Republic of the Philippines

UNIVERSITY OF NORTHERN PHILIPPINES

Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986

Chapter III: TREATMENT MODALITIES

Introduction:
Cancer is a global issue majorly affecting developing countries. According to a survey,
63% of deaths due to cancer are reported in developing countries. There are different conventional
treatment modalities that are available to treat and manage cancer. However, new cancer treatment
options are being explored continuously as over 60% of all current experimental trials worldwide
are focusing on tumor cures. The success of treatment depends upon the type of cancer, the locality
of the tumor, and its stage of progression. Surgery, radiation-based surgical knives, chemotherapy,
and radiotherapy are some of the traditional and most widely used treatment options. Some of the
modern modalities include hormone-based therapy, anti-angiogenic modalities, stem cell
therapies, and dendritic cell-based immunotherapy.
This chapter discusses different traditional and novel treatment modalities to combat
different types of cancer.
❖ Cancer Prevalence
Cancer is the principal cause of death equally in developed and underdeveloped countries
but is more prevalent in middle-income countries, probably due to prevailing poor socioeconomic
conditions. The geographic differences in the prevalence of cancer can be explained by many
contributing factors, like early diagnosis, age factor, the occurrence of risk factors, screening tests,
and accessibility of quality treatment. According to the report of IARC (International Agency for
Research on Cancer), 14.1 million cases of cancer were reported in 2012 globally, of which 8
million were reported from underdeveloped countries which are about 82% of the total population
of the world.
❖ Cancer treatment modalities
Since the recognition of the malignancy, the objective of extraordinary research is to
discover novel methods of quality treatment approaches for cancer. Over 60% of all ongoing
medical quality treatment trials worldwide concentrate on cancer. The selection of treatment and
its progress depends on the type of cancer, its locality, and its stage of progression. Surgery,
radiation-based surgical knives, chemotherapy, and radiotherapy are some of the traditional and
most widely used treatment methods. Some of the modern modalities include hormone-based
therapy, anti-angiogenic modalities, stem cell therapies, immunotherapy, and dendritic cell-based
immunotherapy. Side effects associated with traditional methods of cancer treatment highlight the
scope of novel cancer treatment methods. Different novel treatment systems utilized for the
treatment of malignancy include treatment against the angiogenic ability of cancers, oncolytic
virotherapy, hereditary control of apoptotic and tumor-attacking pathways, antisense, and RNAi

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
techniques. These treatments are employed against cancer of the cerebrum, prostate, lung, breast,
colorectal, pancreatic, liver, head and neck, bladder, skin, ovarian, and renal malignancy.
A. Surgical removal of tumors
Surgery, resection, or operation is thought of as one of the most promising and conventional
treatments for many benign and malignant tumors as it assures the least damage to the surrounding
tissues as compared to chemotherapy and radiotherapy. Another reason for considering surgery as
the preferred treatment option is that the tumor can be removed without the unnecessary risk of
tissue damage. Different kinds of surgeries either open or minimally invasive can be performed
depending on various factors:
• The reason for the surgery
• The part of the body where surgery is to be performed
• The mass of the tumor to be removed
• Patient’s preference
Surgeries also vary depending on the stage of cancer. Surgery may:
• Remove the entire tumor from a certain part
• Debulk a tumor in case its removal may cause damage to a certain organ
• Ease cancer symptoms in cases when a large tumor is causing pain or intense pressure on
any body part
In the case of open surgery, one large cut is made, and it usually results in the removal of the
tumor along with some amount of healthy tissues associated with some closely present lymph
nodes. In contrast, for minimally invasive surgery, the surgeon makes a few small cuts instead of
one large one and then with the aid of a laparoscope which is a thin tube with a camera attached
to it views the tumor in detail. The camera shows the image on a screen which helps the surgeon
to monitor his activity. The tumor, along with a small number of healthy tissues, is then carefully
removed with the assistance of specialized surgery tools.
❖ Radiation-based surgical knife

a. Stereotactic radiosurgery (SRS)

Stereotactic radiosurgery (SRS) is a kind of therapeutic radiology in which ionizing
radiations are used for the damage and destruction of selected areas within an organ or tissue.
This technique exposes a small area of the body to a very high dose of radiation. However, no
cutting or blade is used in the entire process, but it is still called surgery because the results of

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
this treatment are quite similar to an ordinary surgery. As the beam of radiation administered
is of a very high dose, it is very important that the beam of radiation is highly focused so that
the peripheral tissues are left unaffected. It is primarily utilized in cases of brain tumors at
locations where conventional surgical techniques are hard or unsafe to use or in other cases
when the health status of a patient does not support him to tolerate a surgical procedure.

b. Gamma knife systems

A Gamma Knife technique does not include real surgery, nor is the Gamma Knife
actually a blade. It utilizes light emissions and centered gamma beams to treat little to medium-
sized sores and tumors. Many radiation beams combine to concentrate on the cell mass under
treatment, giving an exceptionally high dose of radiation without a surgical cut or opening.

B. Radiation therapy

✓ Principles of radiation therapy

Radiation in cancer therapy can be described as a physical entity used to kill cancer
cells. The kind of radiation used in therapy is ionizing radiation. The radiation upon
incidence causes particles in biological bodies to charge electrically; thus, the term is
“ionizing,” and energy is transferred in this way from the rays to the cells of the body
through which it passes. This energy can either directly kill cancer cells or genetically alter
them so that they accede to apoptosis and cell death.

The mechanism underlying genetic alterations in cells treated with radiation lies in
the fact that the damaged DNA is unable to replicate and thus cell division is halted, which
in turn causes cells to die. The adverse effect of radiation therapy is that it also hits normal
cells lying in the peripheries of the main tumorous mass. However, improved imaging
techniques and attempts at accurate targeting of the cancer mass in addition to the normal
cells’ ability to regain normal function faster than cancer cells as cancer cells lack efficient
repair systems minimize the net damage done by radiation.

✓ Radiation therapy techniques:

1. Fractionation

Fractionated delivery of radiation therapy employs the radiobiological difference

between normal and cancer cells, multiplying the survival edge of normal cells over cancer
cells, by many folds, since they have an intact repair system triggered by sublethal dosages
of radiation.

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
2. 3D conformal radiotherapy (3DCRT)

The usage of 2D rectangular fields in therapy has become obsolete, making CT

scan-based 3D radiation therapy the primary method for the detection of cancer masses,
avoidance of vital organs, and target selection for radiation therapy.

3. Intensity-modulated radiation therapy (IMRT)

This technology uses inverse planning software, which modulates the intensity of
radiation beams used during therapy, resulting in an irregularity of radiation dosages that
differentially target tumors as opposed to vital organs.

4. Image-guided radiotherapy (IGRT)

Using imaging techniques before therapy, such as IGRT, helps position radiation
correctly, diverting rays away from critical organs, targeting only tumor masses, and
consequently reducing organ damage as a result of errors in aiming (Figure 2).

Figure 2.

Direct and
indirect
mechanisms of
radiotherapy-
based treatments.

C. Chemotherapy

Chemotherapy halts tumor progression by killing off its ability to divide and enforcing
apoptosis. Normal biological functioning of the body refreshes cells of the body by removing
excess cells or damaged cells and thus signaling new cell formation. In contrast, tumor cells have
an increased capacity to divide and the quality of immortality as they are not controlled by
apoptosis. Therefore, where in normal bodies the cell proliferation is balanced by cell death and is
regulated, in cancerous masses, the cell proliferation to cell death ratio is high. Chemotherapy acts
here to bring about changes in the tumor cells so that they stop growing or dying; thus, the two
branches of chemotherapeutic drugs are cytostatic (biological drugs) and cytotoxic, respectively.

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
However, chemotherapeutic drugs also target normal cells, which could result in a variety
of side effects depending on the dosage such as hair loss, nausea, fatigue, vomiting, etc. As a result
of vigorous chemotherapy treatment, patients become immunocompromised; this can result in
complicated infections and consequently death. Out of the chemotherapeutic drugs discovered, a
total of 132 are FDA approved. These drugs are designed to specifically target tumor cells and kill
them by genotoxic effect, i.e., the production of reactive oxygen species. However, to some extent,
these drugs also affect normal cells of the body.

The use of chemotherapy as a treatment for cancer started at the beginning of the twentieth
century. The effects of drugs studied in four programs conducted in World War II were the
leverage over which a national effort to develop drugs was initiated in 1955, known as Cancer
Chemotherapy National Service Center. Two diseases, acute childhood leukemia and advanced
Hodgkin’s disease cured using combination chemotherapy in the 1960s and 1970s, respectively,
lead to acceptance of the ability of drugs to cure complicated cancers. This also encouraged studies
on adjuvant chemotherapy with the aid oa f national cancer program. Molecular studies on
abnormalities in cancer cells are an important screening process today for checking the
effectiveness of new drugs and designing targeted therapies. This has advanced chemotherapy
today.

Drugs used in chemotherapy are now known to be more than a 100 in number and can be
used alone or in combination therapies. Each drug has a different chemical structure and
composition. While surgery and radiation are invasive and targeted procedures, chemotherapy is
mainly systemic, traveling through the body to reach cancer cells.

Different types of chemotherapy drugs

Mode of action, chemical structure, composition, and homology to other drugs are factors that
help categorize chemotherapy drugs. Some drugs may fall into more than one category as they
may have multiple modes of action. To know the side effects of a particular drug, one must study
the mode of action. This information can later be incorporated by oncologists to predict how
effective a drug will work. In combination with chemotherapies, drug studies help decide the time,
order, and dosages of each drug administered in the therapy [39].

1. Alkylating agents

Direct DNA damage by alkylating agents stops the division of cancer cells and is
efficacious in all stages of the cell cycle. Many cancers are treated with alkylating agents such
as lymphoma, leukemia, multiple myeloma, Hodgkin’s disease, and sarcomas [40]. Also
included are several cancers of the ovary, breast, and lungs. On the downside of alkylating
agents, they can cause damage to bone marrow as they damage DNA. Long-term damage can
result in acute leukemia, depending on dosages used, although rarely. Leukemia from alkylating

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
agents arises after 5 to 10 years of treatment. Families of alkylating agents are given in table
0.2.

Class Names of drugs

Alkylating agents • Nitrogen mustards: such as mechlorethamine (nitrogen mustard),
chlorambucil, cyclophosphamide (Cytoxan®), ifosfamide, and
melphalan
• Nitrosoureas: which include streptozocin, carmustine (BCNU), and
lomustine
• Alkyl sulfonates: busulfan
• Triazines: dacarbazine (DTIC) and temozolomide (Temodar®)
• Ethylenimines: thiotepa and altretamine (hexamethylmelamine)

Antimetabolites • 5-Fluorouracil (5-FU)

• 6-Mercaptopurine (6-MP)
• Capecitabine (Xeloda®)
• Cladribine
• Clofarabine
• Cytarabine (Ara-C®)
• Floxuridine
• Fludarabine
• Gemcitabine (Gemzar®)
• Hydroxyurea
• Methotrexate
• Pemetrexed (Alimta®)
• Pentostatin
• Thioguanine

Anthracyclines • Daunorubicin
• Doxorubicin (Adriamycin®)
• Epirubicin
• Idarubicin

Mitotic inhibitors • Taxanes: paclitaxel (Taxol®) and docetaxel (Taxotere®)

• Epothilones: ixabepilone (Ixempra®)
• Vinca alkaloids: vinblastine (Velban®), vincristine (Oncovin®), and
vinorelbine (Navelbine®)
• Estramustine (Emcyt®)

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
Hormone • Prednisone, methylprednisolone (Solu-Medrol®), and
chemotherapeutic drugs dexamethasone (Decadron®)

Table 0.2 Various classes of anticancer chemotherapeutic drugs and their examples.

Based on similar mode of action of alkylating agents and platinum drugs, i.e., cisplatin,
carboplatin, and oxaliplatin, they are sometimes grouped together. These drugs have a reduced
tendency to cause posttreatment leukemia.

2. Antimetabolites

These drugs are analogs for the units of DNA and RNA, and hence by incorporation,
they stop growth of DNA and RNA. Such drugs particularly effect the S phase of the cell and
used for the treatment of leukemia, cancers of ovary, breast, intestinal tract, and various others.
Examples of antimetabolites are given in table 0.2.

3. Anthracyclines

These are antibiotics in nature that target DNA replication enzymes, affecting cells in
all phases of the cell cycle. Various cancers lie in the scope of these drug treatments. A big
limitation of these drugs is that exceeding a critical limit can permanently damage the heart.
Therefore, dose limits for a lifetime are determined for these drugs. Classes of anthracyclines
are mentioned in table 0.2.

4. Other antitumor antibiotics:

There are some antitumor antibiotics that do not belong to anthracyclines, including
actinomycin D+, bleomycin, and mitomycin C. Another anti-cancerous antibiotic is
mitoxantrone, comparable in many ways to doxorubicin, both of which can damage the heart at
a high dosage. Their mode of action is also the same, i.e., inhibiting the topoisomerase II, and
thus can lead to posttreatment acute myelogenous leukemia, after 2–3 years in most cases.
Prostate and breast cancers, lymphoma, and leukemia are also treated with mitoxantrone.

5. Topoisomerase inhibitors

Topoisomerase inhibitors deter the unwinding of DNA and hence stop DNA replication.
Some have leukemia; ovarian, gastrointestinal, and lung cancers; and others are treated with
these drugs. Examples of topoisomerase I inhibitors are topotecan and irinotecan (CPT-11), and
examples of topoisomerase II inhibitors are etoposide (VP-16) and teniposide. Mitoxantrone
also constrains topoisomerase II.

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
6. Mitotic inhibitors

Mitotic inhibitors are plant alkaloids and other naturally derived products in nature.
They inhibit the synthesis of proteins necessary for cell division, particularly in the mitotic
phase of the cell cycle, subsequently damaging all other phases too. Cancers treated with these
drugs include lung, breast, myelomas, leukemia, and lymphoma. Side effects such as peripheral
nerve damage can put limits on the dosages of these drugs. Examples of mitotic inhibitors are
given in table 0.2.

7. Miscellaneous chemotherapy drugs

Some uncategorized chemo drugs with uncommon modes of action include the enzyme
L-asparaginase and an inhibitor of proteasome called bortezomib (Velcade®). Examples
include drugs like L-asparaginase; it is an enzyme, and the proteasome inhibitor is bortezomib
(Velcade®).

❖ Hormone therapy

Advancements in the field of molecular biology in recent years clarified the role of hormones
in cell growth and in the regulation of malignant cells. Nearly 25% of tumors in men and 40% in
women are known to have a hormonal basis. Hormonal treatment is effective to treat cancer
without any cytotoxicity which is associated with chemotherapy. Steroids are hormones in nature,
and such hormone-like drugs are used in the treatment of cancers like lymphoma, leukemia, and
multiple myeloma. Moreover, corticosteroids are used as antiemetics, which give relief from
nausea and vomiting after chemotherapy. Also used before chemotherapy, they mitigate
hypersensitivity to the treatment. Only when used in actual chemotherapy procedures, these drugs
are called chemotherapeutic drugs. Examples of such drugs are given in table 0.3.

1. Anti-angiogenesis inhibitors

Nutrition to the tumor cells is provided by blood vessels, and the development of these
vessels inside tumor tissues is called angiogenesis. Some chemical inhibitors known as
“angiogenesis inhibitors” can cut off the blood supply to the tumor cells. These angiogenic
inhibitors like thalidomide, interferon, bevacizumab (Avastin), cilengitide (EMD 121974), and
cediranib (Recentin) VB-111 are sometimes administered in combination with the
chemotherapeutic drugs in an attempt to increase therapeutic efficiency of both (table 0.3).

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
Table 0.3: Different drugs involved in the treatment of cancer through different mechanisms.

Class Mechanism
Selective estrogen receptor modulators Block-binding site for estrogen; can slow the growth
(SARM) (tamoxifen and raloxifene) of estrogen stimulated cancers
Selective androgen receptor modulators Block-binding site for testosterone; can slow the
(SARM) growth of testosterone modulated cancers
Spindle inhibitors Stops cell replication early in mitosis
Farnesyl transferase inhibitors Blocks addition of farnesyl group to RAS, preventing
its action
Gleevec® Binds to abnormal proteins in cancer cells, blocking
their action
Angiogenesis inhibitors (endostatin, Prevent angiogenesis by tumor cells
angiostatin)
Immunostimulants (interleukin 2, alpha Enhance the normal immune response
interferon)
Herceptin Antibody that binds to HER2 receptor on tumor cell
preventing the binding of growth factors

❖ Role of stem cells in cancer treatment

Stem cells are undifferentiated cells present in the bone marrow with the ability to
differentiate into any type of body cell. A stem cell therapeutic strategy is also one of the
treatment options for cancer that are considered to be safe and effective. The application of
stem cells is yet in an experimental clinical trial; for example, their use in the regeneration of
damaged tissue like the heart, liver, bones, skin, cornea, etc. is being explored. Mesenchymal
stem cells are currently being used in trials that are delivered from the bone marrow, fat tissues,
and connective tissues.

D. Immunotherapy
Immunotherapy is a type of cancer treatment that helps your immune system fight cancer.
The immune system helps your body fight infections and other diseases. It is made up of white
blood cells and organs and tissues of the lymph system. Immunotherapy is a type of biological
therapy. Biological therapy is a type of treatment that uses substances made from living organisms
to treat cancer.
Several types of immunotherapy are used to treat cancer. These include:

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
• Immune checkpoint inhibitors are drugs that block immune checkpoints. These
checkpoints are a normal part of the immune system and keep immune responses from
being too strong. By blocking them, these drugs allow immune cells to respond more
• T-cell transfer therapy is a treatment that boosts the natural ability of your T cells to fight
cancer. In this treatment, immune cells are taken from your tumor. Those that are most
active against your cancer are selected or changed in the lab to better attack your cancer
cells, grown in large batches, and put back into your body through a needle in a vein. T-
cell transfer therapy may also be called adoptive cell therapy, adoptive immunotherapy, or
immune cell therapy.
• Monoclonal antibodies are immune system proteins created in the lab that is designed to
bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so
that they will be better seen and destroyed by the immune system. Such monoclonal
antibodies are a type of immunotherapy. Monoclonal antibodies may also be called
therapeutic antibodies.
• Treatment vaccines work against cancer by boosting your immune system’s response to
cancer cells. Treatment vaccines are different from the ones that help prevent disease.
• Immune system modulators enhance the body’s immune response against cancer. Some of
these agents affect specific parts of the immune system, whereas others affect the immune
system in a more general way.
Different forms of immunotherapy may be given in different ways. These include:
1. Intravenous (IV). The immunotherapy goes directly into a vein.
2. Oral. The immunotherapy comes in pills or capsules that you swallow.
3. Topical. The immunotherapy comes in a cream that you rub onto your skin. This type of
immunotherapy can be used for very early skin cancer.
4. Intravesical. The immunotherapy goes directly into the bladder.

Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
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Gerly Mark Redoble, MAN, CcPSW, RN, RN

 Republic of the Philippines
UNIVERSITY OF NORTHERN PHILIPPINES
Tamag, Vigan City
2700 Ilocos Sur
College of Nursing
Website: www.unp.edu.ph Mail: unpnursingvc@yahoo.com
CP# 09177148749, 09175785986
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