CANCER DRUGS

Drugs underlined are considered as core drugs, while drugs with (+) are considered complementary drugs
ANTIMETABOLITES
Folic acid Analogs “T-REX WITH A FOLEY CATHETER”
Methotrexate  MOA: competes with folic acid for sites in DHFR  inhibits DNA, RNA, protein synthesis in cancer cells
 Interferes with purine and thymidilate synthesis
 Oral or parenteral drug form
 Metabolized in the liver
 Renal excretion
 AE: Myelosuppression, N&V, diarrhea, renal failure, hepatotoxicity, mucositis, thrombocytopenia
 Uses: Acute Lymphocytic Leukemia, Choriocarcinoma, NHL, psoriasis, rheumatoid arthritis,
immunosuppression, ectopic pregnancy
Pemetrexed
Prelatrexate
Purine Analogs “Adenine & Guanine”
Mercatopurine  MOA: Converted to nucleotide form by HGPRT  incorporated into DNA instead of guanine
 Inhibits de novo purine synthesis
 Allopurinol increases Mercaptopurine levels in the body
 AE: myelosuppression, hepatotoxicity, anorexia, N&V
 Uses: Leukemias: ALL, AML, CML
Thioguanine
Pentostatin
Pyrimidine Analogs “Cytosine, Uracil, Thymine”
Fluorouracil (5-FU)  Inhibits thymidine synthesis
 Inhibits RNA synthesis
 Metabolite (FdUMP) binds with thymidylate synthetase  inhibit dUMP conversion to dTMP 
thymineless death
 AE: myelosuppression, mucositis, hand-foot syndrome (more common with capecitabine+)
 IV for adenocarcinoma, especially colorectal cancer
 Metastatic CA of breast and GIT in combination with other agents
 Topical treatment of basal cell CA, premalignant keratosis of the skin
 Severe recalcitrant psoriasis
Cytarabine  MOA and AE similar to 5-FU
 Metabolites (ara-CTP) block DNA synthesis
 Only in hematologic malignancies, NOT solid tumors
 Most important antimetabolite used for Acute Myelocytic Leukemia; single most effective agent for
induction of remission
 Non-Hodgkin’s lymphomas
 Acute Lymphocytic Leukemia
Capecitabine+
Gemcitabine
Floxuridine
ANTIBIOTICS “Baby Duguan, Mommy Panic Agad, I’M DEaD”
“Blue(Bleo) ducks(Dactino) met(Mito) on a picnic(Plica) with ants(Anthra) to talk about Mito(Mitoxanthrone), their friend
who DIED(Doxo, Ida, Epi, Dauno) on the throne”
Bleomycin  MOA: binding to DNA  single and double strand breaks following free radical formation, and inhibition of DNA
biosynthesis
o The fragmentation of DNA due to oxidation of a DNA-bleomycin-FE (II) complex and leads to
chromosomal aberrations
o CCS, cause accumulation of cells in the G2 phase
 Uses: Significant antitumor activity versus squamous cell cancer (of the skin, cervix, and vulva), head and neck
cancers, lungs, lymphomas, testicular tumors, germ cell tumors
 Adverse Effect:
o Pulmonary toxicity is dose-limiting for bleomycin. Present as pneumonitis
o Minimally myelo- and immunosuppressive but can cause unusual cutaneous
Dactinomycin  MOA: binds to double helical DNA, blocking transcription: causes single stranded breaks
 Uses:
o Most important rhambsomyosarcoma and Wilms’ Tumor
o Others: Ewing’s tumor, Kaposi’s sarcoma, chorioCA
 Adverse Effect:
o Local toxic extravasation
o Radiation recall reaction
Plicamycin
Anthracyclines  Rubicins [red] (except for Mitoxanthrone [blue])
 Exert cytotoxic action through:
o Inhibition of topoisomerase II
o High affinity binding to DNA through intercalation blocking DNA and RNA, and DNA strand scission
 o Generation of semiquinone free radicals and oxygen free radicals through iron- dependent, enzyme
mediated process
o Binding to cellular membrane to alter fluidity and ion transport

 Adverse effects:
o Main dose limiting toxicity: myelosuppression with neutropenia
o Mucositis
o Cardiotoxicity
 Dexrazoxane, iron chelating agent, is approved to prevent anthracycline-induced cardiotoxicity
o Radiation recall reaction
Idarubicin+
Mitoxanthrone+  MOA: binds to DNA to produce strand breakage and inhibits both DNA and RNA synthesis
 Adverse Effect: Bluish discoloration of fingernails, sclera and urine
Doxorubicin  MOA: Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks; inhibits TOP II;
intercalates into DNA
 Uses
o Acute leukemia, malignant lymphoma, solid tumors (breast CA)
o Metastatic thyroid CA- probably the BEST available agent
o Hodgkin’s and non-Hodgkin’s lymphoma, ovarian CA, lung CA, Wilm’s tumor, neuroblastoma
 Adverse Effects:
o Cardiomyopathy - dose-related and often IRREVERSIBLE local tissue necrosis
o RED discoloration of urine
o Adriamycin flare- benign local allergic reaction; erythematous streaking near site of infusion
Epirubicin+
Daunorubicin+  MOA: same as Doxorubicin
 Uses: ALL (acute lymphocytics leukemia) and AML (acute myeloid leukemia
 Adverse Effects: Nausea and vomiting, fever, RED urine (not hematuria)
ALKYLATING AGENTS
Nitrogen Mustards “CYCLO Met CHLoe In Mecca”
Cyclophosphamide  Favorable therapeutic index
 Broadest spectrum of activity of all the alkylating agents
 Activated in the liver and converted to cytotoxic phospharamide and acrolein in cells
 Oral, IM or IV
 Renal excretion
 AE: Sterile hemorrhagic cystitis
o Hematuria – accumulation of acrolein in the urinary bladder, irritates the mucosa
o Antidote: MESNa+ (2-mercaptoethane sulfonate sodium) given through IV – detoxifies the
metabolite by donating sulfhydryl to acrolein
 Marked alopecia
 Less severe thrombocytopenia
 Water intoxication
 Single agent for Burkitt’s lymphoma
 Non-Hodgkin’s lymphomas and breast CA in combination with other agents
Melphalan  Slowest acting nitrogen mustard
 Standard agent for patients with chronic lymphocytic leukemia and primary (Waldenström’s)
macroglobulinemia
 AE:
o Myelosuppressive action usually moderate, gradual, and rapidly reversible
o Increased incidence of secondary leukemia and other tumors in patients treated for
polycythemia vera and breast CA

Chlorambucil  Oral use for multiple myeloma

 Toxicity: hematological
Ifosphamide
Mechlorethamine
Nitrosureas “CarLo STRuggles Every SEM”
Carmustine+  Highly lipophilic, can cross the BBB
 MOA: forms DNA cross-links, inhibits DNA synthesis and function
 Use
o Malignant astrocytomas and malignant tumors of the brain
o Hodgkin’s and Non-Hodgkin’s Lymphoma
 Toxicity: N&V (acute), myelosuppression (chronic)
Lomustine  Lipophilic, can cross BBB
 MOA: forms DNA cross-links, inhibits DNA synthesis and function
 Use: Brain cancer
 Toxicity: N&V (acute)
Streptozocin
Estramustine+
Semustine
Non-Classical Alkylating Agents “PuROng DACila si BEN”
Procarbazine+  Orally active methylhydrazine derivative
 Use: Hodgkin’s and non-Hodgkin’s lymphoma and brain tumors
 Adverse Effect: Secondary cancer (acute leukemia) higher risk than other alkylating agents
Bendamustine  Bifunctional alkylating agent consisting of purine benzimidazole ring and nitrogen mustard moiety
 MOA: forms cross links with DNA → inhibition of DNA synthesis and function
 Use: chronic lymphocytic leukemia, multiple myeloma, breast CA, Hodgkin’s and non-Hodgkin’s
lymphoma
 Adverse Effects: Myelosuppression, Nausea, Vomiting
Dacarbazine  Triazene derivative
 Use: malignant melanoma, Hodgkin’s lymphoma, soft tissue sarcomas, and neuroblastoma
 Adverse effects: Myelosuppression, Nausea, Vomiting
 This agent is a potent vesicant, and care must be taken to avoid extravasation during administration
Platinum Analogs “PLATINUM player sa COC”
Cisplatin  Major antitumor activity in broad range of solid tumors
 When used in combination regimens, it has led to the cure of non-seminomatus testicular cancer
 Extensively cleared by the kidney and excreted in the urine. Does modification is required in patients
with renal dysfunction
 Adverse effects: Renal toxicity, Gastrointestinal toxicity
Oxaliplatin  Third generation platinum analog
 Second line therapy in combination with 5-FU and leucovorin, termed FOLFO regimen, for metastatic
colorectal cancer
 Adverse effect (Main dose): limiting toxicity: Neurotoxicity
Carboplatin+  Second generation platinum analog
 Broad range of antitumor activity against solid tumors
 Widely used in transplant regimens to treat refractory hematologic malignancies
 Adverse effect: Main dose-limiting toxicity is myelosuppression, Lesser renal and GI toxicity
NATURAL PRODUCTS
Mitotic Inhibitors
Vinca Alkaloids  From Vinca rosea or periwinkle plant
 MOA: bind to tubulin inhibits assembly of
microtubules arrest at metaphase (M- phase
specific) cells division is halted cell death
 Pharmacokinetics:
o Unpredictable GI absorption, thus given IV
o Metabolized by CYP450
o Excreted in the feces via hepatobiliary system
o Modify dose in case of liver dysfunction
Vincristine o Use: Acute lymphoblastic leukemia in children, also in hematologic malignancies (Hodgkin’s and non-
Hodgkin’s lymphomas), multiple myeloma, and pediatric tumors (rhabdomyosarcoma, neurblastoma, Ewing’s
sarcoma, and Wilm’s tumor)
o Adverse effects: dose limiting toxicity- Neurotoxicity (peripheral sensory neuropathy of hands and fingers-
“stocking glove neuropathy”)
o “VinCristine” for CNS (neurotoxicity)
Vinblastine o Use: Hodgkin’s and non-hodgkin’s lymphoma, breast cancer, and germ cell cancer
o Adverse effect: myelosuppression
o “VinBlastine” for bone marrow (myelosuppression)
Taxanes  From bark of Taxus sp. or Pacific yew tree
 MOA: bind to tubulin promotes microtubule formation (allow assembly) prevent depolymerisation
of microtubules/ disassembly traps cells in M phase (M- phase specific)
 Use: Breast and ovarian CA\
Paclitaxel  MOA: Functions as a mitotic spindle poison via high-affinity binding to microtubules with enhancement of
tubulin polymerization
 PK: metabolized by CYP450, 80% excreted in feces
 Use: Solid tumors (ovarian CA, advanced breast CA),non small cell lung CA (NSCLC), and small cell
lung CA (SCLC), AIDS related Kaposi’s sarcoma
 Adverse effects: neutropenia, anemia, leucopenia, diarrhea, muscle and joint pain, hair loss, nausea,
and vomiting
Docetaxel+  MOA: metabolism, and elimination identical to paclitaxel
 Use: second line therapy for advance breast CA and NSCLC
 Adverse effect: radiation recall dermatitis
Topoisomerase Inhibitors
Epipodophyllotoxins  MOA: inhibit topoisomerase II
 From the root of Podophyllumpeltatum (American mandrake, mayapple)
Etoposide  From the root of Padophyllum peltatum (American mandrake, mayapple)
 Semisynthetic derivative of podophyllotoxin
 Oral BA 50%; 30-50% excreted in urine
 Dose reduction in patients with renal dysfunction
  Use: germ cell cancer, small cell and NSCLC, Hodgkin’s and non- Hodgkin’s lymphomas, and gastric
cancer
Campothecins  From Camptotheca acuminata (Happy Tree or xi shu)
 MOA: inhibit topoisomerase I
o TOP I: makes nicks or breaks in DNA single strand during replication to remove torsion caused by DNA
unwinding and then religates after
o Once nicks have been produced by topoisomerase, the drug binds to DNA- TOP I complex which prevents
re-ligation of the single strand → broken DNA strands will be replicated
 CCS, S-phase specific
Ironotecan+  Prodrug; converted in the liver by carboxylesterase to SN- 38 metabolite (1000x more potent)
 Eliminated in the bile and feces (reduce dose in patients with liver dysfunction
 Use: metastatic colorectal CA
 Adverse Effect: myelosuppression and diarrhea
Topotecan  Renal excretion (reduce dose in patients with renal dysfunction)
 Use: second line therapy for ovarian CA and SCLS
L-asparaginase  From E. coli
 MOA: hydrolyzes/depletes L-asparagine  inhibits protein synthesis in cells that are unable to synthesize
their own asparagines
 Unlike most of our cells, cancer cells in acute lymphocytic leukemia (ALL) cannot synthesize L-
asparagines as they lack asparagines synthetase
 Used to treat childhood ALL (acute lymphoblastic leukemia)
 Adverse Effects: Hypersensitivity, no bone marrow suppression
HORMONES
Glucocorticosteroids  Prednisone
 MOA: interfere with lymphoid proliferation and cause dissolution of lymphocytes lymphocytopenic
 Uses: leukemias and lymphomas
 Side Effects: cushingoid features, Na+ and water retention, osteoporosis, peptic ulcer
Estrogens  Estradiol, Conjugated estrogen
 Uses: prostate cancer, male breast cancer
Progestins  Megestrol acetate
 Uses: endometrial cancer
Androgens  Testosterone, Fluoxymesterone
 Uses: female breast cancer
 Side effects: Females will start to look like males (e.g. hair growth, deepening of the voice)
Tamoxifen  MOA: compete with estradiol for binding to estrogen receptors
 Thus, this results to a decrease in the autocrine stimulation of breast cancer growth (2017A)
 Uses: Drug of choice for palliative treatment of advanced breast cancer
 First line hormonal treatment for breast CA that is ER positive (2017A)
 AE: hot flushes, vaginal dryness, nausea (symptoms similar to menopause)
Flutamide,  Uses: prostate cancer, to eliminate the effect of adrenal androgens after orchiectomy
Cyproterone+
acetate
Leuprolide+,  Use: prostate cancer
Goserelin, Buserelin

EGFR TKIs EGFR MAbs

Erlotinib, Gefitinib Cetuximab
EGFR (Egg) cetuximab (sits) on erlotinib (Earl)
Oral: hepatic CYP3A4 Intravenous Gefitinib (Geoff).
metabolism
Use: non-small cell Use: head & neck
lung cancer, pancreatic squamous cell CA, colon CA
CA (Erlotinib)
Common AE: Common AE:
diarrhea, pustular diarrhea, acneiform rash
rash Rare: interstitial lung
Rare: liver/renal toxicity SJS disease, anaphylaxis

HER2/Neu TKIs HER2/Neu MAbs

Lapatinib Trastuzumab
Oral: hepatic CYP3A4 Intravenous
metabolism
Use: breast CA NOT Use: HER2/Neu-
responsive to Trastuzumab overexpressing metastatic
breast CA
Common AE: diarrhea, Common AE: infusion
pustular rash reactions (fever, chills)
Rare: Heart failure
 VEGF TKIs VEGF MAbs “Vegetable garden in Beverly hills is Sunny and
Sunitinib, Sorafenib, Bevacizumab Peaceful with Zora”
Pazopanib
Oral: hepatic CYP3A4 Intravenous
VEGR (Vegetablegarden) Bevacizumab
metabolism (Beverlyhills) Sunny (Sunitinib) Pazopanib
Use: renal cell cancer, GIST Use: renal cell cancer, (Peaceful) Sorafenib (Zora).
lung cancer, colorectal
cancer
Common AE: Common AE: bleeding,
Hypertension, bleeding, hypertension, decreased
fatigue wound healing
Rare: arterial Rare: arterial TE, GI
thromboembolism perforation