LAB E and F

UNIT 4: PHARMACOTHERAPY OF ONCOLOGIC DISODERS

TOPIC: PROSTATE CANCER
A. GENERAL PATHOPHYSIOLOGY WITH DIAGRAM

The prostate gland is a solid, rounded, heart-shaped organ positioned between the neck of the bladder and the urogenital diaphragm.
Normal growth and differentiation of the prostate depends on the presence of androgens, specifically DHT. The testes and the
adrenal glands are the major sources of circulating androgens. Hormonal regulation of androgen synthesis is mediated through a
series of biochemical interactions between the hypothalamus, pituitary, adrenal glands, and testes. Luteinizing hormone-releasing
hormone (LHRH) released from the hypothalamus stimulates the release of luteinizing hormone (LH) and follicle stimulating
hormone (FSH) from the anterior pituitary gland. LH complexes with receptors on the Leydig cell testicular membrane and
stimulates the production of testosterone and small amounts of estrogen. FSH acts on the Sertoli cells within the testes to promote
the maturation of LH receptors and to produce an androgen-binding protein. Circulating testosterone and estradiol influence the
synthesis of LHRH, LH, and FSH by a negative feedback loop operating at the hypothalamic and pituitary level. Prolactin, growth
hormone, and estradiol appear to be important accessory regulators for prostatic tissue permeability, receptor binding, and
testosterone synthesis.

B. FACTORS THAT INDUCE OF POTENTIATE THE DISEASE

 Age Prostate cancer is rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50.
About 6 in 10 cases of prostate cancer are found in men older than 65.

 Race/ethnicity Prostate cancer develops more often in African-American men and in Caribbean men of African ancestry
than in men of other races. And when it does develop in these men, they tend to be younger. Prostate cancer occurs less
often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. The reasons for these racial and ethnic
differences are not clear.

 Geography Prostate cancer is most common in North America, northwestern Europe, Australia, and on Caribbean islands.
 It is less common in Asia, Africa, Central America, and South America.

 Diet A number of epidemiologic studies support an association between high fat intake and risk of prostate cancer. A
strong correlation between national per capita fat consumption and prostate cancer mortality has been reported, and
prospective case-control studies suggest that a high-fat diet is associated with a two-fold higher risk of prostate cancer.

 Family history Prostate cancer seems to run in some families, which suggests that in some cases there may be an inherited
or genetic factor. Still, most prostate cancers occur in men without a family history of it.

 Gene changes Several inherited gene changes (mutations) seem to raise prostate cancer risk, but they probably account for
only a small percentage of cases overall. For example:

o Inherited mutations of the BRCA1 or BRCA2 genes, which are linked to an increased risk of breast and ovarian
cancers in some families, can also increase prostate cancer risk in men (especially mutations in BRCA2).
o Men with Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), a
condition caused by inherited gene changes, have an increased risk for a number of cancers, including prostate
cancer.

C. CLINICAL PRESENTATION

 Locally Invasive Disease

■ Ureteral dysfunction, frequency, hesitancy, and dribbling
■ Impotence

 Advanced Disease
■ Back pain
■ Cord compression
■ Lower-extremity edema
■ Pathologic fractures
■ Anemia
■ Weight loss

D. LABORATORY DIAGNOSTIC TEST/S

The common approach to prostate cancer screening, as recommended by the American Cancer Society, is to offer a baseline PSA
and digital rectal examination (DRE) beginning at age 50 years to all men of normal risk with a 10-year or greater life expectancy.
Men at high risk (African American men and men with a strong family of one or more first-degree relatives), should begin testing
at age 45 years. Men at even higher risk, secondary to multiple first-degree relatives affected at an early age, could begin testing at
age 40 years.

 Digital rectal exam (DRE). During a DRE, your doctor inserts a gloved, lubricated finger into your rectum to examine
your prostate, which is adjacent to the rectum. If your doctor finds any abnormalities in the texture, shape or size of the
gland, you may need further tests.

 Prostate-specific antigen (PSA) test. A blood sample is drawn from a vein in your arm and analyzed for PSA, a
substance that's naturally produced by your prostate gland. It's normal for a small amount of PSA to be in your
bloodstream. However, if a higher than usual level is found, it may indicate prostate infection, inflammation, enlargement
or cancer.

 Ultrasound. During a transrectal ultrasound, a small probe, about the size and shape of a cigar, is inserted into your
rectum. The probe uses sound waves to create a picture of your prostate gland.

 Magnetic resonance imaging (MRI). In some situations, your doctor may recommend an MRI scan of the prostate to
create a more detailed picture. MRI images may help your doctor plan a procedure to remove prostate tissue samples.

 Collecting a sample of prostate tissue. To determine whether there are cancer cells in the prostate, your doctor may
recommend a procedure to collect a sample of cells from your prostate (prostate biopsy). Prostate biopsy is often done
using a thin needle that's inserted into the prostate to collect tissue. The tissue sample is analyzed in a lab to determine
whether cancer cells are present.
Determining whether prostate cancer is aggressive

When a biopsy confirms the presence of cancer, the next step is to determine the level of aggressiveness (grade) of the cancer cells.
A doctor in a lab examines a sample of your cancer cells to determine how much cancer cells differ from the healthy cells. A higher
grade indicates a more aggressive cancer that is more likely to spread quickly.

Techniques used to determine the aggressiveness of the cancer include:

 Gleason score. The most common scale used to evaluate the grade of prostate cancer cells is called a Gleason score.
Gleason scoring combines two numbers and can range from 2 (nonaggressive cancer) to 10 (very aggressive cancer), though
the lower part of the range isn't used as often.

Most Gleason scores used to assess prostate biopsy samples range from 6 to 10. A score of 6 indicates a low-grade prostate
cancer. A score of 7 indicates a medium-grade prostate cancer. Scores from 8 to 10 indicate high-grade cancers.

 Genomic testing. Genomic testing analyzes your prostate cancer cells to determine which gene mutations are present.
This type of test can give you more information about your prognosis. But it's not clear who might benefit most from this
information, so the tests aren't widely used. Genomic tests aren't necessary for every person with prostate cancer, but they
might provide more information for making treatment decisions in certain situations.

Determining whether the cancer has spread

Once a prostate cancer diagnosis has been made, your doctor works to determine the extent (stage) of the cancer. If your doctor
suspects your cancer may have spread beyond your prostate, one or more of the following imaging tests may be recommended:

 Bone scan
 Ultrasound
 Computerized tomography (CT) scan
 Magnetic resonance imaging (MRI)
 Positron emission tomography (PET) scan

E. GOALS OF THERAPY

 Provide each man with the best quality and length of life possible as if the prostate cancer had never developed in the first
place.
 keep the cancer under control for as long as possible
 Minimize morbidity and mortality caused by prostate cancer while minimizing toxicity associated with prostate cancer
treatments.
 Eradicating known tumors entirely
 Preventing the recurrence or spread of the primary cancer
 Relieving symptoms if all reasonable curative approaches have been exhausted.

F. THERAPEUTIC OPTIONS

FIRST LINE TREATMENT SECOND-LINE TREATMENT

Luteinizing Hormone-Releasing Hormone Agonists LHRH
agonists are a reversible method of androgen ablation and are as
effective as orchiectomy in treating prostate cancer. Currently
available LHRH agonists include leuprolide, leuprolide depot,
leuprolide implant, triptorelin depot, triptorelin implant, and
goserelin acetate implant.
Secondary Hormonal Manipulations
Secondary hormonal manipulations, such as the addition of
an antiandrogen to a patient who incompletely suppresses
testosterone secretion with an LHRH agonist, or withdrawal
of antiandrogens in a patient receiving combination therapy,
or use of agents that inhibit androgen synthesis, can be
attempted in patients initially treated with one hormonal
modality. Supportive care, chemotherapy, or local
radiotherapy can be used in patients who have failed all
forms of androgen-ablation manipulations because these
patients are considered to have androgen-independent
 disease

Antiandrogen
Three antiandrogens—bicalutamide, nilutamide, and flutamide
—are currently available. Antiandrogens have been used as
monotherapy in previously untreated patients, but a recent meta-
analysis determined that patients who received monotherapy with
antiandrogens have a shorter survival than patients treated with
LHRH agonist therapy
Combined Hormonal Blockade
Although up to 80% of patients with advanced prostate cancer
will respond to initial hormonal manipulation, nearly all patients
will progress within 2 to 4 years after initiating therapy. Two
mechanisms have been proposed to explain this tumor resistance.
The tumor could be heterogeneously composed of cells that are
hormone dependent and hormone independent, or the tumor
could be stimulated by extratesticular androgens that are
converted intracellularly to DHT. The rationale for combination
hormonal therapy is to interfere with multiple hormonal
pathways to completely eliminate androgen action. In clinical
trials, combination hormonal therapy, sometimes also referred to
as maximal androgen deprivation or total androgen blockade, has
been used. The combination of LHRH agonists or orchiectomy
with antiandrogens is the most extensively studied combined
androgen-deprivation approach.

G. DRUG MONITORING PARAMETERS

SUBJECTIVE- OBJECTIVE SUBJECTIVE-TOXIC OBJECTIVE-TOXIC

THERAPEUTIC THERAPEUTIC
Relief of signs and symptoms Decreased tumor size Signs and symptoms becomes Enlarged tumor
Better quality of life No lymph nodes worse
Positive response of tumor
markers
UNIT 4: PHARMACOTHERAPY OF ONCOLOGIC DISODERS
TOPIC: CERVICAL CANCER
A. GENERAL PATHOPHYSIOLOGY WITH DIAGRAM

HPV is the causative agent in cervical cancer. More than 75 percent of cases are due to high-risk HPV 16 and 18. Although there
are more than a half-million cases of HPV identified annually, most are low-grade infections and will spontaneously resolve within
two years. Central to the development of cervical cancer is infection with HPV with the two major risk factors being chronic
infection with high-risk HPV (HR HPV) and ineffective clearance of the virus. While 90% of HPV infections in women clear on
their own within a few months or years, research has shown that HR HPV modifies genome sequences affecting the woman’s
physiology leading to distinct clinical presentations. Cytology exams have shown low-grade squamous intraepithelial lesions up to
two years after the clearance of the infection in some women. The process of the transformation of a cell infected with HPV to a
cancer cell is very complex and described in basic terms involves the infection of basal cells found  “between the squamous
epithelium of the ectocervix and the columnar epithelium of the endocervix.". Viral replication occurs within the epithelial cell
during its differentiation cycle where genes coding for viral replication factors are dispatched. The differentiation cycle is required
for the production of viral particles on the top of the squamous epithelium. Finally, HPV DNA replication begins when the basal
cell DNA is duplicated.

B. FACTORS THAT INDUCE OF POTENTIATE THE DISEASE

 Human papillomavirus (HPV) infection. The most important risk factor for cervical cancer is infection with HPV.
HPV is common. Most people become infected with HPV when they become sexually active, and most people clear
the virus without problems. There are over 100 different types of HPV. Not all of them are linked to cancer. The
HPV types, or strains, that are most frequently associated with cervical cancer are HPV16 and HPV18. Starting to
have sex at an earlier age or having multiple sexual partners puts a person at higher risk of being infected with high-
risk HPV types.

 Immune system deficiency. People with lowered immune systems have a higher risk of developing cervical cancer.
A lowered immune system can be caused by immune suppression from corticosteroid medications, organ
transplantation, treatments for other types of cancer, or from the human immunodeficiency virus (HIV), which is
the virus that causes acquired immune deficiency syndrome (AIDS). When a person has HIV, their immune system is
less able to fight off early cancer.
 Herpes. Women who have genital herpes have a higher risk of developing cervical cancer.

 Smoking. Women who smoke are about twice as likely to develop cervical cancer as women who do not smoke.

 Age. People younger than 20 years old rarely develop cervical cancer. The risk goes up between the late teens and
mid-30s. Women past this age group remain at risk and need to have regular cervical cancer screenings, which
include a Pap test and/or an HPV test.

 Socioeconomic factors. Cervical cancer is more common among groups of women who are less likely to have access
to screening for cervical cancer. Those populations are more likely to include Black women, Hispanic women,
American Indian women, and women from low-income households.

 Oral contraceptives. Some research studies suggest that oral contraceptives, which are birth control pills, may be
associated with an increased risk of cervical cancer and may be associated with higher-risk sexual behavior.
However, more research is needed to understand how oral contraceptive use and the development of cervical cancer
are connected.

 Exposure to diethylstilbestrol (DES). Women whose mothers were given this drug during pregnancy to prevent
miscarriage have an increased risk of developing a rare type of cancer of the cervix or vagina. DES was given for this
purpose from about 1940 to 1970. Women exposed to DES should have an annual pelvic examination that includes a
cervical Pap test as well as a 4-quadrant Pap test, in which samples of cells are taken from all sides of the vagina to
check for abnormal cells.

C. CLINICAL PRESENTATION

 Blood spots or light bleeding between or following periods

 Menstrual bleeding that is longer and heavier than usual
 Bleeding after intercourse, douching, or a pelvic examination
 Increased vaginal discharge
 Pain during sexual intercourse
 Bleeding after menopause
 Unexplained, persistent pelvic and/or back pain
 Swelling of the legs
 Problems urinating or having a bowel movement
 Blood in the urine

D. LABORATORY DIAGNOSTIC TEST/S

 Physical exam and health history: An exam of the body to check general signs of health, including checking for signs of
disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and
treatments will also be taken.

 Pelvic exam: An exam of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. A speculum is inserted into the
vagina and the doctor or nurse looks at the vagina and cervix for signs of disease. A Pap test of the cervix is usually done.
The doctor or nurse also inserts one or two lubricated, gloved fingers of one hand into the vagina and places the other
hand over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. The doctor or nurse also
inserts a lubricated, gloved finger into the rectum to feel for lumps or abnormal areas.
 Pap test: A procedure to collect cells from the surface of the cervix and vagina. A piece of cotton, a brush, or a small
wooden stick is used to gently scrape cells from the cervix and vagina. The cells are viewed under a microscope to find
out if they are abnormal. This procedure is also called a Pap smear.

 Human papillomavirus (HPV) test: A laboratory test used to check DNA or RNA for certain types of HPV infection.
Cells are collected from the cervix and DNA or RNA from the cells is checked to find out if an infection is caused by a
type of HPV that is linked to cervical cancer. This test may be done using the sample of cells removed during a Pap test.
This test may also be done if the results of a Pap test show certain abnormal cervical cells.

 Endocervical curettage: A procedure to collect cells or tissue from the cervical canal using a curette (spoon-shaped
instrument). Tissue samples are taken and checked under a microscope for signs of cancer. This procedure is sometimes
done at the same time as a colposcopy.

 Colposcopy: A procedure in which a colposcope (a lighted, magnifying instrument) is used to check the vagina and cervix
for abnormal areas. Tissue samples may be taken using a curette (spoon-shaped instrument) or a brush and checked under
a microscope for signs of disease.

 Biopsy: If abnormal cells are found in a Pap test, the doctor may do a biopsy. A sample of tissue is cut from the cervix and
viewed under a microscope by a pathologist to check for signs of cancer. A biopsy that removes only a small amount of
tissue is usually done in the doctor’s office. A woman may need to go to a hospital for a cervical cone biopsy (removal of
a larger, cone-shaped sample of cervical tissue).

E. GOALS OF THERAPY

 Relieve signs and symptoms caused by cervical cancer

 Eradicate known tumors
 Provide an effective therapy while minimizing risk of treatment
  Improve the quality of life of the patient
 Prolong life of patient for as long as possible

F. THERAPEUTIC OPTIONS

Five types of standard treatment are used:

Surgery
Surgery (removing the cancer in an operation) is sometimes used to treat cervical cancer. The following surgical procedures may be
used:
 Conization: A procedure to remove a cone-shaped piece of tissue from the cervix and cervical canal. A pathologist views
the tissue under a microscope to look for cancer cells. Conization may be used to diagnose or treat a cervical condition. This
procedure is also called a cone biopsy.

Conization may be done using one of the following procedures:

o Cold-knife conization: A surgical procedure that uses a scalpel (sharp knife) to remove abnormal tissue or cancer.
o Loop electrosurgical excision procedure (LEEP): A surgical procedure that uses electrical current passed through
a thin wire loop as a knife to remove abnormal tissue or cancer.
o Laser surgery: A surgical procedure that uses a laser beam (a narrow beam of intense light) as a knife to make
bloodless cuts in tissue or to remove a surface lesion such as a tumor.

The type of conization procedure used depends on where the cancer cells are in the cervix and the type of cervical cancer.

 Total hysterectomy: Surgery to remove the uterus, including the cervix. If the uterus and cervix are taken out through
the vagina, the operation is called a vaginal hysterectomy. If the uterus and cervix are taken out through a large incision (cut)
in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a small
incision in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy

 Radical hysterectomy: Surgery to remove the uterus, cervix, part of the vagina, and a wide area of ligaments and tissues
around these organs. The ovaries, fallopian tubes, or nearby lymph nodes may also be removed.
 Modified radical hysterectomy: Surgery to remove the uterus, cervix, upper part of the vagina, and ligaments and tissues
that closely surround these organs. Nearby lymph nodes may also be removed. In this type of surgery, not as many tissues
and/or organs are removed as in a radical hysterectomy.
 Radical trachelectomy: Surgery to remove the cervix, nearby tissue and lymph nodes, and the upper part of the vagina. The
uterus and ovaries are not removed.
 Bilateral salpingo-oophorectomy: Surgery to remove both ovaries and both fallopian tubes.
 Pelvic exenteration: Surgery to remove the lower colon, rectum, and bladder. The cervix, vagina, ovaries, and nearby
lymph nodes are also removed. Artificial openings (stoma) are made for urine and stool to flow from the body to a collection
bag. Plastic surgery may be needed to make an artificial vagina after this operation.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them
from growing. There are two types of radiation therapy:
 External radiation therapy uses a machine outside the body to send radiation toward the cancer. Certain ways of giving
radiation therapy can help keep radiation from damaging nearby healthy tissue. This type of radiation therapy includes the
following:
o Intensity-modulated radiation therapy (IMRT): IMRT is a type of 3-dimensional (3-D) radiation therapy that uses
a computer to make pictures of the size and shape of the tumor. Thin beams of radiation of different intensities
(strengths) are aimed at the tumor from many angles.
 Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly
into or near the cancer.
The way the radiation therapy is given depends on the type and stage of the cancer being treated. External and internal radiation
therapy are used to treat cervical cancer, and may also be used as palliative therapy to relieve symptoms and improve quality of life.

Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them
from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can
reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal
fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).
The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Targeted therapy
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without
harming normal cells.
Monoclonal antibody therapy is a type of targeted therapy that uses antibodies made in the laboratory from a single type of immune
system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The
antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal
antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.
Bevacizumab is a monoclonal antibody that binds to a protein called vascular endothelial growth factor (VEGF) and may prevent
the growth of new blood vessels that tumors need to grow. Bevacizumab is used to treat cervical cancer that
has metastasized (spread to other parts of the body) and recurrent cervical cancer.

Immunotherapy
Immunotherapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a
laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called
biotherapy or biologic therapy.
Immune checkpoint inhibitor therapy is a type of immunotherapy.
 Immune checkpoint inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body’s immune
responses in check. When PD-1 attaches to another protein called PDL-1 on a cancer cell, it stops the T cell from killing the
cancer cell. PD-1 inhibitors attach to PDL-1 and allow the T cells to kill cancer cells. Pembrolizumab is a type of immune
checkpoint inhibitor used to treat recurrent cervical cancer.

G. DRUG MONITORING PARAMETERS

SUBJECTIVE- OBJECTIVE SUBJECTIVE-TOXIC OBJECTIVE-TOXIC

THERAPEUTIC THERAPEUTIC
Relief of signs and symptoms Positive response to treatment Signs and symptoms becomes Cancer have spread
Better quality of life worse

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