomas
along with cisplatin and vinblastine. It is also active against Hodgkin's disease and other lymphomas where
it is often included in the ABVD regimen.
Toxicity:
Bleomycin is marrow sparing and is not immunosuppressive and is therefore a useful compound to use
in combination drug protocols. In the usual doses, the gastrointestinal tract , liver, kidneys and CNS are
also not affected. Despite these advantages bleomycin is quite toxic – the most common toxicity involves
the skin and mucous membranes. Oral mucositis is dose related and common in the more aggressive
regimens. Alopecia occurs in about 10 - 20% of patients. Toxic reactions of the skin include
hyperpigmentation, sclerotic changes with collagen infiltration, edema and erythema of the hands and feet.
These cutaneous changes are reversible when the drug is discontinued. Pulmonary toxicity is dose-limiting
and the most severe toxicity associated with use of bleomycin. Symptoms include dyspnea, tachypnea, and
a nonproductive cough. Fine rales are heard at the base of the lungs and radiography often shows a patchy
basilar infiltrate and in some cases fibrosis. The overall incidence of pulmonary toxicity is about 10% with
fatalities occurring in about 1% of patients. There is an increasing incidence when the total dose of
bleomycin goes above 400 units. It occurs more commonly in patients with compromised renal function
and when the drug is used with cisplatin which is itself nephrotoxic. Extreme caution is employed in
anyone having pre-existing pulmonary disease.
Other toxicities of bleomycin include nausea, vomiting, anorexia, drug-induced fever and chills. These
effects are usually seen within the first few hours of bleomycin therapy. About 1% of lymphoma patients
develop allergic reactions similar to anaphylaxis. For this reason, lymphoma patients are given 2 units or
less for the first 2 doses. If no acute reactions occur, the regular dosage schedule may be followed.
Plicamycin (mithramycin) is an antibiotic derived from Streptomyces plicatus. It is part of a group of drugs
referred to as chromomycin antibiotics. It is rarely used in cancer chemotherapy because of its toxicity. Its
use is now limited to the treatment of hypercalcemia associated with malignancy where it is used in lower
dosage than that used for the treatment of tumors.
Platinum coordination compounds
Cisplatin and carboplatin are among a number of platinum coordination complexes with antitumor
activity. Recently oxaliplatin was put on the market.
The platinum compounds are DNA cross-linking agents similar to but not identical to the alkylating
agents. They exchange chloride ions for nucleophilic groups of various kinds. Both the cis and trans
isomers do this but the trans isomer is known to be biologically inactive for reasons not completely
understood. To possess antitumor activity a platinum compound must have two relatively labile cis-
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