Drug
Procarbazine (Matulane)
o Methylhydrazine class
Dacarbazine
o Triazenes class
Bendamustine (Treandar)
o Nitrogen Mustard class
Methotrexate (Trexall)
Pemetrexed (Alimta)
Pralatrexate (Folotyn)
5-Fluorouracil (Adrucil)
o Fluoropyrimidines class
DAYRIT JAMES S | BS Pharmacy 4-2
Mechanism of Action
Activated in the liver by CYP450 enzymes to
reactive azoxy compounds azoprocarbazine, (and
H2O2) that alkylate DNA. In addition, it methylates
DNA & inhibits DNA & protein synthesis.
o Its metabolites has a weak MAOI activity*
Must undergo biotransformation to an active
metabolite, methyltriazenoimidazole carboxamide
(MTIC). This metabolite is responsible for the drug’s
activity as an alkylating agent by forming
methylcarbonium ions that can attack the
nucleophilic groups in the DNA molecule.
Displays a unique pattern of cytotoxicity compared
with conventional alkylating agents. The alkylating
agent properties are similar to those seen with
cyclophosphamide, chlorambucil, and melphalan,
and the benzimidazole ring is similar to cladribine.
MTX is structurally related to folic acid and acts as
an antagonist of the vitamin by inhibiting
mammalian dihydrofolate reductase (DHFR), the
enzyme that converts folic acid to its active,
coenzyme form, tetrahydrofolic acid (FH4) needed
for DNA synthesis.
MTX also:
o Inhibits thymidine synthase;
o Inhibits de novo purine nucleotide synthesis
MTX is specific for the S-phase of the cell cycle.
Similar to Methotrexate
o Inhibits mammalian DHFR
o Inhibits thymidine synthase (main action)
o Inhibits de novo purine nucleotide synthesis
Similar to Methotrexate and Pemetrexed
o Inhibits mammalian DHFR
o Inhibits thymidine synthase (main action)
o Inhibits de novo purine nucleotide synthesis
o Inhibits thymidine synthase (main action)
o Incorporation of FUTP into RNA
o Alteration in RNA processing
o Incorporation of FdUTP into DNA
o Inhibition of DNA synthesis & function
Indication
Component of combination therapy
for Hodgkin’s disease and brain
tumours.
Treatment of malignant melanoma,
Hodgkin’s lymphoma, soft tissue
sarcomas, and neuroblastoma.
Treatment of CLL (chronic lympholytic
leukemia), non-Hodgkin’s lymphoma.
Treatment of breast cancer, head
and neck cancer, osteogenic
sarcoma, primary central nervous
system lymphoma, non-Hodgkin’s
lymphoma, bladder cancer and,
choriocarcinoma.
In addition, low-dose MTX is effective
as a single agent against certain
inflammatory diseases, such as severe
psoriasis and rheumatoid arthritis, as
well as Crohn disease.
Treatment of mesothelioma, non-
small cell lung cancer (NSCLC).
Treatment of NSCLC, relapsed or
refractory peripheral T-cell lymphoma.
Treatment of colorectal cancer, anal
cancer, breast cancer, head and
neck cancer, gastroesophageal
cancer, and hepatocellular cancer.
Superficial basal carcinoma – topical
Adverse Effects
Leukopenia, Thrombocytopenia
Nausea and vomiting
Note: Avoid taking the drug with
alcohol, MAOIs & tyramine-rich foods.*
Myelosupression
Nausea and vomiting
Flu-like symptoms
Less common: alopecia, neurotoxicity,
hepatotoxicity, facial flushing
Myelosuppresion
Nausea and vomiting
Mucositis
Mucositis, diarrhea, myelosuppression
with neutropenia & thrombocytopenia
N/V/D, stomatitis, rash, alopecia,
o High-dose: Renal damage
IT: neurologic toxicities
Leucovorin is administered to undue
untoward cell toxicity of MTX
Drug Interactions:
Omeprazole, folic acid, warfarin,
NSAIDs, penicillins, cephalosporins
Myelosuppression, skin rash, mucositis,
diarrhea, fatigue, hand-foot syndrome
o Dexamethasone is administered
to prevent painful erythema.
o Vitamin B12 appears to reduce
toxicity while not interfering clinical
efficacy
Myelosuppression, skin rash, mucositis,
diarrhea, and fatigue.
o Vitamin B12 appears to reduce
toxicity while not interfering clinical
efficacy
Nausea, mucositis, diarrhea, bone
marrow depression, neurotoxicity
 Capecitabine (Xeloda)
Cytarabine (Ara-C)
o Deoxycytidine analogs
Gemcitabine (Gemzar)
6-Mercaptopurine (6-MP)
(Purinethol)
o 6-Thiopurines class
Fludarabine (Fludara)
Cladribine (Leustatin)
Vinblastine
Vinorelbine (Navelbine)
Etoposide
(Toposar, Vepesid)
Topotecan
o Camptothecins class
DAYRIT JAMES S | BS Pharmacy 4-2
After absorption, capecitabine itself is non-toxic,
undergoes a series of enzymatic reaction, last of
which is hydrolysis to 5-FU.
o Hence, capecitabine and 5-FU has same
cytotoxic activity and tumor specificity.
o Ara-CTP triphosphate – the main cytotoxic
metabolite that inhibits DNA polymerases.
o Inhibits DNA chain elongation, synthesis & repair
o Inhibits ribonucleotide reductase with reduced
formation of dNTPs;
o Incorporation of cytarabine triphosphate into
DNA. Cytarabine is S-phase (cell cycle) specific.
o Inhibits DNA synthesis and repair;
o Inhibits ribonucleotide reductase with reduced
formation of dNTPs
o Incorporation of gemcitabine triphosphate into
DNA resulting in inhibition of DNA synthesis and
function
o Inhibits de novo purine nucleotide synthesis;
o Incorporation of triphosphate into RNA
o Incorporation of triphosphate into DNA
o TIMP (6-thioinosinic acid)– cytotoxic metabolite
o Inhibits DNA synthesis and repair
o Inhibits ribonucleotide reductase
o Induction of apoptosis
o Incorporation of fludarabine triphosphate into
DNA (and RNA).
o Inhibits DNA synthesis and repair
o Inhibits ribonucleotide reductase
o Induction of apoptosis
o Incorporation of cladribine triphosphate into
DNA (and RNA).
Vincristine (VX), vinorelbine (VRB), and inblastine
(VBL) are all cell cycle specific and phase specific,
because they block mitosis in metaphase (M-
phase) – Inhibits mitosis
Vincristine (VX), vinorelbine (VRB), and inblastine
(VBL) are all cell cycle specific and phase specific,
because they block mitosis in metaphase (M-
phase) – Inhibits mitosis
It blocks cells in the late S- to G2 phase of the cell
cycle. Its major target is topoisomerase II, which it
inhibits function.
Topotecan is an S-phase specific, and inhibit
topoisomerase I, which is essential for the replication
of DNA in human cells.
Treatment of colorectal cancer,
breast cancer, gastroesophageal
cancer, hepatocellular cancer,
pancreatic cancer.
Acute myeloid leukemia (AML), acute
lymphoid lekumia (ALL), chronic
myeloid leukemia (CML) in blast crisis
Inactive in solid tumors
Treatment of pancreatic cancer,
bladder cancer, breast cancer, non-
small cell lung cancer, ovarian
cancer, non-Hodgkin’s lymphoma,
soft tissue sarcoma
Maintenance of remission in acute
lymphoblastic leukemia.
Treatment of chronic lymphocytic
leukemia, hairy cell leukemia, and
indolent non-Hodgkin lymphoma
Treatment of hairy cell leukemia,
chronic lymphocytic leukemia (CLL)
and non-Hodgkin lymphoma
Treatment of Hodgkin’s and non-
Hodgkin’s lymphoma, germ cell
cancer, breast cancer, Kaposi’s
sarcoma
Treatment of non-small cell lung
cancer, breast cancer, ovarian
cancer
Treatment of non-small cell and small
cell lung cancer; non-Hodgkin’s
lymphoma, gastric cancer
Treatment of small cell lung cancer,
ovarian cancer
Nausea, vomiting, diarrhea, mucositis,
myelosuppression, chest pain, “hand-
foot syndrome”
Nausea and vomiting, conjunctivitis,
cerebellar ataxia, myelosuppression
with neutropenia, hepatotoxic, and
thrombocytopenia.
Nausea, vomiting, diarrhea, alopecia,
flu-like symptoms, myelosuppression.
Nausea, vomiting, myelosuppression,
immunosuppression, &hepatotoxicity
Myelosuppression, immunosuppression,
nausea and vomiting, fever, myalgias,
arthralgias
Note: Risk of opportunistic infections
Myelosuppression, immunosuppression,
nausea and vomiting
Acute: Nausea and vomiting
Delayed: Myelosuppression, mucositis,
alopecia, & syndrome of inappropriate
secretion of antidiuretic hormone
(SIADH), vascular events.
Myelosuppression, constipation, SIADH,
nausea and vomiting, alopecia,
diarrhea, alopecia
Note: Should not inject intrathecally!
Acute: Nausea and vomiting
Delayed: Alopecia, myelosuppression
Myelosuppression, nausea & vomiting
 Irinotecan
o Camptothecins class
Mitomycin (Camptosar)
Bleomycin (Blenoxane)
Cetuximab (Erbitux)
Panitumumab
Erlotinib (Tarceva)
Rituximab (Rituxan)
SN-38 (the active metabolite of irinotecan) is Treatment of colorectal cancer,
approximately 1000 times as potent as irinotecan as gastroesophageal cancer, non-small
an inhibitor of topoisomerase I. The topoisomerases cell and small cell lung cancer
relieve torsional strain in DNA by causing reversible,
single-strand breaks.
Acts as an alkylating agent and forms cross-links Treatment of superficial bladder
with DNA; formation of oxygen free radicals, which cancer, gastric cancer, breast
target DNA inhibiting DNA synthesis. cancer, non-small cell lung cancer,
head and neck cancer (in
combination with radiotherapy)
Oxygen free radicals bind to DNA causing single- Treatment of Hodgkin’s and non-
and double-strand DNA breaks Hodgkin’s lymphoma, germ cell
cancer, head and neck cancer
o Binds to EGFR (epidermal growth factor Treatment of colorectal cancer, head
receptor) & inhibits downstream EGFR signaling and neck cancer (used in
o Enhances response to chemotherapy and combination with radiotherapy),
radiotherapy non-small cell lung cancer
Same as Cetuximab Treatment of colorectal answer
Inhibits EGFR tyrosine kinase leading to inhibition of Treatment of non-small cell lung
EGFR signaling –inhibition of tyrosine kinase enzyme cancer, pancreatic cancer
The Fab domain of rituximab binds to the CD20 Treatment of lymphomas, chronic
antigen on the B lymphocytes, and its Fc domain lymphocytic leukemia, rheumatoid
recruits immune effector functions, inducing arthritis
complement and antibodydependent, cell-
mediated cytotoxicity of the B cells.
Diarrhea, myelosuppression, nausea
and vomiting
Acute: Nausea and vomiting
Delayed: Myelosuppression, mucositis,
anorexia and fatigue, hemolytic-
uremic syndrome
Pulmonary brosis, alopecia, skin
reactions, hyperpigmentation of
hands, fever, chills, anaphylaxis
Skin rash, hypomagnesemia, fatigue,
interstitial lung disease (more ADR)
Skin rash, hypomagnesemia, fatigue,
interstitial lung disease (more ADR)
Diarrhea, nausea, acne-like skin rashes,
and ocular disorders
Anemia, neutropenia, hypotension,
rash, gastrointestinal disturbance,
fever, and fatigue.

Mechanism: Inhibition of tyrosine kinase enzyme

Ipilimumab (Yervoy)
Temozolomide (Temodar)
o Triazenes class
Binds to CTLA-4, blocking the inhibitory signal, which Treatment of unresectable or Enterocolitis, hepatitis, dermatitis,
allows the CTLs to destroy the cancer cells. metastatic melanoma. neuropathy, and endocrinopathy
o Blocks the inhibitory signal of dendritic cells
o CTLs (Cytotoxic T lymphocytes) can kill cancer
cells, however they are inhibited (dendritic cell)
Related to dacarbazine, because both must Treatment of glioblastomas , Myelosuppression, headache, nausea
undergo biotransformation to an active metabolite, anaplastic astrocytomas, and and vomiting, fatigue, photosensitivity
MTIC, which probably is responsible for the metastatic melanoma
methylation of DNA on the 6 position of guanine.
Unlike dacarbazine, temozolomide does not require
the CYP450 system for metabolic transformation,
and it undergoes chemical transformation at
normal physiological pH.
o Also has the property of inhibiting the repair
enzyme, O6-guanine-DNA alkyltransferase

DAYRIT JAMES S | BS Pharmacy 4-2