Alkylating drugs.

 treat cancer.
 Develop from the mustard gas agent that were used for chemical warfare before and during
World War 1.

 3 categories
Classic Alkylators
-Chlorambucil.
-Cyclophosphamide.
-Ifosfamide.
-Mechlorethamine.
-melphalan
Nitrosoureas.
-Carmustine.
-Lomustine.
-Streptozocin
Miscellaneous alkylators
-Altretamine.
-Busulfan
-Carboplatin.
-Cisplatin.
-Dacarbazine.
-Oxaliplatin.
-Procarbazine.
-Temozolamide.
-Thiotepa

MOA & DE
 prevents cancer cells from reproducing.
 Alters the chemical structure of cells DNA.
 Characterized by the number of alkylation reactions in which they can participate.
 Bifunctional -two reactive alkyl groups that are able to calculate two sites on the DNA molecule.
 Polyfunctional- several alkylation reactions.

Indication
 solid and hematologic tumors.

Adverse Effects
 GI toxicity and bone marrow suppression.
 Prevented or minimized by prophylactic measures.
 Nephrotoxicity from cisplatin can be prevented by adequately hydrating the patient with IV fluids.
 Extravasation -intravenous catheter punctures the vein or artery and medication leaks
(infiltrates) into the surrounding tissue.
 Doxorubicin, a cytotoxic antibiotic, extravasation can cause severe tissue damage and necrosis
tissue death.
 Interactions
 avoid administering alkylating drugs with other drugs capable of causing similar toxicities.
 Cisplatin -do not administer it with a drug such as aminoglycoside antibiotics (Gentamicin,
Tobramycin, or amikacin) -->results---> additive nephrotoxic effects---> increase likelihood of renal
failure.
 Mechlorethamine and cyclophosphamide---> bone marrow suppression effects & not to be
administered with radiation therapy.

Drug profiles
Cisplatin (platinol)
-contains Platinum.
-Destroys cancer cells by forming cross-links with DNA preventing its replication.
-Treatment of solid tumors such as gallbladder, lung, testicular, and ovarian tumors.
-Available in injectable form only.
-Medication errors resulting in death when this med is confused with carboplatin.
-Best to use both trade name and generic name when dealing with chemotherapy drugs.

Cyclophosphamide (cytoxan)
-Polyfunctional alkylating drug.
-Prodrug requiring in Vivo action.
-Treatment of cancer of the bone , lymph, solid tumors, Leukemia, multiple myeloma, & non-cancer
related illnesses such as prophylaxis for rejection of kidney, heart, liver, bone marrow transplant and
severe rheumatoid disorders.
-Available in oral and injectable forms.

Mechlorethamine (nitrogen mustard, mustargen)

- prototypical alkylating drug.
-Treatment of Hodgkin and non-hodgkin Lymphoma.
-Forming cross-links between two DNA nucleotides which interferes with RNA transcription and
prevents cell division and protein synthesis.
-Parental form only to be administered Intravenouslly or by intracavitary route such as intrapleural or
intraperitoneally.
-Topical for treatment of cutaneous T-cell lymphoma.

Cytotoxic antibiotic antineoplastic drugs

 natural substances produced by the mold streptomyces
 semisynthetic substances and which chemical changes are made in the natural molecule.
 Bone marrow suppression as a common toxicity.
 Bleomycin cause pulmonary toxicity, pulmonary fibrosis and pneumonitis.
 Severe toxicities are heart failure (daunorubicin) and acute left ventricular failure(doxorubicin).
Anthracyclines
daunorubicin
doxorubicin
Epirubicin
idarubicin
valrubicin.

Other cytotoxic antibiotic antineoplastic.

Bleomycin - cell cycle specific drug
Dactinomycin
mitomycin
Mitoxantrone
plicamycin
idarubicin
valrubicin.

MOA
 cell cycle nonspecific drug.
 Intercalation -drug molecule is inserted between the two strands of DNA molecules blocking
DNA synthesis.
 Inhibit the enzyme topoisomerase II which leads to DNA strand breaks.
 Generate free radicals which leads to DNA strand breaks and programmed cell death.

Indications.
-Solid tumors
-hematologic malignancies

Adverse effects
-Hair loss, nausea and vomiting, myelosuppression.
-Toxicity and management of Overdose.
-Large cumulative dose of doxorubicin-->cardiomyopathy. Monitoring of cardiac
function, cumulative dose limitations, and use of dexrazoxane -->decreases the
incidence of this devastating toxicity.
 Interactions.
-Other chemotherapeutic drugs
-With radiation therapy.
-Bleomycin and doxorubicin cause serum digoxin levels to increase =digoxin toxicity.

Drug Profiles

Doxorubicin (Adriamycin)
 Used in many combination chemotherapy regimens.
 Contraindicated in hypersensitivity, severe myelosuppression, risk for severe cardiotoxicity
with large cumulative doses of anthracycline antineoplastic.
 Injectable form.
 Liposomal drug delivery system doxil.
 Drug is encapsulated in a liquid molecule bilayer called lipozone.
 Advantages are reduced systemic toxicity and increased duration of action.
 Extends biologic half-life of doxorubicin to 50-60 hours and increases its affinity for cancer
cells.
 Treatment of ovarian cancer in combination with bortezomib for treatment of multiple
myeloma.

Mitoxantrone (Novantrone)
-Tx of acute nonlymphocytic leukemia & prostate cancers & neurologic disorder multiple
sclerosis
-injectable form

Miscellaneous Antineoplastics
 Bivacizumab
 Everolimus
 Hydroxyurea
 Ipilimumab
 Imatinib
 Mitotane
 Ofatumumab
 Pazopanib
 Romidepsin
 Sorafenib
 Sunitinib
 Hormonal drugs
 Radioactive & related antineoplastic drugs

Drug Profiles
 treat a wide range of neoplasms.
  Hydroxyurea and imatinib administered orally.
 Bevacizumab & mitotane- injectable
 Sipyleucel-T (provenge)- treatment for prostate cancer. Not a chemotherapeutic agent.
Autologous cellular immunotherapy for treatment of asymptomatic or minimally symptomatic
metastatic hormone resistant prostate cancer. Uses the patient's own monocytes that are
activated and then re-infused into the patient. Pre-treated with acetaminophen and
diphenhydramine. Restricted to Physicians who have undergone extensive training.
 Ceritinib (zykadia)- a tyrosine kinase inhibitor indicated for ALK positive lung cancer
unresponsive to other therapies. Breakthrough therapy. Orally on an empty stomach at least
2 hours before and 2 hours after a meal, grapefruit juice should be avoided. Side effects
include bradycardia, severe diarrhea, and nausea and vomiting, requires dose reduction.
Hepatotoxicity, hyperglycemia, QTC prolongation, life-threatening interstitial lung disease or
pneumonitis. Drug interactions conivaptan, strong cyp3a for inhibitors, inducers and drugs
that can prolong the QTC interval.

Bevacizumab
-Angiogenesis inhibitor.
- Angiogenesis is the creation of new blood vessels that supply oxygen and other blood nutrients to
grow in tissues.
- Malignant tumors -angiogenesis occurs within the tumor Mass, promotes continue tumor growth.
 recombinant humanized monoclonal immunoglobulin G1 antibody derived from Mouse
antibodies.
 Compound derived from Mouse tissue is murine.
 Humanization refers to the use of recombinant DNA techniques to make animal-derived
antibody proteins more genetically similar to those of humans.
 Binding to and inhibiting the biological activity of human vascular endothelial growth factor,
VEGF--> Is an endogenous protein that normally promotes angiogenesis in the body.
 Injectable form.
 Contraindications is severe drug allergy two other marine products.
 Treatment of metastatic colon cancer, rectal cancer in combination with 5 fluorouracil, non-
small lung cancer and malignant glioblastoma.
 Adverse reactions-
o cardiovascular system- hypertension or hypotension, DVT.
o CNS- pain, headache, dizziness, asthenia.
o Skin- alopecia, dry skin.
o Metabolism- weight loss, hypokalemia.
o GI- nausea, vomiting, diarrhea, epistaxis, abdominal pain, constipation, GI Hemorrhage.
o Kidneys- nephrotoxicity with proteinuria. Hematopoietic system, leukopenia.
o Respiratory tract- infection.
-Drug interactions include potentiation of the cardiotoxic effect of the anthracycline antibiotic
such as doxorubicin.
Hydroxyurea
 antimetabolite
 interferes with the synthesis of DNA by inhibiting the incorporation of thymidine into DNA.
 Inhibits ribonucleotide reductase which is involved in the conversion of ribonucleotides to
deoxyribonucleotides.
  S & G1 phases of the cell cycle which makes it a cell cycle specific drug.
 Treatment of squamous cell carcinoma with radiation.
 Has Radiosensitized activity.
 Treatment of various types of leukemia.
 Oral form only.
 Adverse reaction include edema, drowsiness, headache, rash, hyperuricemia, nausea,
vomiting, dysuria, myelosuppression, elevated liver enzyme levels, muscular weakness,
peripheral neuropathy, nephrotoxicity, dyspnea, pulmonary fibrosis.
 Interacts with zidovudine, zalcitabine, didanosine (have synergistic effects with Hydroxyurea.)
 Concurrent use with fluorouracil increases risk for neurotoxic symptoms.
 Hydroxyurea can reduce clearance of cytarabine- dosage reduction of cytarabine when used
with hyrdoxyurea.

Imatinib
 Tx of chronic myeloid leukemia
 Inhibiting action of a key enzyme responsible for causing CML.
 Targeted therapy
 Oral form only
 Adverse reactions- fatigue, h/a, rash. Fluid retention, GI & hematologic effects,
musculoskeletal pain, cough, dyspnea.
 Interaction-drugs metabolized by cytochrome P-450 hepatic-amiodarone, verapamil,
warfarin, azole antifungals, antidepressants, antibiotics.
Mitotane
 Adrenal cytotoxic drug
 Tx-inoperable adrenal corticoid carcinoma
 Oral form
 Adverse reactions central nervous system depression, rash, nausea, vomiting, muscle
weakness, headache.
 Interactions include enhanced CNS depressive effects when taken concurrently with other
CNS depressants, benzodiazepines. Increase the clearance of both Warfarin and phenytoin
and reduce their effects. Spironolactone may negate the effects of mitotane.

Octreotide
- management of a cancer related condition called carcinoid crisis in treatment of diarrhea caused
by vasoactive intestinal peptide secreting tumors (VIPomas).

Hormonal antineoplastic.
-Treatment of a variety of neoplasms.
-Sex hormones act to accelerate growth of some common types of malignant tumors like breast and
prostate cancer.
- Administration of hormones with opposing effects or drugs that block the body's sex hormone
receptors.
- Palliative and adjunct therapy.
-Female specific neoplasms such as breast cancer AR aromatase inhibitors anastrozole and
aminoglutethimide. Selective estrogen receptor modulators tamoxifen and toremifen,
progestinsmegestrol, medroxyprogesterone. Androgens- fluoxymesterone, testolactone. Estrogen
receptor antagonist fulvestrant.
-Male specific neoplasms such as prostate cancer anti-androgens bicalutamide, flutamide,
nilutamide. Antineoplastic hormones estramutine