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Drug Mechanism of Action Indication Adverse Effects

Procarbazine (Matulane) Activated in the liver by CYP450 enzymes to Component of combination therapy Leukopenia, Thrombocytopenia
o Methylhydrazine class reactive azoxy compounds azoprocarbazine, (and for Hodgkin’s disease and brain Nausea and vomiting
H2O2) that alkylate DNA. In addition, it methylates tumours.
DNA & inhibits DNA & protein synthesis. Note: Avoid taking the drug with
o Its metabolites has a weak MAOI activity* alcohol, MAOIs & tyramine-rich foods.*
Dacarbazine Must undergo biotransformation to an active Treatment of malignant melanoma, Myelosupression
o Triazenes class metabolite, methyltriazenoimidazole carboxamide Hodgkin’s lymphoma, soft tissue Nausea and vomiting
(MTIC). This metabolite is responsible for the drug’s sarcomas, and neuroblastoma. Flu-like symptoms
activity as an alkylating agent by forming
methylcarbonium ions that can attack the Less common: alopecia, neurotoxicity,
nucleophilic groups in the DNA molecule. hepatotoxicity, facial flushing
Bendamustine (Treandar) Displays a unique pattern of cytotoxicity compared Treatment of CLL (chronic lympholytic Myelosuppresion
o Nitrogen Mustard class with conventional alkylating agents. The alkylating leukemia), non-Hodgkin’s lymphoma. Nausea and vomiting
agent properties are similar to those seen with Mucositis
cyclophosphamide, chlorambucil, and melphalan,
and the benzimidazole ring is similar to cladribine.

Methotrexate (Trexall) MTX is structurally related to folic acid and acts as Treatment of breast cancer, head Mucositis, diarrhea, myelosuppression
an antagonist of the vitamin by inhibiting and neck cancer, osteogenic with neutropenia & thrombocytopenia
mammalian dihydrofolate reductase (DHFR), the sarcoma, primary central nervous N/V/D, stomatitis, rash, alopecia,
enzyme that converts folic acid to its active, system lymphoma, non-Hodgkin’s o High-dose: Renal damage
coenzyme form, tetrahydrofolic acid (FH4) needed lymphoma, bladder cancer and, IT: neurologic toxicities
for DNA synthesis. choriocarcinoma.
Leucovorin is administered to undue
MTX also: In addition, low-dose MTX is effective untoward cell toxicity of MTX
o Inhibits thymidine synthase; as a single agent against certain
o Inhibits de novo purine nucleotide synthesis inflammatory diseases, such as severe Drug Interactions:
psoriasis and rheumatoid arthritis, as Omeprazole, folic acid, warfarin,
MTX is specific for the S-phase of the cell cycle. well as Crohn disease. NSAIDs, penicillins, cephalosporins
Pemetrexed (Alimta) Similar to Methotrexate Treatment of mesothelioma, non- Myelosuppression, skin rash, mucositis,
o Inhibits mammalian DHFR small cell lung cancer (NSCLC). diarrhea, fatigue, hand-foot syndrome
o Inhibits thymidine synthase (main action) o Dexamethasone is administered
o Inhibits de novo purine nucleotide synthesis to prevent painful erythema.
o Vitamin B12 appears to reduce
toxicity while not interfering clinical
efficacy
Pralatrexate (Folotyn) Similar to Methotrexate and Pemetrexed Treatment of NSCLC, relapsed or Myelosuppression, skin rash, mucositis,
o Inhibits mammalian DHFR refractory peripheral T-cell lymphoma. diarrhea, and fatigue.
o Inhibits thymidine synthase (main action) o Vitamin B12 appears to reduce
o Inhibits de novo purine nucleotide synthesis toxicity while not interfering clinical
efficacy
5-Fluorouracil (Adrucil) o Inhibits thymidine synthase (main action) Treatment of colorectal cancer, anal Nausea, mucositis, diarrhea, bone
o Fluoropyrimidines class o Incorporation of FUTP into RNA cancer, breast cancer, head and marrow depression, neurotoxicity
o Alteration in RNA processing neck cancer, gastroesophageal
o Incorporation of FdUTP into DNA cancer, and hepatocellular cancer.
o Inhibition of DNA synthesis & function Superficial basal carcinoma – topical

DAYRIT JAMES S | BS Pharmacy 4-2


Capecitabine (Xeloda) After absorption, capecitabine itself is non-toxic, Treatment of colorectal cancer, Nausea, vomiting, diarrhea, mucositis,
undergoes a series of enzymatic reaction, last of breast cancer, gastroesophageal myelosuppression, chest pain, “hand-
which is hydrolysis to 5-FU. cancer, hepatocellular cancer, foot syndrome”
o Hence, capecitabine and 5-FU has same pancreatic cancer.
cytotoxic activity and tumor specificity.
Cytarabine (Ara-C) o Ara-CTP triphosphate – the main cytotoxic Acute myeloid leukemia (AML), acute Nausea and vomiting, conjunctivitis,
o Deoxycytidine analogs metabolite that inhibits DNA polymerases. lymphoid lekumia (ALL), chronic cerebellar ataxia, myelosuppression
o Inhibits DNA chain elongation, synthesis & repair myeloid leukemia (CML) in blast crisis with neutropenia, hepatotoxic, and
o Inhibits ribonucleotide reductase with reduced thrombocytopenia.
formation of dNTPs; Inactive in solid tumors
o Incorporation of cytarabine triphosphate into
DNA. Cytarabine is S-phase (cell cycle) specific.
Gemcitabine (Gemzar) o Inhibits DNA synthesis and repair; Treatment of pancreatic cancer, Nausea, vomiting, diarrhea, alopecia,
o Inhibits ribonucleotide reductase with reduced bladder cancer, breast cancer, non- flu-like symptoms, myelosuppression.
formation of dNTPs small cell lung cancer, ovarian
o Incorporation of gemcitabine triphosphate into cancer, non-Hodgkin’s lymphoma,
DNA resulting in inhibition of DNA synthesis and soft tissue sarcoma
function
6-Mercaptopurine (6-MP) o Inhibits de novo purine nucleotide synthesis; Maintenance of remission in acute Nausea, vomiting, myelosuppression,
(Purinethol) o Incorporation of triphosphate into RNA lymphoblastic leukemia. immunosuppression, &hepatotoxicity
o 6-Thiopurines class o Incorporation of triphosphate into DNA
o TIMP (6-thioinosinic acid)– cytotoxic metabolite
Fludarabine (Fludara) o Inhibits DNA synthesis and repair Treatment of chronic lymphocytic Myelosuppression, immunosuppression,
o Inhibits ribonucleotide reductase leukemia, hairy cell leukemia, and nausea and vomiting, fever, myalgias,
o Induction of apoptosis indolent non-Hodgkin lymphoma arthralgias
o Incorporation of fludarabine triphosphate into
DNA (and RNA). Note: Risk of opportunistic infections
Cladribine (Leustatin) o Inhibits DNA synthesis and repair Treatment of hairy cell leukemia, Myelosuppression, immunosuppression,
o Inhibits ribonucleotide reductase chronic lymphocytic leukemia (CLL) nausea and vomiting
o Induction of apoptosis and non-Hodgkin lymphoma
o Incorporation of cladribine triphosphate into
DNA (and RNA).
Vinblastine Vincristine (VX), vinorelbine (VRB), and inblastine Treatment of Hodgkin’s and non- Acute: Nausea and vomiting
(VBL) are all cell cycle specific and phase specific, Hodgkin’s lymphoma, germ cell Delayed: Myelosuppression, mucositis,
because they block mitosis in metaphase (M- cancer, breast cancer, Kaposi’s alopecia, & syndrome of inappropriate
phase) – Inhibits mitosis sarcoma secretion of antidiuretic hormone
(SIADH), vascular events.
Vinorelbine (Navelbine) Vincristine (VX), vinorelbine (VRB), and inblastine Treatment of non-small cell lung Myelosuppression, constipation, SIADH,
(VBL) are all cell cycle specific and phase specific, cancer, breast cancer, ovarian nausea and vomiting, alopecia,
because they block mitosis in metaphase (M- cancer diarrhea, alopecia
phase) – Inhibits mitosis Note: Should not inject intrathecally!
Etoposide It blocks cells in the late S- to G2 phase of the cell Treatment of non-small cell and small Acute: Nausea and vomiting
(Toposar, Vepesid) cycle. Its major target is topoisomerase II, which it cell lung cancer; non-Hodgkin’s Delayed: Alopecia, myelosuppression
inhibits function. lymphoma, gastric cancer
Topotecan Topotecan is an S-phase specific, and inhibit Treatment of small cell lung cancer, Myelosuppression, nausea & vomiting
o Camptothecins class topoisomerase I, which is essential for the replication ovarian cancer
of DNA in human cells.

DAYRIT JAMES S | BS Pharmacy 4-2


Irinotecan SN-38 (the active metabolite of irinotecan) is Treatment of colorectal cancer, Diarrhea, myelosuppression, nausea
o Camptothecins class approximately 1000 times as potent as irinotecan as gastroesophageal cancer, non-small and vomiting
an inhibitor of topoisomerase I. The topoisomerases cell and small cell lung cancer
relieve torsional strain in DNA by causing reversible,
single-strand breaks.
Mitomycin (Camptosar) Acts as an alkylating agent and forms cross-links Treatment of superficial bladder Acute: Nausea and vomiting
with DNA; formation of oxygen free radicals, which cancer, gastric cancer, breast Delayed: Myelosuppression, mucositis,
target DNA inhibiting DNA synthesis. cancer, non-small cell lung cancer, anorexia and fatigue, hemolytic-
head and neck cancer (in uremic syndrome
combination with radiotherapy)
Bleomycin (Blenoxane) Oxygen free radicals bind to DNA causing single- Treatment of Hodgkin’s and non- Pulmonary brosis, alopecia, skin
and double-strand DNA breaks Hodgkin’s lymphoma, germ cell reactions, hyperpigmentation of
cancer, head and neck cancer hands, fever, chills, anaphylaxis
Cetuximab (Erbitux) o Binds to EGFR (epidermal growth factor Treatment of colorectal cancer, head Skin rash, hypomagnesemia, fatigue,
receptor) & inhibits downstream EGFR signaling and neck cancer (used in interstitial lung disease (more ADR)
o Enhances response to chemotherapy and combination with radiotherapy),
radiotherapy non-small cell lung cancer
Panitumumab Same as Cetuximab Treatment of colorectal answer Skin rash, hypomagnesemia, fatigue,
interstitial lung disease (more ADR)
Erlotinib (Tarceva) Inhibits EGFR tyrosine kinase leading to inhibition of Treatment of non-small cell lung Diarrhea, nausea, acne-like skin rashes,
EGFR signaling –inhibition of tyrosine kinase enzyme cancer, pancreatic cancer and ocular disorders
Rituximab (Rituxan) The Fab domain of rituximab binds to the CD20 Treatment of lymphomas, chronic Anemia, neutropenia, hypotension,
antigen on the B lymphocytes, and its Fc domain lymphocytic leukemia, rheumatoid rash, gastrointestinal disturbance,
recruits immune effector functions, inducing arthritis fever, and fatigue.
complement and antibodydependent, cell-
mediated cytotoxicity of the B cells.

Mechanism: Inhibition of tyrosine kinase enzyme


Ipilimumab (Yervoy) 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)
Temozolomide (Temodar) Related to dacarbazine, because both must Treatment of glioblastomas , Myelosuppression, headache, nausea
o Triazenes class 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