Review of Pharmacology - 9E (2015)

CHAPTER
15
Chemotherapy C:
Antineoplastic Drugs
Neoplastic cells are quite similar to normal cells, therefore the drugs targeted to kill these
cells can also kill normal cells. As most of these drugs are acting on rapidly dividing cells, the
normal cells having quick turnover are most susceptible to toxicity. Bone marrow suppression,
alopecia and mucositis are thus commonly caused by anti-cancer drugs. New drugs targeting
specific steps in the cells are devoid of these adverse effects.
Anticancer drugs may be divided (on the basis of stage of cell cycle at which these act) into
two groups – cell cycle specific (CCS) and cell cycle non-specific (CCNS). CCS drugs are
effective when the cells are proliferating whereas CCNS drugs are effective whether the cells
are dividing or are in the resting phase.
Table 15.1: Cell cycle effects of anticancer drugs (Ref. Katzung 11/e p938)
CCS Drugs CCS Drugs CCNS Drugs
G 1
- S Etoposide Platinum compounds
S Antimetabolites Alkylating agents
G 2
- M
M
Bleomycin
Etoposide [Ref Harrison 17th/525]
Vinca alkaloids
Taxanes
Ixabepilone
Estramustine
Anthracyclines
Dactinomycin
Mitomycin
Camptothecins
Initially, the anticancer drugs were developed based on murine L1210 leukemia model. This
model has a growth fraction of 100% (i.e. all cells are actively dividing). Based on this murine
model cytotoxic drugs act with first order kinetics i.e. a constant proportion of cells are
killed with a given dose rather than constant number of cells. For example same dose of a
drug will be required to reduce tumor population from 1000 to 100 as is needed to reduce it
from 100 to 10. This is called ‘log kill hypothesis’.
However, human solid tumors donot follow this model, because, growth fraction of the
tumor is not constant but decreases exponentially with time. Growth fraction peaks when tumor
is approximately 37% of its maximum size, this model is known as Gompertzian model.
Classification
Alkylating Agents
i. Nitrogen mustards: Mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil
ii.
iii.
iv.
Ethylenimines: Thio-TEPA, hexamethylmelamine (altretamine)
Alkyl sulfonates: Busulfan
Nitrosoureas: Carmustine, lomustine, streptozocin
v. Triazines : Procarbazine, dacarbazine, temozolomide
Platinum compounds
Cisplatin, carboplatin, oxaliplatin.
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