Available agents include:

 Daunorubicin (Daunomycin)
 Daunorubicin (liposomal)
 Doxorubicin (Adriamycin)
 Doxorubicin (liposomal)
 Epirubicin
 Idarubicin
 Valrubicin, used only to treat bladder cancer
 Mitoxantrone, anthracycline analog
Since they are antibiotics, anthracyclines can kill or inhibit the growth of bacteria, but because
they are so toxic to humans, they are never used to treat infections.
Mechanism of action
Anthracycline has three mechanisms of action:
1. Inhibits DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA
strand, thus preventing the replication of rapidly-growing cancer cells.[6]
2. Inhibits topoiosomerase II enzyme, preventing the relaxing of supercoiled DNA and thus
blocking DNA transcription and replication.
3. Creates iron-mediated free oxygen radicals that damage the DNA and cell membranes
Cardiotoxicity
As well as many of the expected adverse reactions of chemotherapeutic agents, anthracyclines
are notorious for causing cardiotoxicity. This cardiotoxicity may be caused by many factors,
which may include interference with the ryanodine receptors of the sarcoplasmic reticulum in the
heart muscle cells, free radical formation in the heart or from buildup of metabolic products of
the anthracycline in the heart. The cardiotoxicity often presents as ECG changes and
arrhythmias, or as a cardiomyopathy leading to heart failure (sometimes presenting many years
after treatment). This cardiotoxicity is related to a patient's cumulative lifetime dose. A patient's
lifetime dose is calculated during treatment, and anthracycline treatment is usually stopped (or at
least re-evaluated by the oncologist) upon reaching the maximum cumulative dose of the
particular anthracycline.
There exists evidence that the effect of cardiotoxicity increases in long term survivors, from 2%
after 2 years to 5% after 15 years. [7]
Dexrazoxane is a cardioprotectant that is sometimes used to reduce the risk of cardiotoxicity; it
has been found to reduce the risk of anthracycline cardiotoxicity by about two thirds, without
affecting response to chemotherapy or overall survival.[8] The liposomal formulations of
daunorubicin and doxorubicin appear to be somewhat less toxic to cardiac tissue than the non-
liposomal form.

Mechanism of action
Bleomycin acts by induction of DNA strand breaks.[4] Some studies suggest that bleomycin also
inhibits incorporation of thymidine into DNA strands. DNA cleavage by bleomycin depends on
oxygen and metal ions, at least in vitro. It is believed that bleomycin chelates metal ions
(primarily iron) producing a pseudoenzyme that reacts with oxygen to produce superoxide and
hydroxide free radicals that cleave DNA. In addition, these complexes also mediate lipid
peroxidation and oxidation of other cellular molecules.
Side effects
The most serious complication of bleomycin is pulmonary fibrosis and impaired lung function. It
has been suggested that bleomycin induces sensitivity to oxygen toxicity[5] and recent studies
support the role of the proinflammatory cytokines IL-18 and IL-1beta in the mechanism of
bleomycin-induced lung injury.[6] Past history of treatment with bleomycin should therefore
always be disclosed to the anaesthetist prior to undergoing a procedure requiring general
anaesthesia.
Other side effects include fever, rash, dermatographism, hyperpigmentation, alopecia (hair loss)
and Raynaud's phenomenon (discoloration of fingers and toes)
The main use of cyclophosphamide is together with other chemotherapy agents in the treatment
of lymphomas, some forms of leukemia[2] and some solid tumors[3]. It is a chemotherapy drug
that works by slowing or stopping cell growth.

Mode of action
The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This
metabolite is only formed in cells that have low levels of ALDH.
Phosphoramide mustard forms DNA crosslinks between (interstrand crosslinkages) and within
(intrastrand crosslinkages) DNA strands at guanine N-7 positions. This leads to cell death.
Cyclophosphamide has relatively little typical chemotherapy toxicity as ALDHs are present in
relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium.
ALDHs protect these actively proliferating tissues against toxic effects phosphoramide mustard
and acrolein by converting aldophosphamide to carboxyphosphamide that does not give rise to
the toxic metabolites (phosphoramide mustard and acrolein).
Side-effects
Many people taking cyclophosphamide do not have serious side effects. Side-effects include
chemotherapy-induced nausea and vomiting (CINV), bone marrow suppression, stomach ache,
diarrhea, darkening of the skin/nails, alopecia (hair loss) or thinning of hair, changes in color and
texture of the hair, and lethargy. Hemorrhagic cystitis is a frequent complication, but this is
prevented by adequate fluid intake and Mesna (sodium 2-mercaptoethane sulfonate).

Mode of action
Tubulin is a structural protein which polymerizes to action microtubules. The cell cytoskeleton
and mitotic spindle, amongst other things, are made of microtubules. Vincristine binds to tubulin
dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests
mitosis in metaphase. The vinca alkaloids therefore affect all rapidly dividing cell types
including cancer cells, but also intestinal epithelium and bone marrow.
Uses
Vincristine is delivered via intravenous infusion for use in various types of chemotherapy
regimens. Its main uses are in non-Hodgkin's lymphoma as part of the chemotherapy regimen
CHOP, Hodgkin's lymphoma as part of MOPP, COPP, BEACOPP, or the less popular Stanford
V chemotherapy regimen, in acute lymphoblastic leukemia, and in treatment for nephroblastoma
(Wilms tumor, a kidney tumor common in children). It is also used to induce remission in ALL
with Dexamethasone and L Asparaginase. Vincristine is occasionally used as an
immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or
chronic idiopathic thrombocytopenic purpura (ITP). It is used in combination with prednisone to
treat childhood leukemia
Side effects
The main side-effects of vincristine are peripheral neuropathy, hyponatremia, constipation and
hair loss.
Peripheral neuropathy can be severe, and hence a reason to avoid, reduce, or stop the use of
vincristine. One of the first symptoms of peripheral neuropathy is foot drop: a person with a
family history of foot drop and/or Charcot-Marie-Tooth disease (CMT) may benefit from genetic
testing for CMT before taking vincristine.[1]
Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly
dangerous, with a mortality rate approaching 100 percent. The medical literature documents
cases of ascending paralysis due to massive encephalopathy and spinal nerve demyelination,
accompanied by intractable pain, almost uniformly leading to death; a handful of survivors were
left with devastating neurological damage with no hope of recovery. Rescue treatments consist of
washout of the cerebrospinal fluid and administration of protective medications.[2] A significant
series of inadvertent intrathecal vincristine administration occurred in China in 2007 when
batches of cytarabine and methotrexate (both often used intrathecally) manufactured by the
company Shanghai Hualian were found to be contaminated with vincristine.

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based

chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas
(e.g. small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors. It was the
first member of a class of anti-cancer drugs which now also includes carboplatin and oxaliplatin.
These platinum complexes react in vivo, binding to and causing crosslinking of DNA which
ultimately triggers apoptosis (programmed cell death).
Pharmacology
Following administration, one of the chloride ligands is slowly displaced by water (an aqua
ligand), in a process termed aquation. The aqua ligand in the resulting [PtCl(H2O)(NH3)2]+ is
itself easily displaced, allowing the platinum atom to bind to bases. Of the bases on DNA,
guanine is preferred. Subsequent to formation of [PtCl(guanine-DNA)(NH3)2]+, crosslinking can
occur via displacement of the other chloride ligand, typically by another guanine.[1] Cisplatin
crosslinks DNA in several different ways, interfering with cell division by mitosis. The damaged
DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves
impossible. Recently it was shown that the apoptosis induced by cisplatin on human colon cancer
cells depends on the mitochondrial serine-protease Omi/Htra2[2]. Since this was only
demonstrated for colon carcinoma cells, it remains an open question if the Omi/Htra2 protein
participates in the cisplatin-induced apoptosis in carcinomas from other tissues.
Most notable among the changes in DNA are the 1,2-intrastrand cross-links with purine bases.
These include 1,2-intrastrand d(GpG) adducts which form nearly 90% of the adducts and the less
common 1,2-intrastrand d(ApG) adducts. 1,3-intrastrand d(GpXpG) adducts occur but are
readily excised by the nucleotide excision repair (NER). Other adducts include inter-strand
crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's
activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been
advanced as a mechanism of interfering with mitosis, although this is probably not its primary
method of action.
Note that although cisplatin is frequently designated as an alkylating agent, it has no alkyl group
and so cannot carry out alkylating reactions. It is correctly classified as alkylating-like
Cisplatin has a number of side-effects that can limit its use:
 Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the
patient's creatinine clearance (a measure of renal function) is reduced. Adequate
hydration and diuresis is used to prevent renal damage. The nephrotoxicity of platinum-
class drugs seems to be related to reactive oxygen species and in animal models can be
ameliorated by free radical scavenging agents (e.g., amifostine). Nephrotoxicity is a dose-
limiting.
 Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies
before and after treatment.
 Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents, but
this symptom is managed with prophylactic antiemetics (ondansetron, granisetron, etc.)
in combination with corticosteroids. Aprepitant combined with ondansetron and
dexamethasone has been shown to be better for highly emetogenic chemotherapy than
just ondansetron and dexamethasone.
 Ototoxicity (hearing loss): unfortunately there is at present no effective treatment to
prevent this side effect, which may be severe. Audiometric analysis may be necessary to
assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic
class) may also cause ototoxicity, and the administration of this class of antibiotics in
patients receiving cisplatin is generally avoided. The ototoxicity of both the
aminoglycosides and cisplatin may be related to their ability to bind to melanin in the
stria vascularis of the inner ear or the generation of reactive oxygen species.
 Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and
hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium
secondary to cisplatin, so it is not primarily due to the Cisplatin.

Mode of action
Methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates
in the tetrahydrofolate synthesis.[5] The affinity of methotrexate for DHFR is about one thousand-
fold that of folate for DHFR. Dihydrofolate reductase catalyses the conversion of dihydrofolate
to the active tetrahydrofolate. Folic acid is needed for the de novo synthesis of the nucleoside
thymidine, required for DNA synthesis. Also, folate is needed for purine base synthesis, so all
purine synthesis will be inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA,
thymidylates, and proteins
Methotrexate acts specifically during DNA and RNA synthesis, and thus it is cytotoxic during
the S-phase of the cell cycle. Logically, it therefore has a greater toxic effect on rapidly dividing
cells (such as malignant and myeloid cells, and GI & oral mucosa), which replicate their DNA
more frequently, and thus inhibits the growth and proliferation of these non-cancerous cells as
well as causing the side effects listed below.
Lower doses of methotrexate have been shown to be very effective for the management of
rheumatoid arthritis, Crohn's disease, and psoriasis. For the treatment of rheumatoid arthritis,
patients should supplement their diet with folate. In these cases inhibition of dihydrofolate
reductase (DHFR) is not thought to be the main mechanism, but rather the inhibition of enzymes
involved in purine metabolism, leading to accumulation of adenosine, or the inhibition of T cell
activation and suppression of intercellular adhesion molecule expression by T cells.
Adverse effects
Possible side effects can include anemia, neutropenia, increased risk of bruising, hair loss,
nausea and vomiting, dermatitis and diarrhea. A small percentage of patients develop hepatitis,
and there is an increased risk of pulmonary fibrosis where dry cough can be an important sign.
The higher doses of methotrexate often used in cancer chemotherapy can cause toxic effects to
the rapidly-dividing cells of bone marrow and gastrointestinal mucosa. The resulting
myelosuppression and mucositis are often prevented (termed Leucovorin "rescue"- as this is the
folic acid based drug used).
Methotrexate is a highly teratogenic drug and categorized in Pregnancy Category X by the FDA.
Women must not take the drug during pregnancy, if there is a risk of becoming pregnant, or if
they are breastfeeding. Men who are trying to get their partner pregnant must also not take the
drug. To engage in any of these activities (after discontinuing the drug), women must wait until
the end of a full ovulation cycle and men must wait three months.
Reports of central nervous system reactions to methotrexate especially when given via the
intrathecal route which include myelopathies and leucoencephalopathies. It has a variety of
cutaneous side effects, in particular when administered in high doses.[9]
Generally, the more "non-specific" action a pharmacological substance has, the more possible
side effects can be expected. Methotrexate has like all "cell toxic" substances a broad array of
possible adverse effects. Care should always be taken to read the manufacturer's original
instructions for the preparation in question.
Here is a more thorough list of potential side effects for Methotrexate:
Most frequent
Ulcerative stomatitis, leukopenia, nausea, abdominal distress.

Mechanism of action
Paclitaxel interferes with the normal function of microtubule breakdown. Whereas drugs like
colchicine prevent microtubular polymerization (by binding tubulin subunits), paclitaxel arrests
their function by having the opposite effect; it hyperstabilizes their structure. This destroys the
cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β
subunit of tubulin. Tubulin is the "building block" of microtubules, and the binding of paclitaxel
locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have
the ability to disassemble. This adversely affects cell function because the shortening and
lengthening of microtubules (termed dynamic instability) is necessary for their function as a
mechanism to transport other cellular components. For example, during mitosis, microtubules
position the chromosomes during their replication and subsequent separation into the two
daughter-cell nuclei.[31][32]
Further research has indicated paclitaxel induces programmed cell death (apoptosis) in cancer
cells by binding to an apoptosis-stopping protein called Bcl-2 (B-cell leukemia 2) and thus
arresting its function.[33]
In addition to stabilizing microtubules, paclitaxel may act as a molecular mop by sequestering
free tubulin, effectively depleting the cells' supply of tubulin monomers and/or dimers. This
activity may trigger the aforementioned apoptosis.[34]
One common characteristic of most cancer cells is their rapid rate of cell division. To
accommodate this, the cytoskeleton of a cell undergoes extensive restructuring. Paclitaxel is an
effective treatment for aggressive cancers because it adversely affects the process of cell division
by preventing this restructuring. Cancer cells are also destroyed by the aforementioned anti-Bcl-
2 mechanism. Other cells are also affected adversely, but since cancer cells divide much faster
than noncancerous cells, they are far more susceptible to paclitaxel treatment.
Side effects
Common side effects include nausea and vomiting, loss of appetite, change in taste, thinned or
brittle hair, pain in the joints of the arms or legs lasting 2–3 days, changes in the color of the
nails,and tingling in the hands or toes. More serious side effects such as unusual bruising or
bleeding, pain/redness/swelling at the injection site, change in normal bowel habits for more than
2 days, fever, chills, cough, sore throat, difficulty swallowing, dizziness, shortness of breath,
severe exhaustion, skin rash, facial flushing, female infertility by ovarian damage[42] and chest
pain can also occur. A number of these side effects are associated with the excipient used,
Cremophor EL, a polyoxyethylated castor oil. Allergies to drugs such as cyclosporine, teniposide
and drugs containing polyoxyethylated castor oil may indicate increased risk of adverse reactions
to paclitaxel.[43] Dexamethasone is given prior to beginning paclitaxel treatment to mitigate some
of the side effects. Leuprolide, a GnRH analog may prevent ovarian damage, according to mice
studies