Chemotherapic drugs


Drugs employed in chemotherapy represent an heterogeneous group of substances that inhibit the proliferation of malignant cells with different mechanisms, mainly genotoxic. These do not spare normal highly proliferating tissues (piliferous bulb, intestinal epithelium, bone marrow).
The main groups of chemotherapic drugs include:
- alkylation agents (cyclophosphamide, cisplatinum, carboplatinum, ect.);
- antimetabolites (azathioprine, fluorouracil, methotrexate, etc.);
- antimitotics (vincristine, vinblastine);
- antibiotics (actinomycin, bleomycin, daunomycin);
- enzymes (L-asparaginase).

Most of these substances have been proved to be mutagenic, carcinogenic and teratogenic in experimental systems.


Antineoplastic drugs usually irritate skin and mucous membranes. Furthermore, they can provoke local toxic effects (phlebitis, allergies, tissue necrosis) and systemic toxic effects (allergies, organ toxicity).

In the following table the local effect of the main antineoplastic drugs in case of discharge(?) is indicated.

- Not blister
- Not irritants

Irritants

Blister

L-Asparaginase
Bleomycin
Cyclophosphamide
Cytarabine
Methotrexate
Thiotepa

Carmustine
Dacarbazine
5-Fluorouracil
Cisplatinum

Daunorubicin
Doxorubicin
Epidoxorubicin
Etoposide
Mitomycin C
Mitoxantrone
Vinblastine
Vincristine
Vindesine


Among the systemic toxic effects, toxicity on organ and apparatuses of the treated patient must be mentioned.
Short term effects include alopecia, stomatitis, leucopenia and anaemia; medium term effects are liver disease, nephrosis and bone marrow aplasia; long term effects include the arising of a second tumour and myocardium sclerosis.
Among the most serious side effects of these drugs there are both mutation induction and carcinogenic effects. According to IARC (International Agency for Research on Cancer) many antitumoural drugs can provoke tumours. In fact, cases of second tumours in patients treated with antiblastic drugs have been reported (especially acute non lymphoblastic leukemia).
Antitumoural drugs taken into account by IARC are reported in the following table:
Group 1: carcinogenic to humans

1,4-Butanediol dimethanesulfonate (Myleran)
Cyclophosphamide
Chlorambucil
1(2-Chloroethyl)-3(4-Methylcyclohexyl)-1-Nitrosourea
Estrogens
Melphalan
MOPP
Treosulfan

Group 2: probably carcinogenic to humans

sufficient evidence
Adriamycin
Bischloroethyl nitrosourea (BCNU)
Cisplatin
1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (CCNU)
Procarbazine hydrochloride
Thiotepa

limited evidence
Bleomycin
Dacarbazine
Daunomycin

As far as the potential exposure of the health workers is concerned, the enormous difference between therapeutical doses and doses resulting from professional exposure must be emphasized. Up to the present day reliable carcinogenic effects have been found only in the treated patients and not in health workers.
Cytogenetic effects, such as an increase in chromosomic aberrations and exchange of sister chromatids have been shown in groups of nurses and pharmacy personnel that had been handling the drugs without taking the recommended precautions, whereas they have not been observed in the groups that complied with the required hygienic measures.
As far as the potential effects of professional exposure to these drugs on the outcome of the first three months of pregnancy are concerned, some case-control studies have shown a double risk of miscarriages and malformations on the offspring, whereas other more recent studies have shown negative results.




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Chemotherapic drugs