CHEMOTHERAPY

Dr.M.TorfehnezhadPediatrician

Definition:

Chemotherapy• The treatment of cancer using specific

chemical agents or drugs that are destructive to malignant cells and tissues. The term comes from two words that mean "chemical" and "treatment."

Cytotoxic• literally translated means ‘toxic to cells’.

The Cell Cycle

The Cell Cycle

Mitosis

Cell Biology: Mitosis

A cell in mitosis

Normal Cell Characteristics:

Metabolism. Strictly controlled & predictable

Maturation & Specialisation. Occurrs before dividing. Strictly controlled.

Reproduction = Cell deathContact Inhibition. Mechanism for

switching off division when in contact with different cells

Recognition. Like cells stay together.

Cancer Cell Characteristics:

Unchecked & Uncontrolled GrowthLoss of contact inhibitionLoss of capacity to differentiateIncreased growth fractionChromosomal InstabilityCapacity to metastasiseAltered biochemical properties

Chemotherapy and Cancer Cells

Cell Cycle specific :Most active against cells in a specificphase therefore need prolonged exposureor repeated doses.

Cell Cycle Non-specific:Most effective against actively dividingcells

Chemotherapy

Chemotherapy may be used conventionally to:

Cure patientsProlong survivalPalliative care symptom control

Chemotherapy

Combination Therapy. Prevents resistance.Adjuvant Therapy. Administered after primary therapye.g.SurgeryNeo adjuvant Therapy: Given before surgery to reducetumour size.

Chemotherapy

Over 50 different chemotherapy drugsAdministered as an outpatient or inpatientdepending on toxicity

Modes of administration include: Oral e.g. Methotrexate, Hydroxyurea IV: Canula/Indwelling Central Venous Catheter Sub cut Intracavity e.g pelvic cavity, bladder Intrathecal. Can be fatal if wrong drug

administered!

Intrathecal Chemotherapy

Drugs Used in Cancer Chemotherapy

Cytotoxic AgentsAlkylating AgentsAntimetabolitesCytotoxic antibioticsPlant derivatives

HormonesSuppress nat’l hormone secr’n or

antagonize hormone actionMisc (mostly target oncogene products)

Rand 50.3

Alkylating Agents

Contain chemical groups that bind cell nucleophiles

Alkylating Agents

Cisplatin (Platinol), Mechlorethamine (Mustargen) and Cytoxan are commonly used agents in this category

Carboplatin- more myelotoxicAction: substitutes an alkyl chemical

structure for a hydrogen atom in the DNAThis results in a cross-linking of each

strand of DNA, thus preventing cell division

Alkylating Agents, con’t

Effective against lymphomas, leukemias, myelomas, ovarian, testicular, breast, and pancreatic cancers

Cause bone marrow suppression, alteration in mucous membranes, severe N&V, alopecia

Alkylating Agents, con’t

Can also cause ototoxicity and nephrotoxicity. Be sure the patient is well hydrated before receiving these agents

Cyclophosphamide

Most commonProdrug – liver metab by CYP P450

MFO’sEffects lymphocytes

Also immunosuppressantOral or IV usuallySE’s: n/v, bone marrow dpression, Cytoxan can cause hemorrhagic cystitis

(give MESNA to protect the bladder)

Antimetabolites

These drugs have a structure similar to a necessary building block for the formation of DNA.

These drugs are accepted by the cell as the necessary ingredient for cell growth, but because it is an imposter, it interferes with the production of DNA.

Antimetabolites

Kill cells in S phaseThree main groups

Folate antagonistsPyr analogsPur analogs

Folic Acid Analogs

Folic acid essential for synth purines, and thymidylate

Methotrexate

Higher affinity for enz than does FH2 Inhib’n DNA synth

Pyrimidine Analogs

5-Fluorouracil Competitive inhibitor for thymidylate

synthetase active siteDecr’d DNA synthesis

Gemcitabine

Inhib’s ribonucleotide reductase decr’d nucleotide synth

Cytosine arabinoside (cytarabine) Inhibits DNA polymerase

Gemcitabine – araC analogFewer SE’s

Purine Analogs6-Mercaptopurine, 6-Thioguanine

Inhibit enz’s necessary for purine synthFludarabine

Converted to triphosphateMech action sim to ara-C

Pentostatin Inhibits adenosine deaminase

Catalyzes adenosine inosine Interferes w/ purinemetab, cell prolif’n

Antibiotic Antineoplastic Agents

These agents actually bind DNA, thus inhibiting DNA and RNA synthesis and therefore inhibiting cell growth.

Sadly, these drugs have great potential to cause irreversible cardiomyopathies.

Doxorubicin (Adriamycin) is used for acute leukemias, soft tissue/bone cancers, lymphomas, and breast cancer

Antibiotic Agents, con’t

Adriamycin is also a potent vessicant (will cause tissue necrosis if it infiltrates)

Most dangerous side effect is decreased ejection fraction (normal is 70%). Must do baseline CV assessment prior to beginning Adriamycin (EKG, echo, angiography).

Must reduce the dose of chemo at the first sign of heart failure

Antibiotic agents, con’t

Other side effects include stomatitis, alopecia, bone marrow suppression, hepatic impairment.

Antibiotic agents, con’t

Dactinomycin Interferes w/ RNA polymerase movement decr’d transcr’n

BleomycinGlycopeptideChelates Fe, which interacts w/ O2 Gen’n superoxide and/or hydroxyl radicalsRadicals degrade DNA fragmentation, release of free

basesMost effective in G2, also active against cells in G0Little myelosuppression BUT pulmonary fibrosis

Mitotic Inhibitors

These drugs are also called Vinca-Alkaloids

Work by inhibiting mitosis during cell division

Vinblastine (Velban) and Vincristine (Oncovin) are commonly used agents for ALL, lymphomas, rhabdomyosarcoma)

Mitotic Inhibitors, con’t

Neurotoxicity is a specific side effect for this classification of drugs. Peripheral neuropathy, alteration in bowel and bladder tone (including paralytic ileus), headache, tingling of fingers/hands/toes, ataxia.

Constipation is common due to effects on the autonomic nervous system

Vinca Alkaloids

Etoposide, teniposideFrom mandrake root Inhibit mitoch function, nucleoside

transport, topoisomerase IICampothecins: irinotecan, topotecan

Irinotecan requires hydrolysis active form

Bind, inhibit topoisomerase II

Hormonal Agents

Used to treat neoplasms that are sensitive to hormonal growth controls of the body.

They interfere with growth-stimulating receptors on target tissues.

Corticosteroids are considered hormonal agents. They retard lymphocytic proliferation, so they help with lymphocytic leukemias and lymphomas.

Hormonal Agents, con’t

Corticosteroids also decrease edema associated with tumor growth, especially in or around the brain, spinal cord, and mediastinum. Will decrease cerebral edema.

Androgens (testosterone) may be used to treat advanced breast cancer

Hormonal Agents, con’t

Anti-Estrogen drugs (Tamoxifen) block the uptake of estrogen and therefore are good for tumors that contain high concentrations of estrogen receptors

Estrogen may be used to treat androgen-sensitive cancers, such as prostate cancer

Progestins (Depo-Provera and Megace) are used to treat endometrial cancer

Chemotherapy Side Effects

Chemotherapy targets cells which are dividing rapidly.

Chemotherapy cannot distinguish between normal cells and cancer cells

Healthy Cells which have a high rate of growth and multiplication include cells of the bone marrow, hair, GI mucosa and skin.

Side effects greatest in other rapidly-dividing cellsBone marrow toxicity Impaired wound healingHair follicle damage Gi epith damage Growth in childrenGametesFetus

May themselves be carcinogenic

Chemotherapy Side effects contd…

Side effects may be drug specific e.g. anthracyclines and cardiotoxicity, vinca alkaloids and neuropathy/constipation, bleomycin and pulmonary fibrosis

Severity of side effects varies between drugs.

Side effects often occur 7-14 days post treatment.

Side Effects: Acute

Tumour Lysis Syndrome. A Metabolic Emergency.Occurrs due to rapid cell lysis (death) &

large amounts of cell metabolites in blood.

If untreated can lead to acute renal failure, cardiac arrest and death.

Side Effects: Acute

Neutropenic Sepsis:Occurs due to Bone Marrow Failure andpoor immune response to infection. Predisposing factors include:NeutropeniaUnderlying diseaseChemotherapyVenous access devices

Neutropenic Sepsis

Severe overwhelming infection where inadequate blood flow to the tissues results in cellular dysfunction and, if not reversed, eventual organ failure.

Most common micro organism is gram negative

Mortality rate 40-90%

Side Effects: Acute

Haemorrhage• Invading tumours e.g gastric MALT

lymphomas• Haemorrhagic Cystitis related to high

dose Cyclophosphomide

Anaphylactic Reaction

Side Effects:Bone Marrow

Neutropenia:

Increased risk of infection.

Anaemia:

Tiredness, lethargy & breathlessness

Thrombocytopenia:

Increased risk of bleeding

Side Effects: Gastro-Intestinal

Nausea & VomitingDiarrhoea & constipationLoss of appetiteTaste ChangesMucositis

Side Effects

Example of Grade 4 Mucositis

Side Effects: Body Image

Hair LossWeight Loss/ Weight GainLong term central venous cathetersSkin changes (colour, rashes, sensitivity

to sunshine, dry)

Side Effects: Other

Fatigue: Often multi-factorialPeripheral neuropathyAltered Kidney FunctionChanges in hearing (high dose Cisplatin)Cardiac Toxicity (Doxorubicin/

Idarubicin)Late Effects: Infertility, secondary

malignancy, growth retardation.

Key Points:

Chemotherapy is a major treatment in curing or prolonging survival in cancer patients

It has a wide range of side effects depending on the drugs given.

Nurses have a key role to play in caring for a patient receiving chemotherapy

Safety issues are paramount in administration.

Summary:

The potential benefit to the patient of treatment as an option must

always outweigh the toxic effects.

Thank You

NCCN2012 Recommendations by Risk Category

High (>90% emetic risk)High (>90% emetic risk)

Including AC containing regimensIncluding AC containing regimens

Three-drug combination of a HTThree-drug combination of a HT33

serotonin receptor antagonist, serotonin receptor antagonist, (palonosetron preferred-NCCN) (palonosetron preferred-NCCN) dexamethasone, and aprepitantdexamethasone, and aprepitant

Moderate (>30% to 90% emetic Moderate (>30% to 90% emetic risk)risk)

Two-drug combination of a HTTwo-drug combination of a HT33

serotonin receptor antagonist and serotonin receptor antagonist and dexamethasone (+/-aprepitant for dexamethasone (+/-aprepitant for selected patients)selected patients)

Low (10% to 30% emetic risk)Low (10% to 30% emetic risk) Dexamethasone 8-12 mgDexamethasone 8-12 mg

Minimal (<10% emetic riskMinimal (<10% emetic risk No antiemetic routinelyNo antiemetic routinely

Thank YouThank You

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