MANAGEMENT OF ADVERSE EFFECTS OF CANCER

CHEMOTHERAPY
1. GENERAL ADVERSE EFFECTS 10.Oral cavity
OF ANTICANCER DRUGS 11.Gonads
2. Immediate ADR: Nausea, 12.Foetus
Vomiting Others:-
3. Myelosuppression/ BONE  Veno occlusive disease of the liver
MARROW SUPPRESSION  Hemorrhagic cystitis
4. Mucositis  Nephrotoxicity
5. Alopecia  Neurotoxicity
6. Teratogenicity  Pulmonary toxicity
7. Anxiety  Cardiotoxicity
8. ANOREXIA  Hand Foot syndrome
9. Hyperuricaemia  Tumour Lysis syndrome


NAUSEA AND VOMITING:-

Nausea and vomiting are common adverse reactions to the antineoplastic drugs.
Emesis; nausea- protective reflexes- to get rid of toxic substances- prevents further
ingestion.
Central emesis center: Chemoreceptor trigger zone in area postrema at bottom of 4 th
ventricle
Solitary Tract nucleus.

 Highly emetogenic- cisplatin, carmustine, cyclophosphamide, dacarbazine,

mechlorethamine, streptozocin
 Moderate emetogenic- doxorubicin, daunorubicin, cytarabine, oxaliplatin,
carboplatin, ifosfamide
 Low emetogenic- Etoposide, 5-FU, gemcitabine, MTX, pemetrexed, mitomycin,
paclitaxel
 Least emetogenic- Vinca alkaloids, cladarabine, bevacizumab.

The primary health care provider may order an antiemetic about 30 minutes before
treatment with the antineoplastic drug begins and continue the antiemetic for several
days after administration of the chemotherapy. The nurse provides small, frequent meals
to coincide with the patient’s tolerance for food.
Greasy or fatty foods and unpleasant sights, smells, and tastes are avoided. Cold foods,
dry foods, and salty foods may be better tolerated.

LOW RISK OF EMESIS:

 PRE- CHEMOTHERAPY
 Dexamethasone
 Metoclopramide± diphenhydramine
 Prochlorperazine ± Lorazepam
 POST- CHEMOTHERAPY(delayed emesis)
  None
MODERATE RISK OF EMESIS
 PRE-CHEMOTHERAPY
 5HT3 antagonist+ dexamethasone
 5HT3 antagonist+ dexamethasone+ aprepitant
 POST- CHEMOTHERAPY (delayed emesis)
 Aprepitant (days 2 and 3)
 Dexamethasone or 5 HT3 antagonist (days 2-3 or 4)
 Aprepitant (days 2-3, if used pre-chemo) ± dexamethasone (days 2-4) ± lorazepam (days
2-4)

MYELOSUPPRESSION/ BONE MARROW SUPPRESSION

Bone marrow
suppression is a potentially dangerous adverse reaction resulting in decreased
production of blood cells. Bone marrow suppression is manifested by abnormal
laboratory test results and clinical evidence of leukopenia, thrombocytopenia, or
anemia. For example, there is a decrease in the white blood cells or leukocytes
(leukopenia), a decrease in the thrombocytes (thrombocytopenia), and a
decrease in the red blood cells, resulting in anemia. Patients with leukopenia have
a decreased resistance to infection
Manifestations- anemia; thrombocytopenia; neutropenia.

Often managed with delay/ reductionto allow in dose hematopoietic activity to

recover.
Results in low relative dose intensity.
 Highest- Alkylating agents; Antimetabolites; Anthracyclines-
doxorubicin; daunorubicin
 Lowest- Asparginase Bleomycin Vinca alkaloids Hormonal antagonists

Recombinant forms are:
 Granulocyte Colony Stimulating Factor (G-CSF)
 Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
Recombinant human G-CSF- Filgrastim
 Produced in a bacterial expression.
 Non glycosylated peptide of 175 amino acids.
 Molecular weight 18kDa.
Pegfilgrastim-
 Covalent conjugation product of filgrastim and a form of polyethylene glycol.
Lenograstim-
 Glycosylated form of recombinant G-CSF.
Recombinant human GM-CSF- Sargramostim
 Produced in a yeast expression.
 Partially glycosylated peptide of 127 amino acids.
 3 molecular species with molecular weights of 15,500; 15,800; 19,500.

 These preparations have serum half-lives of 2-7 hours.

May be administered Intravenously or subcutaneously.

CHEMOTHERAPY INDUCED THROMBOCYTOPENIA:-

Thrombopoietic growth factors- Interleukin 11; Thrombopoietin.

Interleukin 11-
 Cytokine; Stimulates hematopoiesis, intestinal epithelial cell growth,
osteoclastogenesis; inhibits adipogenesis.
 Enhances megakaryocyte maturation invitro.
 Recombinant human IL-11: Oprelvekin.
 Thrombopoietic response in 5-9 days.
 25-50 µg/kg per day subcutaneously.
 Used in patients undergoing chemotherapy for nonmyeloid malignancy with
severe thrombocytopenia (platelet count 1,00,000 µl.
Anemia occurs as the result of a decreased production of red blood cells in the bone
marrow and is characterized by fatigue, dizziness, shortness of breath, and
palpitations. On occasion, the administration of blood transfusions may be
necessary to correct the anemia.

ALOPECIA.
Alopecia (loss of hair) is a common adverse reaction associated with some of the
antineoplastic drugs. Some drugs cause severe hair loss, whereas others cause
gradual thinning. Examples of drugs commonly associated with severe hair loss are
doxorubicin and vinblastine. Methotrexate, bleomycin, vincristine, and etoposide
are associated with gradual hair loss.
 Begins 1-3 weeks after initiation.
 Scalp- common location
 Hair of beard, eyebrows, eyelashes, axillary and pubic region may be affected.
 Hair loss is reversible.
 Occurs after 3-6 months.
  Permanent alopecia- Rx with busulfan and cyclophosphamide.

Management:-
 SCALP TORNIQUES
 Application of bands around head Pressureoccludes superficial
blood flow to scalpreduces amount of drug delivered to hair follicles.
 Pressure- 10mmHg more than SBP to 300 mmHg.
 5-10 min before or at the time of chemotherapy upto 30 min later.
 SCALP COOLING
 Application of cold to scalp using cap (pre-cooled or exchanges coolant
with reservoir)
 5 min before treatment till an hour later.
 Vasoconstrictionreduces blood flow to scalpreduces amount of drug
available for hair follicle.
 Practically ineffectiveif drug administered as continuous infusion for
long time.
 Increases risk of scalp metastasis
 Hence contraindicated in hematological malignancies and cutaneous T
cell lymphoma
Treatment:-
Minoxidil- a vasodilator
 Prolongs duration of anagen phase.
 Fails to induce significant regrowth of hair in permanent alopecia caused by
busulfan and cyclophosphamide.

MUCOSITIS
• Threatens effectiveness of therapy dose reduction; increases health care cost;
impairs patients quality of life.
• Oral mucositis- a frequent complication of cytoreductive cancer chemotherapy.
• Associated with pain; in neutropenic pts with cancer risk factor for sepsis
Gastrointestinal mucositis injury of rest of alimentary tract.
• Most prominent in small intestine.
Followed by esophagus, stomach, large intestine.
MANAGEMENT OF ORAL MUCOSITIS
• Oral decontamination- antifungal and antibacterial rinses.
• Topical and systemic pain management-
Topical- 2% lidocaine; morphine solution.
Frequent rinsing with NaCl mucosa moist; decreases caking of secretions;
soothes inflamed or ulcerated mucosa.
Cryotherapy with ice chips.
• Palifermin- Keratinocyte Growth Factor.
60 µg/kg/day for 3 days before and after chemotherapy.
Control of bleeding:
• Topical thrombin packs.
• Topical antifibrinolytic agents- tranexamic acid.

Anxiety
Patients and family members are usually devastated by the diagnosis of a
malignancy. The emotional impact of the disease may be forgotten or put aside by
members of the medical team as they plan and institute therapy to control the
disease. Patients undergoing chemotherapy require a great deal of emotional
support from all members of the medical team. Kindness and gentleness in giving
care and an understanding of the strain placed on the patient and the family may
help reduce some of the fear and anxiety experienced during treatment.

DIARRHEA.
Measures to manage diarrhea include a low-residue diet while the bowel rests.
Electrolytes are monitored and supplemented as needed.
Adequate hydration must be maintained; intravenous fluids may be necessary. If
diarrhea is severe, therapy may be delayed or stopped or the dose decreased.

ANOREXIA.
Anorexia (loss of appetite resulting in the inability to eat) is a common occurrence
with the antineoplastic drugs. Is it not uncommon for the patient to report
alterations in the sense of taste during the course of chemotherapy.
Small, frequent meals (five to six meals daily) are usually better tolerated than are
three large meals.
Breakfast is often the best tolerated meal of the day. Stressing the importance of
eating meals high in nutritive value, particularly protein (eg, eggs, milk products,
tuna, beans, peas, and lentils).
Some patients are able to eat high-protein finger foods such as cheese or peanut
butter and crackers. Nutritional supplements may also be prescribed.
If the patient continues to lose weight, a feeding tube may be used to administer
a nutritionally complete liquid. While this is not ideal, the patient who is
malnourished and weak may benefit from this intervention.

Hyperuricaemia
This is secondary to massive cell destruction (uric acid is a product of purine
metabolism) and is especially likely to occur in leukaemias and bulky lymphomas.
Acute renal fai lure, gout and urate stones in the urinary tract may develop.
Allopurinol is protective by decreasing uric acid synthesis.

Gonads
Inhibition of gonadal cells causes oligozoospermia and impotence in males;
inhibition of ovulation and amenorrhoea are common in females.
Damage to the germinal cells may result in mutagenesis.

Foetus
Practically a ll cytotoxic drugs given to pregnant women profoundly damage
the developing foetus. This may lead to abortion, foetal death or teratogenesis.

Educating the Patient and Family

The primary health care provider usually discusses the proposed treatment and
possible adverse drug reactions with the patient and family members
Some of these drugs are taken orally at home. The areas included in a patient and
family teaching plan for this type of treatment regimen are based on the drug
prescribed, the primary health care provider’s explanation of the chemotherapy
regimen and instructions for taking the drug, and the needs of the individual. Some
hospitals or primary health care providers give printed instructions to the patient.

EVALUATION
• The therapeutic effect is achieved.
• Adverse reactions are identified, reported to the primary health care provider,
and managed using nursing interventions.
• Anxiety is reduced.
• The patient verbalizes an understanding of the dosage regimen.
• The patient verbalizes an understanding of treatment modalities and the
importance of continued follow-up care.
• The patient verbalizes the importance of complying with the prescribed
therapeutic regimen.

BREAST CANCER

PATHOPHYSIOLOGY
 Breast cancer is a malignant tumor that starts in the cells of the breast. Like
other cancers, there are several factors that can raise the risk of getting breast
cancer. Damage to the DNA and genetic mutations can lead to breast cancer
 have been experimentally linked to estrogen exposure. Some individuals
inherit defects in the DNA and genes like the BRCA1, BRCA2 and P53 among
others. Those with a family history of ovarian or breast cancer thus are at an
increased risk of breast cancer.
 The immune system normally seeks out cancer cells and cells with damaged
DNA and destroys them. Breast cancer may be a result of failure of such an
effective immune defence and surveillance.
 These are several signalling systems of growth factors and other mediators that
interact between stromal cells and epithelial cells. Disrupting these may lead to
breast cancer as well.

Diagnostic tests and procedures for breast cancer include:

Breast exam
Mammograms
Breast ultrasound Imaging tests
Breast MRI scan
Biopsy
Clinical Breast Breast –
Women in their 20s and 30s should have a clinical breast exam every 3 years.
After age 40, women should have a breast exam every year

Self Exam(CBE) Exam (BSE)

BSE is an option for women starting in their 20s.
Any changes detected should be reported to a medical expert.
BSE: Conducted standing or reclining

Breast imaging techniques:

1. Mammogram:-
An x-ray of the breast.
It uses a very small amount of radiation.
 screening diagnosis
 screening mammograms diagnostic mammogram
A technologist will position your breast for the test.
The breast is pressed between 2 plates to flatten and spread the tissue.
The pressure lasts only a few seconds while the picture is taken.
The breast and plates are repositioned and then
another picture is taken.
The whole process takes about 20 minutes.

2. Breast ultrasound
Uses sound waves to outline a part of the body.
The sound wave echoes are picked up by a computer to create a picture on
a computer screen.
Used to investigate areas of concerns found by a mammogram.
3. Magnetic Resonance Imaging (MRI):-
Use magnets and radio waves.
 Cross-sectional images of the body.
MRI scans can take a long time.
Used if view areas of concern found on a mammogram.
Patients must lie inside a narrow tube, face down on a special platform.
The platform has openings for each breast that allow the image to be taken
without pressing on the breast.
Contrast material may be injected into a vein to help the MRI show more
details.

4. Biopsy:-
A biopsy is done when other tests show that you might have breast cancer.
It confirms if a mass is cancerous or not.
Mass is removed and studied.

Types of BIOPSY Surgical (open) biopsy

Fine needle aspiration (FNA)
biopsy:-
Very fine needle is used.
Extracts fluid from the lump.
Guided by ultrasound.
simple but is not 100%
accurate.
Core needle biopsy
Needle is larger than in fine
needle biopsy.
Removes more tissues.
Clearer results.
Vacuum-assisted biopsies
Done with systems such as
ATEC® (Automated Tissue Excision
and Collection)
Guided by MRI
First the skin is numbed and a
small cut (incision) is made.
A hollow probe is put through
the cut into the breast tissue.
A piece of tissue is sucked out.
Breast cancer grade:
If a biopsy sample is cancer, it is given a grade from 1 to 3.
A lower grade number means a slower-growing cancer, while a higher number
means a fastergrowing cancer.
The grade helps predict the outcome.
Anesthesia is administered.
Incision is made.
Part or whole lump is
extracted and studies.
Lymph node biopsy
Tissues obtained during biopsy are
examined to determine:
Malignant or Benign
Type
Invasive or Non - invasive
Size
Has it metastasized
Is the lymph nodes affected
Treatment
Prognostic Factors considering
during an examination:
Breast cancer grade
Hormone receptor status
HER2/neu status

Hormone receptor status:

Hormone receptors are proteins in cells that can attach to hormones.
Estrogen and progesterone are hormones that fuel breast cancer growth.
 Breast cancers are tested for hormone receptors. If the tumor has them, it is often
called ERpositive, PR positive,
About 2 out of 3 breast cancers have at least one of these receptors.

HER2/neu status:
About 1 out of 5 breast cancers have too much of a protein called HER2/neu.
Tumors with increased levels of HER2/neu are called HER2-positive.
These cancers tend to grow and spread faster than other breast cancers

Staging of breast cancer:-

The TNM staging system
This system takes into account:
the tumor size and spread (T),
whether the cancer has spread to lymph nodes (N) and
whether it has spread to distant organs (M) for metastasis

Sage 0 : Non – Invasive breast cancer. Has not spread to breast tissues.
Stage l : ≤ 2cm and has not spread to lymph nodes.
Stage ll
Stage llA: ≤ 2 cm and has spread to lymph nodes or 2-5 cm and has spread to lymph
nodes.
Stage llB: 2-5 cm and has spread to lymph nodes or > 5 cm and has not spread to
lymph nodes.
Stage lll
Stage lllA: ≤ 5cm and spread to lymph nodes forming clumps or >5 cm and spread
to lymph nodes without forming clumps.
Stage lllB: Any size and spread to the skin or chest wall. Swelling.
Stage lllC: Any size , spread to lymph nodes, skin and chest wall.
Stage lV: Metastasized

TREATMENT OF BREAST CANCER:-

The treatment of breast cancer will depend on various factors:-
The type of breast cancer
The stage and grade of the breast cancer - how large the tumor is, whether or not
it has spread, and if so how far
 Whether or not the cancer cells are sensitive to hormones
The patient's overall health
The age of the patient
The patient's own preferences

The main breast cancer treatment may include:-

Chemotherapy
Surgery
Radiation therapy
Biological therapy (targeted drug therapy)
Hormone therapy

1. CHEMOTHERAPY
Chemotherapy (chemo) is the use of cancer-killing drugs.
Intravenously, given as a shot, or taken as a pill or liquid.
They enter the bloodstream and reach most parts of the body.
Combats metastasis.
Damage some normal cells.
Chemotherapy is a treatment using anticancer (also called cytotoxic) drugs
which aims to destroy cancer cells. It is known as a systemic treatment.
Many different types of chemotherapy drugs are used to treat breast cancer.
They can be given in different ways and in different combinations, according to an
individual’s situation.

1) Intravenous chemotherapy :
The most common way 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 then 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 will usually be on the opposite arm to where you had (or are having)
surgery. This is to avoid the risk of lymphoedema.

2) Oral chemotherapy: This is chemotherapy taken by mouth and it may be

given either as tablets or capsules.

3) Electrochemotherapy : It is a new treatment and is not widely available. It’s

sometimes used to treat breast cancer that has spread to the skin.
Chemotherapy is injected either directly into the area of skin affected or into
the bloodstream. An electric pulse is then used to help the chemotherapy
reach the cancer cells. Once inside the cancer cells, the chemotherapy
destroys them.

HOW CHEMO IS GIVEN? The time between cycles is most

Doctors give chemo in cycles. often 2 or 3 weeks.
 For early-stage breast cancer, the
total course of treatment usually
lasts for 3 to 6 months.
For advanced breast cancer
chemo is often continued as long as
it is working.
The side effects of chemo depend
on:
the type of drugs used
the amount given
and the length of treatment.
Short – term side effects
· Hair loss
· Loss of appetite or increased
appetite
· Nausea and vomiting
· A higher risk of infection (low
WBC count)
· Stopping of menstrual periods
· Easy bruising or bleeding (low
platelets)
· Being very tired
Long - term side effects
Menstrual changes: infertility
Nerve damage: pain, burning or
tingling and
sensitivity to cold or hot.
Heart damage

Adjuvant Chemotherapy
• Early administration of effective combination chemotherapy at a time of
low tumor burden should increase the likelihood of cure and minimize
emergence of drug-resistant tumor cell clones. Combination regimens
have historically been more effective than single agent chemotherapy
• Anthracycline-containing regimens (e.g., doxorubicin and epirubicin)
significantly reduce the rate of recurrence and improve OS 5 and 10 years
after treatment as compared with regimens that contain cyclophosphamide,
methotrexate, and fluorouracil. Both node-negative and nodepositive patients
benefit from anthracycline-containing regimens.
• The addition of taxanes, docetaxel and paclitaxel, a newer class of agents,
to adjuvant regimens comprised of the drugs listed above resulted in
consistently and significantly improved disease-free survival and OS in
node-positive breast cancer patients.
• Chemotherapy should be initiated within 3 weeks of surgical removal of
the primary tumor. The optimal duration of treatment is about 12 to 24 weeks.
• Dose intensity refers to the amount of drug administered per unit of time,
which can be achieved by increasing dose, decreasing time, or both. Dose
density is one way of achieving dose intensity by decreasing time between
treatment cycles.
• Dose-dense regimens may be considered as options for adjuvant therapy
for node-positive breast cancer.
• Increasing doses in standard regimens appears to not be beneficial and
may be harmful.
• Decreasing doses in standard regimens should be avoided unless necessitated
by severe toxicity.
• Short-term toxicities of adjuvant chemotherapy are generally well tolerated,
especially with the availability of serotonin-antagonist and substance
P/neurokinin 1-antagonist antiemetics and colony-stimulating factors.
• Survival benefit for adjuvant chemotherapy in stage I and II breast cancer
is modest. The absolute reduction in mortality at 10 years is 5% in nodenegative
and 10% in node-positive disease.

Adjuvant Biologic Therapy / targeted chemotherapy

Drugs that target HER2
HER2: protein that increase cancer growth.
· Trastuzumab (Herceptin): IV
· Pertuzumab (Perjeta®): IV
· Ado-trastuzumab emtansine (Kadcyla™)
· Lapatinib (Tykerb): pill
• Trastuzumab in combination with adjuvant chemotherapy is indicated in
patients with early stage, HER2-positive breast cancer. The risk of recurrence
was reduced up to 50% in clinical trials.
• Unanswered questions with the use of adjuvant trastuzumab include
optimal concurrent chemotherapy, optimal dose, schedule and duration of
therapy, and use of other concurrent therapeutic modalities
• Trastuzumab, a monoclonal antibody that binds to HER2, produces
response rates of 15% to 20% when used as a single agent and increases
response rates, time to progression, and OS when combined with chemotherapy.
It has been studied in doublet (taxane-trastuzumab; vinorelbinetrastuzumab)
and triplet (trastuzumab-taxane-platinum) combinations
but the optimum regimen is unknown.
• Trastuzumab is well tolerated, but the risk of cardiotoxicity is 5% with
single-agent trastuzumab and unacceptably high in combination with an
anthracycline.
• Lapatinib, a tyrosine kinase inhibitor that targets both HER2 and the
epidermal growth factor receptor, improved response rates and time to
progression in combination with capecitabine, as compared to capecitabine
alone, in patients previously treated with an anthracycline, taxane,
and trastuzumab. The most common adverse events were rash and diarrhea.
• The role of bevacizumab, a monoclonal antibody targeted against vascular
endothelial growth factor, in MBC is currently not clearly defined.

side effects:-
· Mouth sores · Feeling weak or tired
· Diarrhea · Low blood counts
· Nausea · Shortness of breath
· Fatigue · Cough

Common Chemotherapy Regimens for Breast Cancer:-

Adjuvant Chemotherapy Regimens
ACa
Doxorubicin 60 mg/m2 IV, day 1
Cyclophosphamide 600 mg/m2 IV, day 1
Repeat cycles every 21 days for four cycles
AC → Paclitaxel b
Doxorubicin 60 mg/m2 IV, day 1
Cyclophosphamide 600 mg/m2 IV, day 1
Repeat cycles every 21 days for four cycles
Followed by: Paclitaxel 175 mg/m2 IV over 3

FACc
Fluorouracil 500 mg/m2 IV, days 1 and 4
Doxorubicin 50 mg/m2 IV continuous
infusion over 72 hoursv
Cyclophosphamide 500 mg/m2 IV, day 1
Repeat cycles every 21–28 days for six cycles
café
Cyclophosphamide 600 mg/m2 IV, day 1
Doxorubicin 60 mg/m 2 IV bolus, day 1
Fluorouracil 600 mg/m2 IV, day 1
Repeat cycles every 21–28 days for six cycles
FECg
Fluorouracil 500 mg/m2 IV, day 1
Epirubicin 100 mg/m 2 IV bolus, day 1
Cyclophosphamide 500 mg/m2 IV, day 1
Repeat cycle every 21 days for six cycles
CEFj
Cyclophosphamide 75 mg/m2 per day orally
on days 1–14
Epirubicin 60 mg/m2 IV, days 1 and 8
Fluorouracil 600 mg/ IV, days 1 and 8
Repeat cycles every 21 days for six cycles
(requires prophylactic antibiotics or growth
factor support
Metastatic Single-Agent Chemotherapy
Paclitaxell,m
Paclitaxel 175 mg/m2 IV over 3 hours
Repeat cycles every 21 days
Paclitaxel 80 mg/m2 per week IV over 1 hour
Repeat dose every 7 days
Docetaxelo,p
Docetaxel 60–100 mg/m2 IV over 1 hour
Repeat cycles every 21 days
Docetaxel 30–35 mg/m2 per week IV over 30
minutes Repeat dose every 7 days
Capecitabiner
hours Repeat cycles every 21 days for four
cycles
TACd
Docetaxel 75 mg/m2 IV, day 1
Doxorubicin 50 mg/m2 IV bolus, day 1
Cyclophosphamide 500 mg/m2 IV, day 1
(Doxorubicin should be given first)
Repeat cycles every 21 days for six cycles
(must be given with growth factor support)
Paclitaxel → FACf
Paclitaxel 80 mg/m2 per week IV over 1 hour
every
week for 12 weeks
Followed by:
Fluorouracil 500 mg/m2 IV, days 1 and 4
Doxorubicin 50 mg/m2 IV continuous
infusion over 72 hoursv Cyclophosphamide
500 mg/m2 IV, day 1 Repeat cycles every 21–
28 days for four cyclesf
CMFh,i
Cyclophosphamide 100 mg/m2 per day
orally, days 1-14
Methotrexate 40 mg/m2 IV, days 1 and 8
Fluorouracil 600 mg/m2 IV, days 1 and 8
Repeat cycles every 28 days for six cycles or
Cyclophosphamide 600 mg/m2 IV, day 1
Methotrexate 40 mg/m2 IV, day 1
Fluorouracil 600 mg/m2 IV, days 1 and 8
Repeat cycles every 21 days for six cycles
Dose-Dense AC → Paclitaxelk
Doxorubicin 60 mg/m2 IV bolus, day 1
Cyclophosphamide 600 mg/m2 IV, day 1
Repeat cycles every 14 days for four cycles
(must be given with growth factor support)
Followed by: Paclitaxel 175 mg/m2 IV over 3
hours Repeat cycles every 14 days for four
cycles (must be given with growth factor
support)
Vinorelbinen
Vinorelbine 30 mg/m2 IV, days 1 and 8
Repeat cycles every 21 days or or
Vinorelbine 25–30 mg/m2 per week IV
Repeat cycles every 7 days (adjust dose based on
absolute neutrophil count; see product information)
Gemcitabineq
Gemcitabine 600–1,000 mg/m2 per week IV, days 1
8, and 15
or Repeat cycles every 28 days (may need to hold
day 15 dose based on blood counts)q
Liposomal doxorubicins
Capecitabine 2,000–2,500 mg/m2 per day orally, days Liposomal doxorubicin 30–50 mg/m2 IV over
divided twice daily for 14 R 90 minutes
epeat cycles every 21 days Repeat cycles every 28 days

Metastatic Combination Chemotherapy Regimens

Docetaxel + capecitabinet
Docetaxel 75 mg/m2 IV over 1 hour, day
Capecitabine 2,000–2,500 mg/m2 per day orally
divided twice daily for 14 days
Repeat cycles every 21 days
Paclitaxel + Gemcitabineu
1 Paclitaxel 175 mg/m2 IV over 3 hours, day 1
Gemcitabine 1,250 mg/m2 IV days 1 and 8 Repeat
cycles every 21 days

Hormone therapy
Drugs used to block estrogen
Tamoxifen
Toremifene (Fareston®)
Fulvestran
Tamoxifen has been the gold standard for adjuvant endocrine therapy. It
has both estrogenic and antiestrogenic properties, depending on the tissue
and gene in question.
• Tamoxifen 20 mg daily, beginning soon after completing chemotherapy
and continuing for 5 years, reduces the risk of recurrence and mortality.
Tamoxifen is usually well tolerated. Symptoms of estrogen withdrawal
(hot flashes and vaginal bleeding) may occur but decrease in frequency and
intensity over time. Tamoxifen increases the risks of stroke, pulmonary
embolism, deep vein thrombosis, and endometrial cancer, particularly in
women age 50 years or older.

Drugs used to change hormone levels:

Aromatase inhibitors (AIs): stop fat tissue from making estrogen after
menopause
Luteinizing hormone-releasing hormone (LHRH) analogs: shuts down the
ovaries.

• Premenopausal women benefit from ovarian ablation with luteinizing

hormone-releasing hormone (LHRH) agonists (e.g., goserelin) in the
adjuvant setting, either with or without concurrent tamoxifen. Trials are
ongoing to further define the role of LHRH agonists.
• Options for adjuvant hormonal therapy in postmenopausal women
include aromatase inhibitors (e.g. anastrozole, letrozole, or exemestane)
either in place of or after tamoxifen. Adverse effects with aromatase
inhibitors include hot flashes, myalgia/arthralgia, vaginal dryness/atrophy,
mild headaches, and diarrhea.
• The optimal drug, dose, sequence, and duration of administration of
aromatase inhibitors in the adjuvant setting are not known.
Endocrine Therapies Used for Metastatic Breast Cancer

SURGERY
Surgery aims to remove the breast cancer with a margin (border) of normal
tissue to reduce the risk of the cancer coming back in the breast (known as local
recurrence) and to try to stop any spread in the body. The amount of tissue
removed depends on the area of the breast affected and the size of the cancer in
the breast.

TYPES OF SURGERY
1) Breast-conserving surgery
This type of surgery is sometimes called partial (or segmental) mastectomy. It is
also sometimes called lumpectomy or quadrantectomy. In this surgery, only the
part of the breast containing the cancer is removed. The goal is to remove the
cancer as well as some surrounding normal tissue.
 side effects: Include pain, temporary swelling, tenderness, and hard scar tissue
that forms in the surgical site.
As with all operations, bleeding and infection at the surgery site are also
possible.

2) Mastectomy
Mastectomy is surgery to remove the entire breast.
All of the breast tissue is removed, sometimes along with other nearby tissues.

a) Simple mastectomy: Also called total mastectomy, the surgeon removes

the entire breast, including the nipple, but does not remove underarm lymph
nodes or muscle tissue from beneath the breast
b) Skin-sparing mastectomy: In this procedure, most of the skin over the
breast (other than the nipple and areola) is left intact. This approach is only used
when immediate breast reconstruction is planned.
c) Modified radical mastectomy: This procedure is a simple mastectomy
and removal of axillary (underarm) lymph nodes.
d) Radical mastectomy: In this extensive operation, the surgeon removes
the entire breast, axillary lymph nodes, and the pectoral (chest wall) muscles
under the breast.

side effects: wound infection, hematoma (buildup of blood in the wound), and
seroma (buildup of clear fluid in the wound).

3) Lymph node surgery

a) Axillary lymph node dissection (ALND): In this procedure, anywhere
from about 10 to 40 lymph nodes are removed from the area under the arm
(axilla) and checked for cancer spread.
b) Sentinel lymph node biopsy (SLNB): Removes the first lymph node(s) to
which a tumor is likely to spread (these are called the sentinel nodes).
Removing many lymph nodes increases the risk of lymphedema , to lower this
risk, doctors may use a sentinel lymph node biopsy (SLNB).
side effects: As with any operation, pain, swelling, bleeding, and infection are
possible.

4) Reconstructive surgery
• After having a mastectomy (or some breast-conserving surgeries), a woman
might want to consider having the breast mound rebuilt; this is called breast
reconstruction. These procedures are done to restore the breast's appearance
after surgery. Chronic pain after breast surgery
Some women have problems with nerve (neuropathic) pain in the chest wall,
armpit, and/or arm after surgery that doesn’t go away over time. This is called
postmastectomy pain syndrome (PMPS) because it was first described in women
who had mastectomies, but it can also happen after breast-conserving therapy.

RADIATION THERAPY
 Radiation therapy (also called radiotherapy) uses high-energy rays to kill
cancer cells. It affects cells only in the part of the body that is treated with the
radiation. Breast cancer radiation therapy may be used to destroy any remaining
mutated cells that remain in the breast or armpit area after surgery.
Radiation is also used to treat cancer that has spread to other areas, for
example to the bones or brain.
Radiation therapy can be given externally (external beam radiation) or
internally (brachytherapy).
External beam radiation
 This is the most common type of radiation therapy for women with breast
cancer. The radiation is focused from a machine outside the body on the area
affected by the cancer.
 The extent of radiation depends on whether mastectomy or breast-conserving
surgery (BCS) was done and whether or not lymph nodes are involved.
 If mastectomy was done and no lymph nodes had cancer, radiation is targeted at
the chest wall and the places where any drains exited the body.
• If BCS was done, most often the entire breast gets radiation, and an extra
boost of radiation is given to the area in the breast where the cancer was
removed to prevent it from coming back in that area.
• If cancer was found in the lymph nodes under the arm, radiation may b
Internal Radiation
Sometimes called partial-breast radiation or brachytherapy, for use after
lumpectomy. Internal radiation methods typically use small pieces of
radioactive material, called seeds, which are placed in the area around where the
cancer was. The seeds emit radiation into the surrounding tissue. The area that's
very close to the site of the original cancer is the area that is at highest risk of
recurrencence.
TYPES:
1)Interstitial brachytherapy: In this approach, several small, hollow tubes
called catheters are inserted into the breast around the area where the cancer
was removed and are left in place for several days. Radioactive pellets are
inserted into the catheters for short periods of time each day and then removed.
2)Intracavitary brachytherapy: This is the most common type of
brachytherapy. A device is put into the space left from BCS and is left in place
until treatment is complete. There are several different devices that can be used:
MammoSite®, SAVI®, Axxent®, and Contura®.
Mammosite insertion Mammosite tube
SIDE EFFECTS
O Radiation therapy can have side effects, and these vary from person to
person.
O The most common side-effects are:
O Sunburn-type skin irritation of the targeted area (which may range from
mild to intense)
O Red, dry, tender, or itchy skin
O Breast heaviness
O fatigue
 UPPER RESPIRATORY TRACT
INFECTIONS (URTI):-

EPIDEIOLOGY:-
Most common reason for an emergency room /physician office visit.
Occurs in all ages (common between 6 months and 2 yrs of age).
>15 million emergency room and clinic visits annually.
 ~~ 65% recurrence
>80% of patients seen for AOM receive a prescription. Direct and indirect
costs
almost $3 billion annually.

ETIOLOGY:-
~~ 40% to 75% of AOM causes: viral.
Common bacterial pathogens:
Streptococcus pneumoniae (50%),
Non-typeable H. influenzae (30%),
Moraxella catarrhalis (20%).
S. pneumoniae, H. influenzae, and M. catarrhalis can all possess resistance to ß-
lactams.
S. pneumoniae develops resistance through alteration of penicillin-binding
proteins.
H. influenzae and M. catarrhalis produce ß-lactamases
The risk factors for resistance:
Attendance at child care centers.
Antibiotic treatment hx (within the past 30 days).
Age younger than 2 years.

PATHOPHYSIOLGY:-
AOM is caused by an interplay of factors. Usually follows a viral upper
respiratory tract infection
Viral URIs impair eustachian tube function 
Mucosal inflammation,
Impairing mucociliary clearance
– Bacteria that colonize the nasopharynx enter the middle ear and are not
cleared properly.
Promoting bacterial proliferation and infection
Tympanic membrane becomes blocked with fluid, resulting in a bulging and
erythematous ear drum
Children tend to be more susceptible to otitis media than adults
Shorter eustachian tube
More horizontal (facilitating bacterial entry into the middle ear).
– So, it is less functional for middle ear drainage and protection
CLINICAL PRESENTATION
• Acute otitis media presents as an acute onset of signs and symptoms of middle ear
infection such as otalgia, irritability, and tugging on the ear, accompanied by signs
such as a gray, bulging, nonmotile tympanic membrane. These often follow cold
symptoms of runny nose, nasal congestion, or cough
• Resolution of acute otitis media occurs over 1 week. Pain and fever tend to resolve
over 2 to 3 days, with most children becoming asymptomatic at 7 days. Effusions
resolve slowly, 90% have disappeared by 3 months.

General
 The acute onset of signs and symptoms of middle ear infection Following cold
symptoms of runny nose, nasal congestion, or cough.
o Signs and symptoms
 Pain that can be severe (>75% of patients).
 Children may be irritable, tug on the involved ear, and have difficulty sleeping.
 Fever is present in less than 25% of patients and, when present, is more often
in younger children.
 Examination shows a discolored, thickened, bulging eardrum.
 Pneumatic otoscopy or tympanometry demonstrates an immobile eardrum;
50% of cases are bilateral.
 Draining middle ear fluid occurs (<3% of patients) that usually reveals a
bacterial etiology.
o Laboratory tests
o Gram stain, culture, and sensitivities of draining fluid or aspirated fluid if
tympanocentesis is performed.

TREATMENT:-
 The goals of treatment include reduction in signs and symptoms, eradication of
infection, and prevention of complications. Avoidance of unnecessary antibiotic
use is another goal in view of S. pneumoniae.
 Antimicrobial therapy is used to treat otitis media; however, a high percentage of
children will be cured with symptomatic treatment alone. Antibiotic use reduces
the duration of symptoms by about 1 day.
 Delayed antibiotic treatment (48 to 72 hours) may be considered in children 6
months to 2 years of age if symptoms are not severe, as it decreases antibiotic
adverse effects and minimizes bacterial resistance.
 It is difficult to identify who will benefit from antimicrobial therapy. With or
without treatment, about 60% of children who have acute otitis media are
symptom-free within 24 hours.
 Acetaminophen or a nonsteroidal antiinflammatory agent, such as ibuprofen, can
be used to relieve pain and malaise in acute otitis media. Decongestants,
antihistamines, topical corticosteroids, or expectorants have not been proven
effective for acute otitis media.
 Surgical insertion of tympanostomy tubes (T tubes) is an effective method for
the prevention of recurrent otitis media.
 Amoxicillin is the drug of choice for acute otitis media. High-dose amoxicillin (80
to 90 mg/kg/day) is recommended.
 . • If treatment failure occurs with amoxicillin, an agent should be chosen with
activity against β-lactamase–producing H. influenzae and M. catarrhalis as well
as drug-resistant S. pneumoniae (such as high-dose amoxicillin-clavulanate
(recommended), or, cefuroxime, cefdinir, cefpodoxime, cefprozil, or
intramuscular ceftriaxone).
 A metaanalysis reported no difference in cure rates with short (less than 7 days)
and usual durations (at least 7 days) of antibiotic therapy in children. Five to 7
days of therapy may be used in children at least 6 years old who have mild to
moderate acute otitis media.
Antibiotic Prophylaxis of Recurrent Infections
 Recurrent otitis media is defined as at least three episodes in 6 months or at
least four episodes in 12 months. Recurrent infections are of concern because
patients younger than 3 years of age are at high risk for hearing loss and
language and learning disabilities. Data from studies generally do not favor
prophylaxis.
 Vaccination against influenza and pneumococcus may decrease risk of acute
otitis media, especially in those with recurrent episodes. Immunization with the
influenza vaccine reduces the incidence of acute otitis media by 36%.
PHARYNGITIS
Acute infection of the oropharynx or nasopharynx
Inflammation of the throat often caused by infection.
Associated with rare but severe sequelae if not treated appropriately
Non suppurative complications – Acute rheumatic fever, acute
glomerulonephritis, and reactive arthritis
Suppurative complications – Peritonsillar abscess, retropharyngeal abscess,
cervical lymphadenitis, mastoiditis, otitis media, sinusitis, and necrotizing fasciitis

EPIDEMIOLOGY:-
1% to 2% adults visits in and 6% to 8% of pediatric visits
Children ages 5 to 15 years are most susceptible
More common at crowd, institutions areas
Cost ~$1.2 billion total and up to $539 million for children alone

ETIOLOGY:-
 Viral causes: most common.
 Rhinovirus (20%), coronavirus (<5%), adenovirus (5%), HSV(4%),
influenza virus (2%), parainfluenza virus (2%), and EBV(<1%).
 GABHS: primary bacterial cause.
 20% to 30% of cases in children and 5% to 15% of adult infections
 Less common bacterial cause
 Groups C and G Streptococcus, Corynebacterium diphtheriae, N.
gonorrhoeae, Mycoplasma/Chlamydia pneumoniae, Yersinia
enterocolitica
 Mxm not well defined
 If alteration in host immunity (a breach in the pharyngeal mucosa)
 If disruption in mucosal integrity
- Asymptomatic pharyngeal carriers or colonization by GABHS
InfectionInfection
- Pathogenic factors associated with the organism [pyrogenic toxins,
hemolysins, streptokinase, and proteinase] itself play a role

CLINICAL PRESENTATION
• The incubation period is 2 to 5 days, and the illness often occurs in clusters. The
clinical presentation of Group
• Guidelines from the Infectious Disease Society of America, American Academy of
Pediatrics, and the American Heart Association suggest that testing for Group A
Streptococcus be done in all patients with signs and symptoms. Only those with a
positive test for Group A Streptococcus require antibiotic treatment.
Clinical Presentation and Diagnosis of Group A Streptococcal Pharyngitis
General:- A sore throat of sudden onset that is mostly self-limited. Fever and
constitutional symptoms resolving in about 3–5 days.
Clinical signs and symptoms are similar for viral causes as well as nonstreptococcal
bacterial causes.
Signs and symptoms
Sore throat.
Pain on swallowing.
Fever.
Headache, nausea, vomiting, and abdominal pain (especially children).
Erythema/inflammation of the tonsils and pharynx with or without patchy
exudates.
Enlarged, tender lymph nodes.
Red swollen uvula, petechiae on the soft palate, and a scarlatiniform rash.
Several symptoms that are not suggestive of Group A Streptococcus are cough,
conjunctivitis, coryza, and diarrhea.

Laboratory tests Throat swab and culture or rapid antigen detection testing.

TREATMENT
• The goals of treatment of pharyngitis are to improve clinical signs and symptoms,
minimize adverse drug reactions, prevent transmission to close contacts, and
prevent acute rheumatic fever and suppurative complications such as peritonsillar
abscess, cervical lymphadenitis, and mastoiditis.
• Antimicrobial therapy should be limited to those who have clinical and
epidemiologic features of Group A streptococcal pharyngitis with a positive
laboratory test.
• As pain is often the primary reason for visiting a physician, emphasis on
analgesics such as acetaminophen and nonsteroidal antiinflammatory drugs to aid
in pain relief is strongly recommended. However, acetaminophen is a better option
because there is some concern that nonsteroidal antiinflammatory drugs may
increase the risk for necrotizing fasciitis or toxic shock syndrome. Either systemic
or topical analgesics can be used, as well as antipyretics and other supportive care
including rest, fluids, lozenges, and saltwater gargles.
• Antimicrobial treatment should be limited to those who have clinical and
epidemiologic features of Group A streptococcal pharyngitis with a positive
laboratory test. Penicillin is the drug of choice in the treatment of Group A
streptococcal pharyngitis
• In patients allergic to penicillin, a macrolide such as erythromycin or a first-
generation cephalosporin such as cephalexin (if the reaction is nonimmunoglobulin
E–mediated hypersensitivity) can be used. Newer macrolides such as azithromycin
and clarithromycin are as effective as erythromycin and cause fewer GI adverse
effects.
• If patients are unable to take oral medications, intramuscular benzathine
penicillin can be given although it is painful and no longer available in Canada.
• The duration of therapy for Group A streptococcal pharyngitis is 10 days to
maximize bacterial eradication.

Dosing Guidelines for Pharyngitis

Antibiotics and Dosing for Recurrent Episodes of Pharyngitis

Paranasal sinuses (“the sinuses”) are air-filled cavities located within the bones of
the face and around the nasal cavity and eyes.
Each sinus is named for the bone in which it is located:
Maxillary sinus
Ethmoid sinus
Frontal sinus
Sphenoid sinu
 The pink membranes lining the sinuses make mucus that is cleared out of the
sinus cavities and drains into the nasal passage.
 Both airflow & mucus ends up in a part of throat [nasopharynx] Air is then
breathed into the windpipe and lungs, while the mucus is swallowed
 Other structures associated with the nasal and sinus tract:
  Tear duct (nasolacrimal duct): drains tears from the inside corner of the
eye into the nasal cavity
 Eustachian tube: responsible for clearing air pressure in the ears; it opens
into the back of the sidewall of the nasopharynx.
 Adenoids: collection of tonsil-like tissue [at top of the nasopharynx]

TREATMENT
• The goals of treatment of acute sinusitis are the reduction in signs and symptoms,
achieving and maintaining patency of the ostia, limiting antimi crobial treatment to
those who may benefit, eradication of bacterial infection with appropriate
antimicrobial therapy, minimizing the duration of illness, prevention of
complications, and prevention of progression from acute disease to chronic disease.
• Approximately 65% of patients with acute sinusitis will recover spontaneously
(these are likely patients with viral sinusitis).

• Nasal decongestant sprays such as phenylephrine and oxymetazoline that reduce

inflammation by vasoconstriction are often used in sinusitis. Use should be limited
to the recommended duration of the product to prevent rebound congestion. Oral
decongestants may also aid in nasal or sinus patency. To reduce mucociliary
function, irrigation of the nasal cavity with saline and steam inhalation may be used
to increase mucosal moisture, and mucolytics (e.g., guaifenesin) may be used to
decrease the viscosity of nasal secretions. Antihistamines should not be used for
acute bacterial sinusitis in view of their anticholinergic effects that can dry mucosa
and disturb clearance of mucosal secretions.
• Antimicrobial therapy is superior to placebo in reducing or eliminating symptoms,
although the benefit is small.
• Amoxicillin is first-line treatment for acute bacterial sinusitis. It is cost effective in
acute uncomplicated disease, and initial use of newer broadspectrum agents is not
justified.
• The current recommendations are 10 to 14 days, or at least 7 days, of
antimicrobial therapy after signs and symptoms are under control.