Pharm-D Pharmacotherapeutics 3rd Year notes [ONCOLOGY]

1. PHARMACOTHERAPEUTICS –II: CHAPTER – IV ONCOLOGY
BASIC PRINCIPLES OF CANCER THERAPY
INTRODUCTION:-
PRINCIPLES OF CANCER THERAPY:-
 The ultimate aim of cancer therapy is to totally eradicate the cancer.
When eradication is not possiblethe next goal of cancer therapy is
palliation.
 The palliative therapy aims to achieve amelioration of
symptoms,preservethequality of life and to prolong longevity.
 The choice of therapy depends upon the location and grade of the tumor
and the stage of the disease, as well as the general state of the patient
(performancestatus).
 A number of experimental cancer treatments are also under
development.
 Under currentestimates, two in five people will havecancer at some
point in their lifetime.
 Complete removalof the cancer without damage to the rest of the body
(that is, achieving cure with near-zero adverseeffects) is the ideal goal of
treatment and is often the goal in practice.
 Sometimes this can be accomplished by surgery, butthe propensity of
cancers to invade adjacent tissueor to spread to distant sites by
microscopic metastasis often limits its effectiveness; and chemotherapy
and radiotherapy can have a negative effect on normalcells.[2]
 Therefore, cure with nonnegligible adverseeffects may be accepted as a
practical goal in some cases; and besides curative intent, practical goals
of therapy can also include :-
1. suppressing thecancer to a subclinical state and maintaining that
state for years of good quality of life (that is, treating the cancer as
a chronic disease),
2.palliative care without curative intent (for advanced-stagemetastatic
cancers).
 Because "cancer" refers to a class of diseases, it is unlikely that there will
ever be a single "curefor cancer" any more than there will be a single
treatment for all infectious diseases.
 Angiogenesis inhibitors were once thought to have potential as a "silver
bullet" treatment applicable to many types of cancer, but this has not
been the case in practice.

2. TYPES OF TREATMENTS:-
 The treatment of cancer has undergone evolutionary changes as
understanding of the underlying biological processes has increased.
 Tumor removalsurgeries havebeen documented in ancient Egypt,
hormonetherapy and radiation therapy weredeveloped in the late 19th
Century.
 Chemotherapy, immunotherapy and newer targeted therapies are
products of the 20th century
 As new information about the biology of cancer emerges, treatments
will be developed and modified to increase effectiveness, precision,
survivability, and quality of life.
There are 4 modalities of cancer therapy:
1. Surgery
2. Radiation including photodynamic therapy
3. Chemotherapy including hormonaltreatment
4. Biologic therapy including immunotherapy.
SURGERY:-
 In theory, non-hematological cancers can be cured if entirely removed
by surgery, butthis is not always possible.
 When the cancer has metastasized to other sites in the body prior to
surgery, completesurgicalexcision is usually impossible.
 In the Halstedian model of cancer progression, tumors grow locally,
then spread to the lymph nodes, then to the rest of the body.
 This has given riseto the popularity of local-only treatments such as
surgery for smallcancers.
 Even small localized tumors are increasingly recognized as possessing
metastatic potential.
 Examples of surgicalprocedures for cancer include mastectomy for
breastcancer, prostatectomy for prostatecancer, and lung cancer
surgery for non-smallcell lung cancer
 . The goal of the surgery can be either the removal of only the tumor, or
the entire organ.
 A single cancer cell is invisible to the naked eye but can regrow into a
new tumor, a process called recurrence.
 For this reason, the pathologist will examine the surgicalspecimen to
determine if a margin of healthy tissue is present, thus decreasing the
chance that microscopic cancer cells are left in the patient.

3.  In addition to removal of the primary tumor, surgery is often necessary
for staging, e.g. determining the extent of the diseaseand whether it
has metastasized to regional lymph nodes.
 Staging is a major determinant of prognosis and of the need for adjuvant
therapy. Occasionally, surgery is necessary to controlsymptoms, such
as spinal cord compression or bowel obstruction.
 This is referred to as palliative treatment.
 Surgery may be performed before or after other forms of treatment.
Treatment beforesurgery is often described as neoadjuvant.
 In breastcancer, the survivalrateof patients who receive neoadjuvant
chemotherapy are no different to those who are treated following
surgery.]
 Giving chemotherapy earlier allows oncologists to evaluate the
effectiveness of the therapy, and may make removalof the tumor
easier.
 However, the survivaladvantages of neoadjuvanttreatment in lung
cancer are less clear.
 Surgicalmodality is useful in prevention, diagnosis,staging, and
eradication of cancer.
 Itis also usefulin palliation and rehabilitation.
RADIATION THERAPY:-
 Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation)
is the use of ionizing radiation to kill cancer cells and shrink tumors.
 Radiation therapy can be administered externally via external beam
radiotherapy (EBRT) or internally via brachytherapy.
 The effects of radiation therapy are localised and confined to the region
being treated.
 Radiation therapy injures or destroys cells in the area being treated (the
"target tissue") by damaging their genetic material, making it impossible
for these cells to continue to grow and divide.
 Although radiation damages both cancer cells and normal cells, most
normal cells can recover from the effects of radiation and function
properly.
 The goal of radiation therapy is to damage as many cancer cells as
possible, while limiting harm to nearby healthy tissue.
 Hence, it is given in many fractions, allowing healthy tissue to recover
between fractions.
 Radiation therapy may be used to treat almost every type of solid tumor,
including cancers of the brain, breast, cervix, larynx, liver, lung,
pancreas, prostate, skin, stomach, uterus, or softtissuesarcomas.

4.  Radiation is also used to treat leukemia and lymphoma. Radiation dose
to each site depends on a number of factors, including the radio
sensitivity of each cancer type and whether there are tissues and organs
nearby that may be damaged by radiation.
 Thus, as with every formof treatment, radiation therapy is not without
its side effects.
 Radiation therapy kills cancer cells by damaging their DNA (the
molecules inside cells that carry genetic information and pass it from
one generation to the next) (1).
 Radiation therapy can either damage DNA directly or create charged
particles (freeradicals) within the cells that can in turn damagethe DNA.
(2)
 Radiation therapy can lead to dry mouth from exposureof salivary
glands to radiation.
 The salivary glands lubricate the mouth with moistureor spit. Post
therapy, the salivary glands will resumefunctioning but rarely in the
same fashion.
 Dry mouth caused by radiation can be a lifelong problem.[10]
 The specifics of your brain cancer radiation therapy plan will be based
on severalfactors, including the type and sizeof the brain tumor and the
extent of disease.
 External beam radiation is commonly used for brain cancer. The area
radiated typically includes the tumor and an area surrounding the
tumor.
 For metastatic brain tumors, radiation is sometimes given to the entire
brain.
 Radiation therapy uses special equipment to send high doses of
radiation to the cancer cells.
 Most cells in the body grow and divide to form new cells.
 But cancer cells grow and divide faster than many of the normal cells
around them.
 Radiation works by making smallbreaks in the DNA inside cell.
 Radiation might not be a choice of treatment if the tumour was
diagnosed on the late stageor is located on vulnerable places.
 Moreover, radiation causes significantside effects if used in children
aged 0–14.
 Itwas determined to be a beneficial treatment but it causes significant
side effects that influence the lifestyle of the young patients.

5.  Radiotherapy is the useof high-energy rays, usually x-rays and similar
rays (such as electrons) to treat disease. Itworks by destroying cancer
cells in the area that's treated.
 Although normalcells can also be damaged by radiotherapy, they can
usually repair themselves, but cancer cells can't.
 If the tumour was found on the late stage, it requires patients to have
higher radiation exposurewhich might be harmfulfor the organs.
 Radiotherapy is determined to be an effective treatment in adults but it
causes significantside effects that can influence patients` daily living.
 In children radiotherapy mostly causes long-term side effects such as
hearing loss and blindness.
 Children who had received cranial radiotherapy are deemed at a high
risk for academic failure and cognitive delay.
 Study by Reddy A.T. determined the significant decreasein IQ with
higher doses of radiation, specifically for children with brain tumours
 . Radiation therapy is not the best treatment for brain tumours,
especially in young children as it causes significantdamages.
 There are alternative treatments available for young patients such as
surgicalresection to decrease the occurrenceof side effects.
 Tumour tissue is more sensitiveto radiation than normal tissue
 Hypoxic cells are relatively resistantto radiotherapy
 Non-dividing cells are moreresistant than dividing cells
 A Rad (radiation absorbed dose) is 100 ergs of energy per gm of tissue
 Gy(Gray)—A Gy is 100 rads.
There are three ways of delivering radiation
1. Teletherapy—radiation beams generated at a distance
2. Brachytherapy—encapsulated sources of radiation directly implanted into
tumour tissue
3. Radionuclide therapy
TELETHERAPY
• Teletherapy is mostcommonly used
• All radiation therapy is given for 5 days a week.
CURATIVE RADIATION THERAPY
• Breastcancer
• Hodgkin’s disease
• Head and neck cancer
• Gynaecologicalcancers
• Prostatecancers.
PALLIATIVERADIATION THERAPY

6. • Controlof brain metastasis
• Relief of bonepain frommetastasis
BRACHYTHERAPY
• Brain tumour
• Cervicalcancer.
RADIONUCLIDETHERAPY
• Iodine131 for thyroid cancer
• Strontium 89 and Samarium 153 for bone lesions.
RADIOIMMUNOTHERAPY
Delivering monoclonalantibodies attached to radioisotopes
For example, iodine 131 labelled anti CD 20
Yttrium 90 labelled anti CD 20
Both are active in B cell lymphoma.
PHOTODYNAMIC THERAPY
 Cancer cells selectively absorb certain chemicals like porphyrins and
phthalocyanines.
 When laser light is delivered these cells generate free radicals and the
cells
die.
 This modality is used in skin, lung, ovarian,oesophagealand colorectal
cancers.
TOXICITY OF RADIATION THERAPY
This depends on the field of radiation.
General
Fatigue, anorexia, nausea, vomiting
Local
Mucositis,Skin erythema,Bonemarrow toxicity,Thyroid failure,Cataracts,
Retinal damage,Cessation of salivary secretion,Tasteand smell affection,
Testicular and ovarian affection,Developmentof second solid tumours in the
second decade.
CHEMOTHERAPY:-
 Chemotherapy is the treatment of cancer with drugs ("anticancer
drugs") thatcan destroy cancer cells. In currentusage, the term
"chemotherapy" usually refers to cytotoxic drugs which affect rapidly
dividing cells in general, in contrast with targeted therapy .
 Chemotherapy drugs interfere with cell division in various possible
ways, e.g. with the duplication of DNA or the separation of newly
formed chromosomes.
 Most forms of chemotherapy target all rapidly dividing cells and are not
specific to cancer cells, although some degree of specificity may come

7. fromthe inability of many cancer cells to repair DNA damage, while
normal cells generally can.
 Hence, chemotherapy has the potential to harm healthy tissue,
especially those tissues that have a high replacement rate (e.g. intestinal
lining). These cells usually repair themselves after chemotherapy.
 Because some drugs work better together than alone, two or more
drugs areoften given at the same time. This is called "combination
chemotherapy"; mostchemotherapy regimens are given in a
combination.[11]
 The treatment of some leukaemias and lymphomas requires the use of
high-dosechemotherapy, and total body irradiation (TBI). This treatment
ablates the bone marrow, and hence the body's ability to recover and
repopulate the blood.
 For this reason, bone marrow, or peripheralblood stem cell harvesting is
carried out beforethe ablative part of the therapy, to enable "rescue"
after the treatment has been given.
 This is known as autologous stem cell transplantation.
Classification of Anticancer Drugs
There are six main groups of drugs.
1. Antimetabolites: By inhibiting the folate metabolism,
they interfere with synthesis of purines and
pyramidines.
2. Alkylating agents: Addition of alkylgroup to
constituents of DNA interferes with replication and
transcription of mRNA, leading to cell death.
3. Plant alkaloids: They inhibit cell division by binding
to tubulin and disrupting the mitotic spindle.
4. Antibiotics: They act by intercalating between base pairs and DNA.
5. Taxanes: They act by stabilizing the mitotic spindle
6. Miscellaneous synthetic compounds
Dacarbazine,Cisplatin, Procarbazine, Hexamethylmelamine,
Hydroxyurea
,Mitozantrone.
TARGETED THERAPIES:-
 Targeted therapy, which firstbecame available in the late 1990s, has had
a significant impact in the treatment of sometypes of cancer, and is
currently a very active research area.
 This constitutes the useof agents specific for the deregulated proteins of
cancer cells.

8.  Small molecule targeted therapy drugs aregenerally inhibitors
of enzymatic domains on mutated, overexpressed, or otherwisecritical
proteins within the cancer cell.
 Prominent examples are the tyrosinekinase
inhibitors imatinib (Gleevec/Glivec) and gefitinib (Iressa).
 Monoclonal antibody therapy is another strategy in which the
therapeutic agent is an antibody which specifically binds to a protein on
the surfaceof the cancer cells.
 Examples include the anti-HER2/neu antibody trastuzumab (Herceptin)
used in breastcancer, and the anti-CD20 antibody rituximab, used in a
variety of B-cell malignancies.
 Targeted therapy can also involve small peptides as "homing devices"
which can bind to cell surfacereceptors or affected extracellular
matrix surrounding thetumor.
 Radionuclides which are attached to these peptides (e.g. RGDs)
eventually kill the cancer cell if the nuclide decays in the vicinity of the
cell. Especially oligo- or multimers of these binding motifs are of great
interest, since this can lead to enhanced tumor specificity and avidity.
 Photodynamic therapy (PDT) is a ternary treatment for cancer involving
a photosensitizer, tissueoxygen, and light (often using lasers
 PDTcan be used as treatment for basalcell carcinoma (BCC) or lung
cancer; PDTcan also be usefulin removing traces of malignant tissue
after surgicalremovalof large tumors.
 High-energy therapeutic ultrasound could increasehigher-density anti-
cancer drug load and nanomedicines to target tumor sites by 20x fold
higher than traditional target cancer therapy.
CANCER IMMUNOTHERAPY:-
 Cancer immunotherapy refers to a diverseset of therapeutic strategies
designed to induce the patient's own immune system to fight the tumor.
 Contemporary methods for generating an immune responseagainst
tumours include intravesical BCG immunotherapy for superficialbladder
cancer, and use of interferons and other cytokines to induce an immune
responsein renal cell carcinoma and melanomapatients.
 Cancer vaccines to generate specific immune responses arethe subject
of intensive research for a number of tumours, notably malignant
melanoma and renal cell carcinoma.
 Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate
cancer in which dendritic cells from the patient are loaded with prostatic

9. acid phosphatasepeptides to induce a specific immune responseagainst
prostate-derived cells.
 Allogeneic hematopoietic stem cell transplantation ("bonemarrow
transplantation" froma genetically non-identical donor) can be
considered a formof immunotherapy, since the donor's immune cells
will often attack the tumor in a phenomenon known as graft-versus-
tumor effect.
 For this reason, allogeneic HSCTleads to a higher cure rate than
autologous transplantation for severalcancer types, although the side
effects are also more severe.
 The cell based immunotherapy in which the patients own Natural Killer
cells(NK) and Cytotoxic T-Lymphocytes(CTL) areused has been in
practice in Japan since 1990.
 NK cells and CTLs primarily kill the cancer cells when they are developed.
 This treatment is given together with the other modes of treatment such
as Surgery, radiotherapy or Chemotherapy and called as Autologous
ImmuneEnhancement Therapy (AIET)
 ImmuneCheckpointtherapy focuses on two "checkpoint" proteins,
cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed
death 1 (PD-1).
 Under normalconditions, the immune system utilizes checkpoint
proteins as negative feedback mechanisms to return to homeostasis
once pathogens have been cleared from the body.
HORMONAL THERAPY:-
 The growth of some cancers can be inhibited by providing or blocking
certain hormones.
 Common examples of hormone-sensitivetumors includecertain types
of breastand prostatecancers.
 Blocking estrogen or testosteroneis often an important additional
treatment.
 In certain cancers, administration of hormoneagonists, such
as progestogens may be therapeutically beneficial.
ANGIOGENESIS INHIBITORS
 Angiogenesis inhibitors prevent the extensive growth of blood vessels
(angiogenesis) that tumors requireto survive.
 Some, such as bevacizumab, havebeen approved and are in clinical use.

10.  One of the main problems with anti-angiogenesis drugs is that many
factors stimulate blood vesselgrowth in cells normalor cancerous. Anti-
angiogenesis drugs only target one factor, so the other factors continue
to stimulate blood vesselgrowth.
 Other problems include route of administration, maintenance of stability
and activity and targeting at the tumor vasculature.
SYNTHETIC LETHALITY:-
 Synthetic lethality arises when a combination of deficiencies in the
expression of two or more genes leads to cell death, whereas a
deficiency in only one of these genes does not.
 The deficiencies can arisethrough mutations, epigenetic alterations or
inhibitors of one or both of the genes.
 Cancer cells are frequently deficient in a DNA repair gene. (Also see DNA
repair deficiency in cancer.)
 This DNA repair defect either may be due to mutation or, often,
epigenetic silencing (see epigenetic silencing of DNA repair).
 If this DNA repair defect is in one of seven DNA repair pathways
(see DNA repair pathways), and a compensating DNA repair pathway is
inhibited, then the tumor cells may be killed by synthetic lethality.
 Non-tumorous cells, with the initial pathway intact, can survive.
GENERAL INTRODUCTION TO CANCER CHEMOTHERAPEUTIC AGENTS
INTRODUCTION:-
 Chemotherapy is the treatment of cancer with drugs ("anticancer
drugs") thatcan destroy cancer cells. In currentusage, the term
"chemotherapy" usually refers to cytotoxic drugs which affect rapidly
dividing cells in general, in contrast with targeted therapy .
PRINCIPLES OF CHEMOTHERAPY:-
 Strictly adhere to a treatment plan since the chemo- therapeutic agent
have low therapeuticindex.
 Chemotherapy is usually based on body surfacearea.
 Do a CBC before each cycle of chemotherapy.
 Adjustthe drug dosage for the following condi- tions—weightloss,
neutropaenia, thrombocytopaenia, stomatitis, diarrhoea, limited
metabolic capacity of the drug, liver or renal failure.
 Oraldrug administration—antiemetics if the drug induces nausea and
vomiting.

11.  IV infusion—Proper placementof large calibre needle through a upper
limb vein—veins of antecubi- tal fossa, wrist, or dorsum of the hand
(avoid the armipsilateral to an axillary lymph node resection)
 Indwelling venous catheter in case of poor peripheral venous access.
 Intrathecalchemotherapy is administered for meningeal carcinomatosis
or as CNS prophylaxis. Drain 5-10 mL of CSF and give 10 mg of diluted
methotrexate over 5-10 minutes.
 To decrease the risk of arachnoiditis, patient should remain in the supine
position for 15 minutes after infusion. Slow release cytarabine 50 mg or
ara-C 50-100 mg diluted in 10 mL are alternative drugs.
 Intracavitary instillation—thiotepa 30-60 mg is instilled in the bladder in
CA bladder. Doxorubicin and cisplatin have been used in peritoneal
metastasis.
 Intra-arterialchemotherapy – for achieving high drug concentration at
the tumour site (theoretical advantage).
Ithas severalphases.
 Induction:- Itis the chemotherapy used to achieve a complete
remission.
 Consolidation:- Here chemotherapy is administered to patients who
initially responded to treatment. Maintenance This refers to low dose
outpatient treatment to prolong remission.
 Adjuvantchemotherapy:- This is given after surgicalor radiological
management of primary malignancy.
 Neo-adjuvantchemotherapy:- Itis given in the presence of local disease,
before planned local therapy.
 SurvivalData Median survival: Itquantifies the period of time during
which 50% of studied subjects are alive and 50% are dead.
 Five year survival: Itquantifies the percentage of patients studied who
are alive at five years.
CLASSIFICATION OF ANTICANCERDRUGS:-
1. ALKYLATING AGENTS :-
 Cell-cycle phase-nonspecific agents that substitutean alkyl
group for a hydrogen atom; results in cross-linking of DNA
strands, and interference with replication of DNA and
transcription of RNA.
 Addition of alkyl group to constituents of DNA interferes
with replication and transcription of mRNA, leading to cell
death
 EXAMPLES:-

12. Busulfan , Carboplatin , Carmustine,Chlorambucil
,Cisplatin , Cyclophosphamide, Dacarbazine,Thiotepa
2. ANTITUMOUR ANTIBIOTICS:-
 Inhibitcell division by binding to DNA; interfere with RNA
transcription.
 They act by intercalating between basepairs and DNA.
 EXAMPLES:-
Anthracyclines , Daunorubicin ,Doxorubicin , Epirubicin ,
ldarubicin , Mitoxantrone , Bleomycin , Dactinomycin ,
Mitomycin-C , Plicamycin
3. ANTIMETABOLITES:-
 Interferewith nucleic acid synthesis by substituting drug for
purines or pyrimidines necessary for normalcellular
function.
 By inhibiting the folate metabolism, they interfere with
synthesis of purines and pyramidines.
 EXAMPLES:-
Folic acid analogues:-
methotrexate ,
Nucleoside analogues:-
gemcitabine
Purine analogues :-
capecitabine cladribine fludarabine 6-mercaptopurine
pentostatin, thioguanine
Pyrimidine analogues :-
azacytidine, cytarabine,5-fluorouracil ,
Substituted urea :-hydroxyurea
4. BIOLOGIC RESPONSEMODIFIERS:-
 Modify host's responseto tumours.
 EXAMPLES:-
Cytokines :-Interferon, Interleukin,
Retinoid :-Tretinoin
Monoclonal antibody:- Alemtuzumab ,Rituximab
Tyrosinekinaseinhibitors :- lmatinib mesylate , Dasatinib
, Erlotinib , Gefitinib
5. HORMONES/HORMONEMODIFIERS:-
 Alter cellular metabolism by changing body hormonal
milieu for unfavourabletumour growth.

13.  EXAMPLES:-
Adrenocorticoids :- Glucocorticoids
Androgens:- Fluoxymesterone
Antiandrogens :- Flutamide ,Nilutamide
Antioestrogens :-Tamoxifen
Aromataseinhibitor :- Anastrozole Letrozole •
Oestrogens:- Diethylstilbestrol
Progestins :- Megestrol acetate , Medroxyprogesterone,
Luteinizing hormone-releasing hormoneanalogues :-
Goserelin , Leuprolide
6. NATURAL PRODUCTS:-
 Inhibitmitotic spindle formation and block mitosis.
 EXAMPLES:-
Vinca alkaloids :- Vinblastine, Vincristine, Vinorelbine
Taxanes:- Docetaxel, Paclitaxel
TopoisomeraseII inhibitors: Etoposide, Teniposide
TopoisomeraseI inhibitors:- lrinotecan ,Topotecan
7. MISCELLANEOUS AGENTS:-
 Act by a variety of mechanisms.
 EXAMPLES:-
Bisphosphonates :- Pamidronate,Zoledronic acid
Enzymes :- L-asparaginase,Procarbazine
Others :- Arsenic trioxide ,Thalidomide , Lenalidomide.
BREAST CANCER CHEMOTHERAPY
INTRODUCTION:-
 Breast cancer chemotherapy refers to the use
of cytotoxic drugs (chemotherapy) in the treatment of breastcancer
 Chemotherapy (chemo) uses anti-cancer drugs that may be given
intravenously (injected into your vein) or by mouth.
 The drugs travel through the bloodstream to reach cancer cells in most
parts of the body.
 Occasionally, chemo may be given directly into the spinal fluid which
surrounds thebrain and spinal cord.
TYPES;-
There are three major types of chemotherapy.
1. Neoadjuvantchemotherapy:-

14.  Neoadjuvantchemo is given beforesurgery to slow the growth of
a fast growing cancer or to shrink the sizeof a larger breast
cancer.
 So, neoadjuvantchemo is frequently used to treat locally
advanced cancers, cancers that at the time of diagnosis aretoo big
to be removed by surgery, which can then be removed with less
extensive surgery.
2. Adjuvantchemotherapy:-
 Adjuvantchemo is given after surgery to reduce the risk of
recurrence.
 So, it is used to try to kill any cancer cells that might still exist and
cannot be detected through imaging tests.
3. Palliative chemotherapy:-
 Palliative chemo is used to control (but not cure) the cancer in
settings in which the cancer has spread beyond the breast and
localized lymph nodes.
4. Combined therapies:-
 Combining, for example, non-drug treatments with localized
chemotherapy to limit toxicity and achieve better results.
DRUG REGIMEN:-
 In mostcases (especially as adjuvantor neoadjuvanttreatment),
chemo is mosteffective when combinations of drugs are used.
THE MOST COMMON DRUGS USED FOR ADJUVANTAND NEOADJUVANT
CHEMO INCLUDE:
 Anthracyclines, such as doxorubicin (Adriamycin) and epirubicin
(Ellence)
 Taxanes, such as paclitaxel (Taxol) and docetaxel (Taxotere)
 5-fluorouracil(5-FU)
 Cyclophosphamide(Cytoxan)
 Carboplatin (Paraplatin)
 Most often, combinations of 2 or 3 of these drugs are used.
CHEMOTHERAPY FOR ADVANCED BREASTCANCER:-
 Chemo drugs useful in treating women with breastcancer that has
spread include:
 Taxanes, such as paclitaxel (Taxol), docetaxel (Taxotere), and
albumin-bound paclitaxel (Abraxane)
 Anthracyclines (Doxorubicin, pegylated liposomal doxorubicin,
and Epirubicin)
 Platinum agents (cisplatin, carboplatin)
 Vinorelbine (Navelbine)

15.  Capecitabine (Xeloda)
 Gemcitabine (Gemzar)
 Ixabepilone(Ixempra) Albumin-bound paclitaxel (nab-paclitaxel or
Abraxane)
 Eribulin (Halaven)
 Although drug combinations are often used to treat early breast
cancer, advanced breast cancer more often is treated with single
chemo drugs.
 Still, somecombinations, such as paclitaxel plus carboplatin, are
commonly used to treat advanced breastcancer.
ADMINISTRATION:-
For breast cancer chemotherapy drugs are mostcommonly given:
 into a vein (intravenously)
 by mouth as tablets or capsules (orally)
Intravenous chemotherapy:-
There are various ways thatintravenous chemotherapy can be given
depending on factors such as how easy it is for chemotherapy staff to find
suitable veins and your preferences.
Cannula:-
 The most common way of giving chemotherapy involves inserting a
small needle and plastic tube called a cannula into a vein, either in the
back of the hand or lower arm.
 The needle is removed and the plastic tube left in place.
 The diluted drugs are slowly injected into the vein.
 If a large volume of fluid is used it can be given as an infusion (drip)
through the cannula over a fixed period of time.
 The cannula is taken out after you have had the drugs and a new one is
inserted beforeeach cycle of chemotherapy.
 Chemotherapy is usually given into a vein in the arm on the opposite
side to where you had your surgery, as this may help reducethe risk of
lymphoedema developing (swelling of the arm, hand or breastarea
caused by a build-up of lymph fluid).
 But if this isn’tpossiblethe arm on the same side as your surgery may
be used. This is also the case if you have had surgery on both sides.
 If you have lymphoedema the cannula will be placed in the arm on the
opposite side to whereyou had surgery.
OTHER INTRAVENOUS DEVICES:-
Skin-tunnelledcatheter (Hickmanor Groshong line)
A skin-tunnelled catheter is a fine silicone tube that’s inserted into a vein
through a small cut in the chest.

16. Peripherally insertedcentral catheter(PICC)
A PICC is inserted into a vein in your arm, at or above the bend in your elbow,
and extends into the large vein leading to your heart
Implantedport:-
 An implanted port is a small device connected to a thin tube (catheter).
It’s putunder the skin, usually in the chest or arm. The other end of the
tube goes into a large vein justabove the heart. The port is hidden but
can be felt under the skin.An implanted port is usually put in using a
local anaesthetic.
 Chemotherapy drugs are given directly into the port by puncturing it
each time with a special needle. Itcan also be used to take blood
samples.
 When it needs to be removed a small cut is made over the site of the
port using local aneasthetic. The portis then removed and the catheter
is taken out of the vein. The wound is stitched and covered with a
dressing.
Oral chemotherapy:-
Oralchemotherapy is taken by mouth, either as tablets or capsules, usually at
home.
Electrochemotherapy:-
 Electrochemotherapy, sometimes called ECT, is a treatment for breast
cancer that has spread to the skin.
 Electrochemotherapy is a relatively new treatment and is not available
everywhere.
SIDE EFFECTS:-
Common short-termside effects include:
 Hair loss
 Fatigue
 Loss of appetite
 Nausea and vomiting
 Constipation or diarrhea
 Mouth sores
 Skin and nail changes
 Increased risk of developing infection (dueto fewer white blood cells
that help fight infection)
 Nerve damage (neuropathy)
 Problems with cognitive function that affect memory and concentration
Long-termside effects:-

17.  Certain chemotherapy drugs for breastcancer can causelong-term side
effects, including:
Infertility:-
 One possibleside effect that may not go away is infertility. Some anti-
cancer drugs damageovaries.
 This may cause menopausesymptoms, such as hotflashes and vaginal
dryness.
 Menstrualperiods may become irregular or stop (amenorrhea). If
ovulation ceases, pregnancy becomes impossible.
Osteopeniaandosteoporosis:-
 Women who experience menopauseearly because of chemotherapy
may havea higher risk of the bone-thinning conditions osteopenia and
osteoporosis.
 It's generally recommended that these women have periodic bone
density tests and, possibly, treatments to prevent further bone loss.
Heart damage.:-
 Chemotherapy carries a small risk of weakening the heart muscleand
causing other heart problems.
Leukemia.:-
 Rarely, chemotherapy for breastcancer can trigger a secondary cancer,
such as cancer of the blood cells (leukemia), severalyears after the
chemotherapy was completed.
LEUKEMIA CHEMOTHERAPY
INTRODUCTION:-
 Leukemia, also spelled leukaemia, is a group of cancers that usually
begin in the bone marrow and result in high numbers of abnormal white
blood cells.
 These white blood cells are not fully developed and are
called blasts or leukemia cells.
 Symptoms may include bleeding and bruising problems, feeling tired,
fever, and an increased risk of infections.]
 These symptoms occur due to a lack of normal blood cells.
 Diagnosis is typically made by blood tests or bone marrow biopsy.
TREATMENT:-
 Most forms of leukemia are treated with pharmaceutical medication,
typically combined into a multi-drug chemotherapy regimen.
 Some are also treated with radiation therapy. In somecases, a bone
marrow transplant is effective.

18. ACUTE LYMPHOBLASTIC LEUKEMIA §TREATMENT:-
 Management of ALL is directed towards controlof bone marrow and
systemic (whole-body) disease.
 Additionally, treatment mustprevent leukemic cells from spreading to
other sites, particularly the central nervous system (CNS) e.g. monthly
lumbar punctures.
 In general, ALL treatment is divided into several phases:
1. Inductionchemotherapy:
 Itis used to bring about bone marrow remission. For adults,
standard induction plans include prednisone, vincristine, and
an anthracyclinedrug; other drug plans may include L-
asparaginaseor cyclophosphamide.
 For children with low-risk ALL, standard therapy usually consists
of three drugs (prednisone, L-asparaginase, and vincristine) for the
firstmonth of treatment.
2. Consolidation therapy or intensification therapy :-
 Itis used to eliminate any remaining leukemia cells. There are
many different approaches to consolidation, but it is typically a
high-dose, multi-drug treatment that is undertaken for a few
months.
 Patients with low- to average-risk ALL receivetherapy
with antimetabolite drugs such as methotrexate and 6-
mercaptopurine(6-MP).
 High-risk patients receive higher drug doses of these drugs, plus
additional drugs.
3. CNS prophylaxis (preventivetherapy) :
 Itis used to stop the cancer from spreading to the brain and
nervous systemin high-risk patients. Standard prophylaxis may
include radiation of the head and/or drugs delivered directly into
the spine.
4. Maintenance treatments with chemotherapeutic drugs to prevent
diseaserecurrence once remission has been achieved. Maintenance
therapy usually involves lower drug doses, and may continue for up to
three years.
5. Alternatively, allogeneic bone marrow transplantation may be
appropriatefor high-risk or relapsed patients.[48]
CHRONIC LYMPHOCYTIC LEUKEMIA §TREATMENT:-
Decisiontotreat:-
 Hematologists base CLL treatment on both the stage and
symptoms of the individual patient.

19.  A large group of CLL patients have low-gradedisease, which does
not benefit fromtreatment.
 Individuals with CLL-related complications or more advanced
diseaseoften benefit from treatment.
 In general, the indications for treatment are:
 Falling hemoglobin or platelet count
 Progression to a later stage of disease
 Painful, disease-related overgrowth of lymph nodes or spleen
 An increasein the rate of lymphocyte production[49]
Treatment approach:-
 For most people with CLL, it is incurable by presenttreatments, so
treatment is directed towards suppressing thedisease for many years,
rather than totally and permanently eliminating it.
 The primary chemotherapeutic plan is combination chemotherapy
with chlorambucilor cyclophosphamide, plus a corticosteroid such
as prednisoneor prednisolone.
 The use of a corticosteroid has the additional benefit of suppressing
some related autoimmune diseases, such as immunohemolytic
anemia or immune-mediated thrombocytopenia.
 In resistantcases, single-agent treatments with nucleosidedrugs such
as fludarabine, pentostatin, or cladribine may be successful.
 Younger and healthier patients chooseallogeneic or autologous bone
marrow transplantation in the hope of a permanent cure.
ACUTE MYELOGENOUS LEUKEMIA § TREATMENT:-
 Many different anti-cancer drugs areeffective for the treatment of AML.
Treatments vary somewhataccording to the age of the patient and
according to the specific subtypeof AML.
 Overall, the strategy is to control bone marrow and systemic (whole-
body) disease, while offering specific treatment for the central nervous
system(CNS), if involved.
 In general, mostoncologists rely on combinations of drugs for the
initial, induction phase of chemotherapy. Such combination
chemotherapy usually offers the benefits of early remission and a lower
risk of diseaseresistance.
 Consolidation and maintenance treatments are intended to prevent
diseaserecurrence.
 Consolidation treatment often entails a repetition of induction
chemotherapy or the intensification chemotherapy with additional
drugs.

20.  By contrast, maintenance treatment involves drug doses that are lower
than those administered during the induction phase.
CHRONIC MYELOGENOUS LEUKEMIA § TREATMENT:-
 There are many possibletreatments for CML, but the standard of care
for newly diagnosed patients is imatinib (Gleevec) therapy.
 Compared to mostanti-cancer drugs, it has relatively few side effects
and can be taken orally at home.
 With this drug, more than 90% of patients will be able to keep the
diseasein check for at least five years,so thatCML becomes a chronic,
manageable condition.
 In a more advanced, uncontrolled state, when the patient cannot
tolerate imatinib, or if the patient wishes to attempt a permanent cure,
then an allogeneic bone marrow transplantation may be performed.
 This procedureinvolves high-dosechemotherapy and radiation followed
by infusion of bone marrow from a compatible donor.
 Approximately 30% of patients die from this procedure.
HAIRY CELL LEUKEMIA § TREATMENT:-
 Patients with hairy cell leukemia who are symptom-freetypically do not
receive immediate treatment.
 Treatment is generally considered necessary when the patient shows
signs and symptoms such as low blood cell counts (e.g., infection-
fighting neutrophil count below 1.0 K/µL), frequent infections,
unexplained bruises, anemia, or fatigue that is significant enough to
disruptthe patient's everyday life.
 Typical treatment approach:-
Patients who need treatment usually receive either one week
of cladribine, given daily by intravenous infusion or a simple injection
under the skin, or six months of pentostatin, given every four weeks by
intravenous infusion.
 In mostcases, one round of treatment will producea prolonged
remission.
 Other treatments include rituximab infusion or self-injection
with Interferon-alpha.
 In limited cases, the patient may benefit from splenectomy (removalof
the spleen).
 These treatments are not typically given as the firsttreatment because
their success rates are lower than cladribine or pentostatin.
T-CELL PROLYMPHOCYTIC LEUKEMIA § TREATMENT:-

21.  Most patients with T-cell prolymphocytic leukemia, a rare and aggressive
leukemia with a median survivalof less than one year, require
immediate treatment.
 T-cell prolymphocytic leukemia is difficult to treat, and it does not
respond to mostavailable chemotherapeutic drugs.
 Many different treatments have been attempted, with limited success in
certain patients: purine analogues (pentostatin, fludarabine,
cladribine), chlorambucil, and various forms of combination
chemotherapy (cyclophosphamide, doxorubicin, vincristine,
prednisoneCHOP, cyclophosphamide, vincristine, prednisone[COP],
vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide,
bleomycin VAPEC-B). Alemtuzumab (Campath), a monoclonal
antibody that attacks white blood cells, has been used in treatment with
greater success than previous options.[56]
 Some patients who successfully respond to treatment also undergo stem
cell transplantation to consolidatethe response.
JUVENILE MYELOMONOCYTIC LEUKEMIA §TREATMENT:-
 Treatment for juvenile myelomonocytic leukemia can
include splenectomy, chemotherapy, and bone marrow transplantation.
POSSIBLESIDE EFFECTS:-
 Chemo drugs can affect some normal cells in the body, which can lead
to side effects.
 The side effects of chemo depend on the type and dose of drugs given
and the length of time they are taken.
 Common sideeffects can include:
1. Hair loss
2. Mouth sores
3. Loss of appetite
4. Nausea and vomiting
5. Diarrhea or constipation
 Chemo drugs also affect the normalcells in bone marrow, which can
lower blood cell counts. This can lead to:
1. Increased risk of infections (from having too few normal white blood
cells)
2. Easy bruising or bleeding (from having too few blood platelets)
3. Fatigue and shortness of breath (from having too few red blood cells)
 Most side effects fromchemo go away once treatment is finished. Low
blood cell counts can last weeks, but then should return to normal.

22.  There are often ways to lessen chemo side effects. For example, drugs
can be given to help preventor reduce nausea and vomiting.
1. Low levels of bloodcells:-
 All the drugs used to treat AML make your blood counts fall.
 Low platelet counts:-
 If your platelet counts are low, you may be given drugs or platelet
transfusions to help protect against bleeding.
 Low redblood cell counts:-
 Shortness of breath and extreme fatigue caused by low red blood cell
counts (anemia) may be treated with drugs or with red blood cell
transfusions.
 Low white blood cell counts: Someof the mostserious side effects of
chemo are caused by low white blood cell counts.
 Drugs known as growthfactors, such as filgrastim (Neupogen),
pegfilgrastim(Neulasta), and sargramostim (Leukine), aresometimes
given to increase the white blood cell counts after chemo, to help lower
the chanceof infection.
 However, it’s not clear if they havean effect on treatment success
2. INCREASED RISKOF GETTING AN INFECTION:-
 Signs of an infection include headaches, aching muscles, a cough, a sore
throat, pain passing urine, or feeling cold and shivery..
 Chemotherapy reduces the number of white blood cells in the blood.
This increases your risk of infections. White blood cells help fight
infections.
 When the level is very low it is called neutropenia (pronounced new-
troh-pee-nee-ah).
 You may get antibiotics and drugs thathelp preventfungal and viral
infections beforebefore you have signs of infection or at the earliest
sign that an infection may be developing (such as a fever).
3. LOSS OF FERTILITY:-
Talk to your doctor beforestarting treatment if you think you may wantto
have a baby in the future.
Men:-You may be able to store sperm before starting treatment.Itcan take a
few months or sometimes years for fertility to return to normal. You can have
spermcounts to check your fertility when your treatment is over. Ask your
doctor about it.
Women:-Chemotherapy can cause an early menopause. This stops you from
being able to become pregnant in the future. Talk to your doctor about this

23. before your treatment. It’s sometimes possibleto store eggs or embryos
before treatment.
4. MOUTH SORES AND ULCERS:-
 patient mouth might become soreabout 5 to 10 days after you start
treatment.
 Itusually clears up gradually 3 to 4 weeks after your treatment ends.
 doctor or nursecan give you mouthwashes to help preventinfection.
 You have to use these regularly to get the most protection.
5. HAIR LOSS:-
 patient could lose all your hair. This includes your eyelashes, eyebrows,
underarm, leg and sometimes pubic hair.
 Itusually starts gradually within 2 to 3 weeks after treatment begins.
 patient hair will grow back once your chemotherapy treatment has
finished.
 This can take severalmonths and your hair is likely to be softer.
 Itcan also grow back a different colour or be curlier than before
6. FEELING OR BEING SICK:-
 Feeling or being sick can be severe. Itcan starta few hours after
treatment and last for a few days. Antisickness injections and tablets
can control it.
7. Secondcancers:-
 One of the most serious sideeffects of ALL therapy is an increased risk
of getting acute myeloid leukemia (AML) at a later time.
 This occurs in a small portion of patients after they have received
certain chemo drugs.
 Less often, people cured of leukemia may later develop non-Hodgkin
lymphoma or other cancers. Of course, the risk of getting these second
cancers mustbe balanced againstthe obvious benefit of treating a life-
threatening disease such as leukemia with chemotherapy.
8. Tumor lysis syndrome:-
 This side effect of chemo is mostcommon in patients who have large
numbers of leukemia cells in the body, so it is seen mostoften in the
first(induction) phaseof treatment.
 When chemo kills the leukemia cells, they break open and release their
contents into the bloodstream.
 This can overwhelmthe kidneys, which aren’t able to get rid of all of
these substances at once.
 Excess amounts of certain minerals can also affect the heart and
nervous system. T

24.  his can often be prevented by giving extra fluids during treatment and by
giving certain drugs, such as bicarbonate, allopurinol, and rasburicase,
which help the body get rid of these substances.
Side effects of specific drugs:
Certain drugs mightcause specific side effects. For example:
 Cytarabine (ara-C), especially when used at high doses, can cause
dryness in the eyes and can affect certain parts of the brain, which can
lead to problems with coordination and balance.
 Vincristine can damagenerves, which can lead to numbness, tingling, or
weakness in hands or feet.
 Anthracyclines (such as daunorubicin or doxorubicin) can damage the
heart, so the total dose needs to be watched closely, and these drugs
might not be used in someonewho already has heart problems.
Other organs that could be damaged by certain chemo drugs include the
kidneys, liver, testicles, ovaries, and lungs. Doctors and nurses carefully
monitor treatment to reduce the risk of these side effects as much as possible.
If serious sideeffects occur, the chemo may haveto be reduced or stopped, at
least for a time
CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING
INTRODUCTION:-
 Chemotherapy-inducednauseaandvomiting (CINV) is a common side-
effect of many cancer treatments.
 Nausea and vomiting are two of the most feared cancer treatment-
related side effects for cancer patients and their families.
 In 1983, Coates et al. found that patients
receiving chemotherapy ranked nausea and vomiting as the firstand
second most severeside effects, respectively.
 Up to 20% of patients receiving highly emetogenic agents in this era
postponed, or even refused, potentially curativetreatments.[1]
 Since the 1990s, severalnovelclasses of antiemetics have been
developed and commercialized, becoming a nearly universalstandard in
chemotherapy regimens, and helping to better manage these symptoms
in a large portion of patients.
 Efficient mediation of these unpleasant and sometimes crippling
symptoms results in increased quality of life for the patient, and better
overall health of the patient, and, due to better patient tolerance, more
effective treatment cycles

25. TYPES:-
There are severalsubtypes of CINV. Theclassifications of nausea and vomiting
are:
 Acute: occurring within 24 hours of chemotherapy
 Delayed: occurring between 24 hours and 5 days after treatment
 Breakthrough: occurring despiteprophylactic treatment
 Anticipatory: triggered by taste, odor, memories, visions, or anxiety
related to chemotherapy
 Refractory: occurring during subsequentcycles when antiemetics have
failed in earlier cycles
CAUSE:-
 Emesis is a defense mechanism controlled by the area postrema of
the medulla oblongata.
 There are various sources of input to the vomiting center.
 Receptors on the floor of the fourth ventricle of the brain represent
the chemoreceptor trigger zone.
 The chemoreceptor trigger zone contains dopamine D2
receptors, serotonin 5-HT3 receptors, opioid receptors, acetylcholine
receptors, and receptors for substanceP.
 Stimulation of differentreceptors are involved in different pathways
leading to emesis.
 In the final common pathway, substanceP, which activates
the neurokinin-1 receptor, appears to be involved.[3]
 Additionally, the vagaland enteric nervous system inputs transmit
information regarding the state of the gastrointestinalsystem. Irritation
of the GI mucosa by chemotherapy, radiation, distention, or acute
infectious gastroenteritis activates the 5-HT3 receptors of these inputs.[4]
 Itis now widely known that cytotoxic chemotherapeutic agents causea
detectable increase in blood levels of serotonin (5-HT) and its major
metabolite, 5-Hydroxyindoleacetic acid (5-HIAA).[5]
 The presence of these chemicals in the blood activate 5-HT3 receptors in
the chemoreceptor trigger zone, in turn releasing substanceP, which
activates NK1 receptors to cause an emetic response(vomiting).
PATHOPHYSIOLOGY OF CINV:-
 The pathophysiology of CINV is not entirely understood, however it is
thought to have many contributing pathways.
 Vomiting or emesis occurs when the vomiting center (VC), located in the
medulla near the respiratory center on the floor of the fourth ventricle,
is activated.

26.  Activation of the VC can arise from pathways in the gastrointestinal(GI)
tract, chemoreceptor trigger zone(CTZ), vestibular apparatus, cerebral
cortex or a combination of these pathways (Camp-Sorrell, 2005).
 The VC is sensitive to severalneurotransmitters that are released
through each pathway.
 Activation fromthe vestibular-cerebellar pathway, a result of motion
sickness or when rapid changes in motion occur, is not directly involved
in CINV.
 The two pathways thoughtto be directly involved with CINV are the GI
tract and the CTZ.
 When rapidly dividing enterochromaffin cells located in the GI tract are
damaged, serotonin is released and binds to vagalafferent receptors
that stimulate emesis through the CTZ or directly through the VC.
 The CTZ is a highly vascular organ that is not confined to the blood-brain
barrier and is thereforevulnerable to exposure to chemotherapy from
the blood as well as cerebral spinalfluid (Wickham, 2004).
 The CTZ is located in the area postrema and is near the VC.
 Activation of the VC directly or through the CTZ results in stimulation of
the salivation and respiratory centers as well as control of the
pharyngeal, GI and abdominal muscles.
 The neurotransmitters mostresponsiblefor the activation of the CTZ in
CINV are serotonin and substanceP. Noradrenaline, somatostatin,
enkephalin, acetylcholine, aminobutyric acid, vasopressin and cortisol
can also induced vomiting through the CTZ.
 Though the VC has many neurotransmitter receptors it is mostsensitive
to muscarinic and dopamine.
 Research has primarily focused on the pathophysiology of acute and
delayed CINV, thus the pathophysiology of nausea as a sole entity is less
known.
 Itis thought that nausea is mediated by the autonomic nervous system.
The CTZ is also felt to be more greatly involved in nausea than in
vomiting .
RISK FACTORS:-
 The risk of chemotherapy-induced nausea and vomiting varies based on
the type of treatment received, as well as several outsidefactors.
 Some types of chemotherapy are more proneto causing nausea and
vomiting than others.
 Some chemotheraputic agents may not cause nausea and vomiting on
their own, but may when used in combination with other agents.[6]

27.  Regimens that are linked to a high incidence (90% or higher) of nausea
and vomiting are referred to as "highly emetogenic chemotherapy", and
those causing a moderate incidence (30–90%) of nausea and vomiting
are referred to as "moderately emetogenic chemotherapy".
Some highly emetogenic agents and chemotherapy regimens include:
 Cisplatin
 Dacarbazine
 Cyclophosphamide(>1500 mg/m2
)
 Carmustine(>250 mg/m2
)
 Mechlorethamine
 Streptozocin
Some moderately emetogenic agents and regimens include:
 Carboplatin
 Methotrexate
 Doxorubicin/Adriamycin
 Ifosfamide
 Cyclophosphamide(≤1500 mg/m2
)
Besides the type of treatment, personal factors may put a patient at greater
risk for CINV. Other risk factors include:
 Female sex
 Patient age (under 55 years old)
 History of light alcohol use
 History of previous CINV
 History of nausea and vomiting during pregnancy
 History of motion sickness
 Anxiety or depression
 Anticipation of CINV
TREATMENTS:-
 Antiemetic Therapies
5-HT3 Antagonists
 Dolasetron ,granisetron ,ondansetron ,palonosetron ,tropisetron (not
avail in US)
NK1 Receptor Antagonists
 aprepitant (oral formulation),fosaprepitant(IV formulation)
Corticosteroids
 dexamethasone ,methylprednisone
Miscellaneous Agents
 metoclopramide, compazine,cannabinoids,benzodiazepines
,antihistamines.

28. Several treatment methods are available to help prevent CINV.
Pharmaceutical treatment is generally separated into two types:
prophylactic (preventative) treatment, given before the doseof
chemotherapy agents, and rescuetreatment, given to treat breakthrough
nausea and vomiting.
5-HT3 inhibitors:-
 5-HT3 receptor antagonists are very effective antiemetics and constitute
a great advance in the management of CINV.
 These drugs block one or more of the nerve signals that cause nausea
and vomiting.
 During the first24 hours after chemotherapy, the mosteffective
approach appears to be blocking the 5-HT3 nervesignal[citation needed]
.
 Approved 5-HT3 inhibitors
include dolasetron (Anzemet), granisetron (Kytril, Sancuso),
and ondansetron (Zofran). Their antiemetic effect due to blockadeof
5HT3 receptor on vagal afferent in the gut. in addition they also block 5-
HT3 receptors in CTZ and STN.
 The newest 5-HT3 inhibitor, palonosetron (Aloxi), also prevents delayed
nausea and vomiting, which can occur during the 2–5 days after
treatment.
 Since some patients have trouble swallowing pills, these drugs are often
available by injection, as orally disintegrating tablets, or as transdermal
patches.
NK1 inhibitors:-
 A newer class of drugs known as the NK1 antagonists are a recently
developed class of very efficacious drugs for controlling CINV.
 These drugs areoften used alongside 5HT3 inhibitors and corticosteroids
to form a very potent cocktail of antiemetics that verge on achieving a
nearly complete patient response(that is, completely stopping CINV).[10]
 The substanceP inhibitor aprepitant (Emend), which became available in
2005, is highly effective in controlling nausea and vomiting associated
with cancer chemotherapy.[10]
 Aprepitant has been shown to inhibit both the acute and delayed
emesis induced by cytotoxic chemotherapeutic drugs by blocking
substanceP landing on receptors in the brains neurons.
 This has been proven by Positron Emission Tomography (PET) studies,
which have demonstrated that aprepitant can penetrate the brain and
NK1 receptors in the brain.[11]
 Ithas also been shown to increase the activity of the 5-HT3 receptor
antagonists ondansetron and the corticosteroid dexamethasone, which

29. are also used to prevent nausea and vomiting caused by
chemotherapy.[10]
 Netupitant has recently been approved by USFDA. Ithas also been
marketed in combination with palonosetron. Rolapitant is the newest
addition in the approved NK1 antagonist list.
 Ithas advantage of a very long half life, duration of action is around 150
hours. Rolapitant got its approvalby USFDA in 2015.
OTHER DRUGS:-
 Olanzapine, as well as severalother neuroleptic drugs, havealso has
been investigated for the control of CINV.
 A 2007 study demonstrated Olanzapine's successfulpotential for this
use, achieving a complete response in the acute prevention of nausea
and vomiting in 100% of patients treated with moderately and highly
emetogenic chemotherapy, when used in combination with
palonosetron and dexamethasone.
 Neuroleptic agents are now indicated for rescuetreatment and the
control of breakthrough nausea and vomiting.
 Some studies[14]
and patient groups say that the use
of cannabinoids derived from cannabis during chemotherapy greatly
reduces the associated nausea and vomiting, and enables the patient to
eat.
 Synthesized tetrahydrocannabinol (also oneof the main active
substances in marijuana) is marketed as Marinol and may be practical
for this application.
 Natural medical cannabis is also used and recommended by some
oncologists, though its use is regulated and it is not legal in all
jurisdictions.
 However, Marinolwas less effective than megestrolacetate in helping
cancer patients regain lost appetites.[16]
 A phase III study found no differencein effects of an oral cannabis
extract or THC on appetite and quality of life (QOL) in patients with
cancer-related anorexia-cachexia syndrome(CACS) to placebo.
 Dexamethasone, a corticosteroid, is often used alongside other
antiemetic drugs, as it has synergistic action with many of them,
although its specific antiemetic mechanism of action is not fully
understood.
 Metoclopramide, a dopamine D2 receptor antagonist with possibleother
mechanisms, is an older drug that is sometimes used, either on its own
or in combination with others.

30.  Histamine blockers such as diphenhydramineor meclozine may be used
in rescue treatment
 Lorazepam and diazepam may sometimes be used to relieve anxiety
associated with CINV beforeadministration of chemotherapy, and are
also often used in the case of rescuetreatment.
Alternativetreatments:-
Ginger (Zingiber officinale):-
 There are severalcompounds that have been identified
within ginger that have been shown to possess properties thatare likely
to be beneficial in the treatment of CINV.
 This includes 5-HT3 and substanceP antagonism, modulation of
gastrointestinalmotility, and antioxidant properties.
 There have been multiple clinical trials that haveinvestigated the use of
ginger supplementation as a treatment for CINV.
Other:-
 Non-pharmacologicalapproaches to remedy CINV typically involve small
lifestyle alterations, such as using unscented deodorants and soaps,
avoiding strong scents altogether, and dietary modifications such as
eating severalsmall meals throughoutthe day, eating high-protein, high-
calorie food, drinking lots of clear liquids, and removing spicy, fatty,
fried, or acidic foods fromthe diet.
 Patients may also participate in alternative practices such as self-
hypnosis, relaxation and imagery therapy, distraction, music
therapy, biofeedback, desensitization, or acupressure.