Cytotoxic drugs, also known as antineoplastics, are a group of medicines used to treat cancer by preventing the replication or growth of cells. They work by damaging the cell's DNA. Combination chemotherapy using two or more agents leads to improved outcomes. Chemotherapy may be used alone or with other modalities like radiation and surgery. Alkylating agents are a major class of cytotoxic drugs that work by cross-linking DNA strands or causing DNA breaks. They are used to treat many cancer types and come in classes like nitrogen mustards, alkyl sulfonates, triazines, and ethylenimines. Adverse effects include bone marrow suppression and gastrointestinal issues.

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CYTOTOXIC DRUGS

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CYTOTOXIC DRUG
• (sometimes known as antineoplastics) describe a group of medicines that contain
chemicals which are toxic to cells, preventing their replication or growth, and so are
used to treat cancer.
• Combination therapy – the use of two or more chemotherapy agents to treat
cancer – was adopted and led to improved response rates and increased survival
times.
• Chemotherapy is used as the only treatment of cancer, or it may used in
conjunction with other modalities such as radiation, surgery, and biologic response
modifiers (BRMs).

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ALKYLATING
DRUGS

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Alkylating Drugs
● One of the largest groups of anticancer drugs.
● It damage the cell’s DNA by cross-linkage of DNA strands,
abnormal base pairing, or DNA strand breaks, thus
preventing the reproduction of cancer cells.
● They are used to treat many different types of cancer
including leukemia, lymphoma, multiple myeloma,
sarcoma, and solid tumors such as those of the breast,
ovary, uterus, lung, bladder, and stomach.

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5 CLASSES
OF
ALKYLATING
DRUGS

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Nitrogen
Mustards
Alkyl
Sulfonate
s
5 classes of Alkylating Drugs
Nitrosoureas
Triazines Ethylenimines

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General Adverse Reactions
Adverse Reactions
Bone Marrow Suppression/ Myelosuppression
Low RBC count (anemia)
Low WBC count (leukopenia)
Low platelet count (thrombocytopenia)
Gastrointestinal Disturbances
Anorexia
Nausea and vomiting
Diarrhea
Mucositis (stomatitis)
Other
Alopecia
Fatigue
infertility

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NITROGEN MUSTARDS

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Nitrogen Mustards
● it is not found naturally in the environment
● HN-1 originally was designed to remove warts
but later on, it was identified as a potential
chemical warfare agent.
● HN-2 was designed for military agent but was
later used in cancer treatment.

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MECHLORETHAMINE
The first clinically used nitrogen mustard and is
the most reactive of the drugs in this class. It is
used topically for treatment of CTCL as a
solution that is rapidly mixed and applied to
affected areas. It has been largely replaced by
cyclophosphamide, melphalan, and other more
stable alkylating agents.

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MECHLORETAMINE
ROUTE AND DOSAGE USES AND CONSIDERATIONS
HODGKIN DISEASE:
A: IV: 0.2 mg/kg or 6 mg/m2 as single dose FOR HODGKIN DISEASE, LEUKEMIAS, SOLID
TUMORS AND EFFUSION CAUSED BY
CANCER. This drug is contraindicated in patients
with active infections
• PB: 94% - 96 %
• t½: 40 min
CLL:
A: IV: 6 mg/m2 q4wk
CML:
A: IV: 0.4 mg/kg or 6 mg/m2 monthly
Other dosing regimen and routes are available

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CYCLOPHOSPHAMINE
• An analogue of nitrogen mustard and has activity
against many neoplastic diseases such as Hodgkin and
non-Hodgkin lymphoma (NHL), acute and chronic
lymphocytic leukemia (CLL) and etc.
• Used for immunologic disorders such as lupus
nephritis, and has been shown to prevent progressive
renal scarring, preserve renal function, induce renal
remission and decrease end-stage renal failure.

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CYCLOPHOSPHAMIDE (Cont.)
• This drug is a severe vesicant, that causes tissue necrosis if it infiltrates
into the tissues.
• Given orally or intravenously
• A prodrug that is activated and extensively metabolized by the liver.
• 5% or 25% of the drug is eliminated by the kidney as unchanged, and its
elimination half life is 3-12 hours.
• Patients should report all medications they are taking, including over-the-
counter (OTC) medicines and herbal supplements.
• Patient should be hydrated while taking the drug to prevent hemorrhagic
cystitis

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Sodium 2- mercaptoethanesulfonate
A chemoprotectant drug often given
with high-dose cyclophosphamide to
inactivate urotoxic metabolites to
reduce the incidence of hemorrhagic
cystitis.

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• almost exclusively used in treating CLL
• The cytotoxic effects of chlorambucil on the bone
marrow, lymphoid organs, and epithelial tissues are
similar to those observed with other nitrogen mustards.
As an orally administered agent, chlorambucil is well
tolerated in small daily doses and provides flexible
titration of blood counts. Nausea and vomiting may
result from single oral doses of 20 mg or greater.
CHLORAMBUCIL

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CHLORAMBUCIL
ROUTE AND DOSAGE USES AND CONSIDERATIONS
Palliative CLL, Hodgkin Disease, and NHL:
A: PO: 0.1-0.2 mg/kg/d (4-10 mg/d) for 3-6 weeks
FOR CLL AND NHL:
• Monitor for bone marrow suppression or
pancytopenia
• PB: 99 %
• t½: 1.5 h

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IFOSFAMIDE
● Ifosfamide is an analogue of cyclophosphamide.
● Ifosfamide is approved for treatment of patients with
relapsed germ cell testicular cancer and is frequently
used for first-time treatment of pediatric or adult
patients with sarcomas
● It is a common component of high dose
chemotherapy regimens with bone marrow or stem
cell rescue

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IFOSFAMIDE
ROUTE AND DOSAGE USES AND CONSIDERATIONS
A: IV: 1.2-2g/m2/d for 5 d in combination with
MESNA; repeat every 3 wk after recovery from
hematologic toxicity. Mesna is usually given
concomitantly to prevent hemorrhagic cystitis
FOR TESTICULAR CANCER:
• Monitor for hemorrhagic cystitis
• PB: negligible
• t½: 7-15 h

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BENDAMUSTINE
● approved for treatment of CLL and non-Hodgkin
lymphoma.
● rapidly degraded through sulfhydryl interaction
and adduct formation with macromolecules; less
than 5% of the parent drug is excreted in the urine
intact
● The parent drug has a plasma t 1/2 of about 30 min.

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BENDAMUSTINE
ROUTE AND DOSAGE USES AND CONSIDERATIONS
CLL:
A: IV: 100 mg/m2 on days 1 and 2, repeated q28d
for up to 6 cycles
FOR CLL AND NHL:
• Monitor for bone marrow depression
• Assess for tumor lysis syndrome and skin
reactions
• PB: 94% - 96 %
• t½: 40 min
NHL:
A: IV: 120 mg/m2 on days 1 and 2, repeated q21d
for up to 8 cycles

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MELPHALAN
● used to treat multiple myeloma and, less commonly, in
high-dose chemotherapy with bone marrow
transplantation. The general pharmacological and
cytotoxic actions of melphalan are similar to those of
other bifunctional alkylators. The drug is not a vesicant.
● may be used in myeloablative regimens followed by
bone marrow or peripheral blood stem cell
reconstitution

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MELPHALAN
ROUTE AND DOSAGE USES AND CONSIDERATIONS
MULTIPLE MYELOMA:
A: PO: 6 mg daily for 2-3 wks; maint; 2 mg/d;
adjust 1-3 mg/d based on hematologic response
A: IV: 16 mg/m2 q2wk for 8 doses; maint; 16
mg/m2 q4wk
FOR MULTIPLE MYELOMA AND OVARIAN
CANCER:
• Do not confuse with alkeran with Leukeran or
Myleran
• PB: 20% -30 %
• t½: 1.25- 1.5 h
OVARIAN CANCER:
A: PO: 200 mcg/kg/d for 5 d; repeat q4-5wk based
on hematologic response

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ESTRAMUSTINE
ROUTE AND DOSAGE USES AND CONSIDERATIONS
A: PO: 14 mg/kg/d or 600 mg /m2/d in 3-4 divided
doses
FOR PALLIATIVE TREATMENT OF PROSTATE
CANCER.
• Gynecomastia and impotence may occur
• PB: UK
• t½: 20-24 h

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NITROSOUREAS

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Nitrosoureas
● Have an important role in the treatment of brain tumors and
find occasional use in treating lymphomas and in high-dose
regimens with bone marrow reconstitution. They function as
bifunctional alkylating agents but differ from conventional
nitrogen mustards in both pharmacological and
toxicological properties.
● Cross-blood barrier, making them useful in the treatment of
brain cancer.

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CARMUSTINE (BCNU)
● its ability to cross the blood-brain barrier, an
important property in the treatment of brain
tumors.
● used in the treatment of malignant gliomas. An
implantable carmustine wafer is available for use
as an adjunct to surgery for recurrent
glioblastoma multiforme

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CARMUSTINE (BCNU)
ROUTE AND DOSAGE USES AND CONSIDERATIONS
A: IV: 150-200 mg/m2 single dose q6wk or 75-100
mg/m2/d for 2 days q6wk
FOR HODGKIN DISEASE, NHL, MULTIPLE
MYELOMA, AND BRAIN TUMORS.
• Monitor for bone marrow suppression and
pulmonary symptoms
• PB: UK
• t½: 5-30 mins

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STREPTOZOCIN
● used in the treatment of human pancreatic
islet cell carcinoma and carcinoid tumors.
● has a methylnitrosourea moiety attached to
the 2-carbon of glucose. It has a high affinity
for cells of the islets of Langerhans and
causes diabetes in experimental animals.

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STREPTOZOCIN
ROUTE AND DOSAGE USES AND CONSIDERATIONS
A: IV: 500 mg/m2/d for 5 d q4-6 wk;
doses above 500 mg/m2 are not recommended
FOR PANCREATIC CANCER.
• Do not confuse with streptomycin
• PB: UK
• t½:30-45 mins

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LOMUSTINE (CCNU)
ROUTE AND DOSAGE USES AND CONSIDERATIONS
FOR HODGKIN DISEASE AND MALIGNANT
GLIOMA:
A:PO: 100-130 mg/m2 q6wk
FOR HODGKIN DISEASE AND MALIGNANT
GLIOMA.
• Monitor for bone marrow suppression and liver
function
• PB: UK
• t½: 16 h – 2 d

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ALKYL SULFONATES

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BUSULFAN
● the initial oral dose of busulfan varies with the
total leukocyte count and the severity of the
disease
● primarily used in high-dose regimens, in which
pulmonary fibrosis, GI mucosal damage, and
hepatic VOD are important toxicities.

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BUSULFAN
ROUTE AND DOSAGE USES AND CONSIDERATIONS
A: PO: 4-8 mg/d
FOR MYELOCYTIC CANCER
• Monitor for seizures and cerebral hemorrhage
• PB: 32%
• t½: 2.5 h

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TRIAZINES

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DACARBAZINE (DTIC)
● a methylating agent after metabolic activation to the
monomethyl triazeno metabolite MTIC. It kills cells in all
phases of the cell cycle. Resistance has been ascribed to
the removal of methyl groups from the O6-guanine bases
in DNA by MGMT.
● The primary clinical indication for dacarbazine is in the
chemotherapy of Hodgkin disease

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DACARBAZINE (DTIC)
ROUTE AND DOSAGE USES AND CONSIDERATIONS
MELANOMA:
A: IV: 250 mg/m2/d for 5 d; repeat q3wk for 2
more cycles
FOR HODGKIN DISEASE AND MALIGNANT
MELANOMA:
• Monitor hepatic function
• PB: minimal
• t½: 5 h
HODGKIN DISEASE:
A: IV: 375 mg/m2 on day 1 q2wk for 12 cycles

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ETHYLENIMINES

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ALTRETAMINE
● Its precise mechanism of cytotoxicity is unknown,
although it can alkylate DNA and proteins.
● It is a palliative treatment of patients with
persistent or recurrent ovarian cancer following
cisplatin-based combination therapy
● The drug undergoes rapid demethylation in the
liver

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ALTRETAMINE
ROUTE AND DOSAGE USES AND CONSIDERATIONS
A: PO: 260 mg/m2/d on 4 divided doses after
meals and at bedtime for 14-21 d in 28-d cycles;
Drug holiday for > 14 d then restart at 200
mg/m2/d
FOR OVARIAN CANCER:
• PB: weakly
• t½: 4.7-10.2 h

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PLATINUM
COORDINATION
COMPLEXES

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PLATINUM COORDINATION COMPLEXES
• Platinum coordination complexes have broad
antineoplastic activity and have become the
foundation for treatment of ovarian, head and neck,
bladder, esophagus, lung, and colon cancers
• Although cisplatin and other platinum complexes do
not form carbonium ion intermediates like other
alkylating agents or formally alkylate DNA, they
covalently bind to nucleophilic sites on DNA and share
many pharmacological attributes with alkylators

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CISPLATIN
Cisplatin is used to treat various
types of cancer. It is a chemotherapy
drug that contains platinum. It is used
to slow or stop cancer cell growth.

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CISPLATIN (cont.)
• Cisplatin, in combination with bleomycin, etoposide, or with
ifosfamide and vinblastine, cures 90% of patients with
testicular cancer. Used with paclitaxel, cisplatin or
carboplatin induces complete response in the majority of
patients with carcinoma of the ovary. Cisplatin produces
responses in cancers of the bladder, head and neck, cervix,
and endometrium; all forms of carcinoma of the lung; anal
and rectal carcinomas; and neoplasms of childhood.
• The drug also sensitizes cells to radiation therapy and
enhances control of locally advanced lung, esophageal, and
head and neck tumors when given with irradiation.

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CISPLATIN
ROUTE AND DOSAGE USES AND CONSIDERATION
BLADDER CANCER
A: IV: 50-70 mg/m2 q3-4wk
FOR BLADDER, OVARIAN AND NSCLC.
• Monitor for CNS function
• Reversible posterior leukoencephalopathy
may occur
• PB: 90 %
• t½: 30-100 h, dose related
OVARIAN CANCER
A: IV: 50-75 mg/m2 q21d
TESTICULAR CANCER
A: IV: 20 mg/m2 for 5d; repeat q3wk for 2
more cycles

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CARBOPLATIN
carboplatin is much less reactive than
cisplatin, the majority of drug in plasma
remains in its parent form, unbound to
proteins. Most drug is eliminated via renal
excretion

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CARBOPLATIN (cont.)
• Carboplatin and cisplatin are equally effective in the treatment of
patients with suboptimally debulked ovarian cancer, non–small cell lung
cancer, and extensive-stage small cell lung cancer; however, carboplatin
may be less effective than cisplatin in the treatment of patients with
germ cell, head and neck, and esophageal cancers.
• Carboplatin is an effective alternative for responsive tumors in patients
unable to tolerate cisplatin because of impaired renal function, refractory
nausea, significant hearing impairment, or neuropathy, but doses must be
adjusted for renal function.
• may be used in high-dose therapy with bone marrow or peripheral stem
cell rescue

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CARBOPLATIN
ROUTE AND DOSAGE USES AND CONSIDERATION
NEW CANCER
A: IV: 300 mg/m2 in combination with
cyclophosphamide q4wk for 6 cycles
FOR ADVANCED OVARIAN CANCER.
• Usually given as combination therapy
• PB: UK
• t½: 1.5-2.5 H
RECURRENT CANCER
A: IV: 360 mg/m2 q4wk

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OXALIPLATIN
● has a short t½ in plasma, probably as a result of its
rapid uptake by tissues and its reactivity
● exhibits a range of antitumor activity (colorectal
and gastric cancer) that differs from other
platinum agents.
● Oxaliplatin’s effectiveness in colorectal cancer is
perhaps due to its MMR- and HMG-independent
effects.

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OXALIPLATIN
ROUTE AND DOSAGE USES AND CONSIDERATION
A: IV: 85 mg/m2 on day 1 q2wk for 12 cycles
FOR METASTIC COLORECTAL CANCER.
• Used with 5-FU (fluorouracil) and leucovorin
(FOLFOX4)
• Assess for pulmonary complication
• PB: >90%
• t½: 391 h

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