VELEZ COLLEGE
DEPARTMENT OF OCCUPATIONAL THERAPY
F.RAMOS ST. CEBU CITY
Principles of Cancer
Treatment
SUBMITTED BY:
CHIONGBIAN, APRIL GRACE A.
BSOT-IV
SUBMITTED TO:
DR. GERRARD DENNIS UY, MD
The goal of cancer treatment: eradicate the cancer.
If this primarygoal cannot be accomplished, the goal of cancer treatment shifts to palliation, the
amelioration of symptoms, and preservation of quality of life while striving to extend life.
When cure of cancer is possible, cancer treatments may be undertaken despite the certainty ofsevere
and perhaps life-threatening toxicities. Every cancer treatment has the potential to cause harm, and
treatment may be given that producestoxicity with no benefit. The therapeutic index of many
interventionsis quite narrow, and most treatments are given to the point of toxicity.
When the goal is palliation, careful attention to minimizing the toxicity of potentially toxic treatments
becomesa significant goal. Irrespective of the clinical scenario, the guidingprinciple of cancer treatment
should be primum succerrere,, “first hasten to help.” Radical surgical procedures, large-field
hyperfractionated radiation therapy, high-dose chemotherapy, and maximum tolerable doses of cytokines
such as interleukin (IL) 2 are all used in certain settingswhere 100% of the patients will experience toxicity
and side effectsfrom the intervention and only a fraction of the patients willexperience benefit. One of the
challenges of cancer treatment is to use the various treatment modalities alone and together in a fashion
that maximizes the chances for patient benefits
Cancer treatments divided into four main types:
Surgery
Radiation therapy
Chemotherapy
Biologic therapy
modalities are often used in combination, and agents in one category can act by several mechanisms.
Oncology, the study of tumors including treatment approaches, is a multidisciplinary effortwith surgical-,
radiotherapy-, and internal medicine–related areasof expertise. Treatments for patients with hematologic
malignanciesare often shared by hematologists and medical oncologists.
Cancer mimics an organ attempting to regulate an own growth. Cancers have no limit on how much
growth should be permitted. Normal organs and cancers share the same properties:
Population of cells in cycle and actively renewing
Population of cells not in cycle
cancer stem cells,
Properties are being elucidated. The stem cell fraction may define new targets for therapies that
will retard their ability to reenter the cell cycle.
PRINCIPLES OF CANCER THERAPY
Prophylaxis
Cancer can be prevented by surgery in people who have premalignantlesions resected
Those who are at increased risk of cancer from either an underlyingdisease
Presence of genetic lesions or a developmental anomaly
Prophylactic surgery is more radical than surgeries used to treat after the cancer develops
The assessment of risk involves many factors andshould be undertaken with care before advising
a patient to undergosuch a major procedure.
Diagnosis
Obtain as much tissue safety as possible
light-microscopic inspection of a tumor for pattern of growth, degree of cellular atypia,
invasiveness, and morphologic features that aid in the differential diagnosis
Histologically similar tumors may have very different gene expression patterns when assessed by
such techniques as microarray analysis using gene chips
goals are best met by an excisional biopsy in which the entire tumor mass is removed with a
small margin of normal tissue surrounding it
If an excisional biopsy cannot be performed, incisional biopsy is the procedure of second choice.
A wedge of tissue is removed, and an effort is made to include the majority of the cross-sectional
diameter of the tumor in the biopsy to minimize sampling error.
Core-needle biopsy usually obtains considerably less tissue, but this procedure often provides
enough information to plan a definitive surgical procedure.
Fine-needle aspiration generally obtains only a suspension of cells from within a mass.
Staging
important component of patient management is defining the extent of disease.
Radiographic and other imaging tests can be helpful in defining the clinical stage;
Pathologic staging requires defining the extent of involvement by documenting the histologic
presence of tumor in tissue biopsies obtained through a surgical procedure.
Treatment
Surgery is the most effective means of treating cancer
removal of tumor can obtain important benefits, including local control of tumor, preservation of
organ function, debulking that permits subsequent therapy to work better, and staging information
on extent of involvement.
laparoscopic approaches are being used to address primary abdominal and pelvic tumors. Lymph
node spread may be assessed using the sentinel node approach, in which the first draining lymph
node a spreading Tumor would encounter is defined by injecting a dye into the tumor site at
operation and then resecting the first node to turn blue
chemotherapy and/or radiation therapy is delivered to reduce the size of the tumor and clinically
control undetected metastatic disease. Such therapy is followed by a surgical procedure to
remove residual masses; this is called neoadjuvant therapy
Palliation
Surgery is employed in a number of ways for supportive care
Surgical bypass of gastrointestinal, urinary tract, or biliary tree obstruction can alleviate symptoms
and prolong survival.
Rehabilitation
Assure proper ambulation
PRINCIPLES OF RADIATION THERAPY
Physical properties and biologic effects
Radiation is a physical form of treatment that damages any tissue in its path;
selectivity for cancer cells may be due to defects in a cancer cell’s ability to repair sublethal DNA
and their damage.
Therapeutic radiation is delivered in three ways:
(1) teletherapy, with beams of radiation generated at a distance and aimed at the tumor within the patient;
(2) brachytherapy, with encapsulated sources of radiation implanted directly into or adjacent to tumor
tissues;
(3) systemic therapy, with radionuclides targeted in some fashion to a site of tumor.
- X-rays and gamma rays are the forms of radiation most commonly used to treat cancer.
- orbital electron ejection is called ionization.
- waves behave biologically as packets of energy, called photons
tissues that the beam passes through to get to the tumor are called the transit volume
Radiation is quantitated on the basis of the amount of radiation absorbed in the patient
APPLICATION TO PATIENTS
Teletherapy
Radiation therapy can be used alone or together with chemotherapy to produce cure of localized
tumors and control of the primary site of disease in tumors that have disseminated
Individualized treatment planning employs lead shielding tailored to shape the field and limit the
radiation exposure of normaltissue.
Brachytherapy
placing a sealed source of radiation into or adjacent to the tumor and withdrawing the radiation
source after a period of time precisely calculated to deliver a chosen dose of radiation to the
tumor.
Radionuclides and Radioimmunotherapy
Nuclear medicine physicians or radiation oncologists may administer radionuclides with
therapeutic effects. Iodine 131 is used to treat thyroid cancer since iodine is naturally taken up
preferentially by the thyroid
Monoclonal antibodies and other ligands can be attached to radioisotopes by conjugation
Photodynamic Therapy
Some chemical structures (porphyrins, phthalocyanines) are selectively taken up by cancer cells
by mechanisms not fully defined. When light, usually delivered by a laser, is shone on cells
containing these compounds, free radicals are generated and the cells die. Hematoporphyrins
and light are being used with increasing frequency
TOXICITY
Though radiation therapy is most often administered to a local region, systemic effects, including
fatigue, anorexia, nausea, and vomiting, may develop that are related in part to the volume of
tissue irradiated, dose fractionation, radiation fields, and individual susceptibility. Bone is among
the most radioresistant organs, radiation effects being manifested mainly in children through
premature fusion of the epiphyseal growth plate.
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Chronic toxicities are more serious. Radiation of the head and neck region often produces thyroid
failure. Cataracts and retinal damage can lead to blindness. Salivary glands stop making saliva,
which leads to dental caries and poor dentition.
PRINCIPLES OF CHEMOTHERAPY
Medical oncology
subspecialty of internal medicine that cares for and designs treatment approaches to patients with
cancer, in conjunction with surgical and radiation oncologists.
END POINTS OF DRUG ACTION
Chemotherapy agents may be used for the treatment of active, clinically apparent cancer
eradicate a local tumor or as part of multimodality approaches to offer primary treatment to a
clinically localized tumor.
Chemotherapy is routinely used in “conventional” dose regimens
potentially life-threatening complications that require intensive support, usually in the form of
hematopoietic stem cell support from the patient (autologous) or from donors matched for
histocompatibility loci (allogeneic)
CANCER DRUGS: OVERVIEW AND PRINCIPLES FOR USE
4 broad types:
conventional therapy agent
targeted agents
hormonal therapies
biologic therapies
2 valuable outcomes of therapies mentioned:
induce cancer cell death
induce cancer cell differentiation
cell death:
necrosis
o cell death induced, for example, by physical damage with the hallmarks of cell swelling
and membrane disruption
apoptosis
o highly ordered process whereby cells respond to defined stimuli by dying, and it
recapitulates the necessary cell death observed during the ontogeny of the organism.
Anoikis
o refers to the death of epithelial cells after removal from the normal milieu of substrate,
particularly from cell-to-cell contact.
Chemotherapeutic agents used in cancer treatment
Direct DNA-interactive agents
Synthesis or s-phase of the cycle
divided into “phase-nonspecific” agents, which can act in any phase of the cell cycle, and “phasespecific” agents, which require the cell to be at a particular cell cycle phase to cause greatest
effect.
Formation of Covalent DNA adducts
Alkylating agents as a class are cell cycle phasenonspecific agents.
Broken” or cross-linked DNA is intrinsically unable to complete normal replication or cell division;
further activates cell-signaling pathways that can precipitate apoptosis
Cyclophosphamide is inactive unless metabolized by the liver to 4-hydroxy-cyclophosphamide,
which decomposes into an alkylating species, as well as to chloroacetaldehyde and acrolein.
Ifosfamide is a cyclophosphamide analogue also activated in the liver,
Nitrogen mustard (mechlorethamine) is the prototypic agent of this class, decomposing rapidly in
aqueous solution to potentially yield a bifunctional carbonium ion
Chlorambucil causes predictable myelosuppresion, azoospermia, nausea and pulmonary side
effects.
Busulfan causes profound myelosuppression, alopecia and pulmonary toxicity but is relatively
lymphocyte sparing
Procarbazine is metabolized in the liver and possibly in tumor cells to yield a variety of free
radical and alkylating specieas
Cisplatin requires administration with adequate hydration, including forced diuresis with mannitol
to prevent kidney damage
Hypomagnesemia attends cisplatin use and can lead to hypocalcemian and tetany
Carboplatin displays less nephro- , oto-, and neurotoxicity.
Oxaliplatin is a platinum analog with noteworthy activity in colon cancers refractory to other
treatments.
ANTITUMOR ANTIBIOTICS AND TOPOISOMERASE POISONS
Antitumor antibiotics
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Substances produced by bacteria that appear to provide a chemical defense against other hostile
microorganisms.
Topoisomerase poisons
Natural products or semisynthetic species derived ultimately from plants and modify enzymes that
regulate the capacity of DNA to unwind to allow normal replication or transcription.
Topoisomerase I
o Creates sing-strand breaks that then rejoins following the passage of other DNA strand
Topoisomerase II
o Double strand breaks through which another segment of DNA duplex passes before
rjoining
Doxorubicin
Intercalate into DNA altering DNA structure, replication and topoisomerase II function.
Undergo reduction reaction
Causes predictable yelosuppresion, alopecia, nausea and mucositis.
Bleomycin
Mixture of glycopeptides that have the unique feature of forming complexes with iron whil also
bound to DNA
Cleared rapidly but augmented skin and pulmonary toxicity in the presence of renal failure
Vesicant and can be administered intravenously, intramuscularly of subcutaneously
Mitomycin C
Undergoes reduction of its quinone function to generate a bifunctional DNA alkulataing agent
Active anti-neoplastic agent with a number of unpredictable toxicities including:
o Delayed bronchospasm 12-24h after dose and chronic fibrosis syndrome more frequent
at doses 50-60mg/ m2
Mitoxantrone
Synthetic compound that was designed to recapitualt features of doxorubicin but with less
cardiotoxicity.
Cases of actue promyelocytic leukima
Etoposide
Synthetically derived from the plant product podophyllotoxin.
Binds directly to topoisomerase II and DNA in a reversibleternary complex
Alkali-labile DNA bond
Camptothecin
Extracts of a Chinese tree and had notable antileukemia activity
INDIRECT EFFECTORS OF DNA FUNCTION: Antimetabolites
Antimetabolites
Compounds with structural similarity to precursors of purines or pyrimidines, or compounds that
interfere with purine or pyrimidine synthesis.
Cause DNA damage indirectly abnormal timing or progression through DNA synthesis, or altered
function of pyrimidine and purine biosynthetic enzymes.
Methotrexate
Inhibits dihydrofolate reductase
Cleared by the kidney bia both glomerular filtration and tubular section
Bone marrow suppression and mucosal irritation and renal failure at high doses owing to
crystallization in renal tubules
Low-dose cause hepatic fibrosis
Pemetrexed
novel folate-directed antimetabolite
multitargeted inhibiting the activity of several enzymes.
Received along with low-dose folate and vitamin B12 supplementation.
Cytosine arabinoside
Incorporated into DNA after formation of ara-CTP, resulting S-phase-related toxicity
Adverse effects include nausea, diarrhea, stomatitis, chemical conjunctivitis and cerebellar ataxia.
Fludarabine phosphate
Prorug of F-adnine arabinoside
Designed to diminish the susceptibility of ara-A to adenoside deaminase
Causes inhibition of ribonucleotide reductase and susceptibility to apoptosis
Renal failure and CNS dysfunctions are notable toxicities
Asparaginase
Bacterial enzyme that causes breakdown of extra-cellular aspargine required for protein synthesis
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Effectively stops tumor cell DNA synthesis
Hypersensitivity reactions are common
Mitotic Spindle Inhibitors
Vincristine is metabolized by the liver, and dose adjustment in the presence of hepatic
dysfunction is require.
o Neuropathic effects: jaw pain, paralytic ileus, urinary retention, and the syndrome of
inappropriate antidiuretic hormone secretion
Vinorelbine is a vinca alkaloid that appears to have differences in resistance patterns in
comparison to vincristine and vinblastine; it may be administered orally. taxanes stabilize
microtubules against depolymerization. “stabilized” microtubules function abnormally and are not
able to undergo the normal dynamic changes of microtubule structure and function necessary for
cell cycle completion
Taxanes include:
o Paclitaxel
o docetaxel
Estramustine was originally synthesized as a mustard derivative that might be useful in
neoplasms that possessed estrogen receptors.
Hormonal Agents
Glucocorticoids are generally given in “pulsed” high doses in leukemias and lymphomas, where
they induce apoptosis in tumor cells.
o Cushing’s syndrome or inadvertent adrenal suppression
o Pneumocystis pneumonia
Tamoxifen is a partial estrogen receptor antagonist; it has a tenfold greater antitumor activity in
breast cancer patients whose tumors express estrogen receptors than in those who have low or
no levels of expression
Aromatase refers to a family of enzymes that catalyze the formation of estrogen in various
issues, including the ovary and peripheral adipose tissue and some tumor cells.
Diethylstilbestrol (DES) acting as an estrogen at the level of the hypothalamus to downregulate
hypothalamic luteinizing hormone (LH) production results in decreased elaboration of
testosterone by the testicle.
Total Androgen Blockade
o Combined use orchiectomy or leuprolide plus flutamide
Targeted therapies
Hematopoietic Neoplasms
o Imatinib
 Targets the ATP binding site of protein tyrosine kinase that is formed as the
result of the chromosome 9,22 translocation producing the Philadelphia
chromosome in CML
o Nilotinib
 Tyrosine protein kinase inhibitor with a similar spectrum of activity to imatinib, but
with increased potency and perhaps better tolerance by certain patients.
o All-trans-retinoic acid
 Targets the OML retinoic acid receptor alpha fusion protein
 Adverse effects:
 Headaches with or without pseudotumor cerebri
 Gastrointestinal cutaneous toxicities
o Bortezomib
 Inhibitor of the proteasome, the multi-subunit assembly of protease activities
responsible for the selective degradation of proteins important in regulating
activation of transcription factores.
o Vorniostat
 Inhibitor of histone deactylases, responsible for maintaining the proper
orientation of histones on DNA, with resulting capacity for transcription factors
and therefore increased expression of genes that are selectively repressed in
tumors.
o DNA methyltransferase inhibitors
 Increase transcription of genes silenced during the pathogenesis of a tumor by
causing demethylation of the methylated cytosines that are acquired as an
epigenetic modification of DNA
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Solid tumors
o Small-molecule epidermal growth factor antagonists
 Act at the ATP binding site of the EGF receptor tyrosine kinase.

o
o
Gefitinib showed evidence of responses in a small fractions of patients with nonsmall cell lunch cancer.
Multitargeted kinase antagonists
 Small-molecule ATP site-directed antagonists that inhibit more than one protein
kinase.
Hand-foot syndrome
 Erythema and desquamtation of the distal extremities
Acute Complications of Cancer Chemotherapy
Myelosuppresion
o Common cytotoxic chemotherapeutic agents almost invariably affect bone marrow
function
o Complications result from the predictable sequelae of the missing cells’ function
o Febrile neutropenia
 Clinical presentation of fever in a neutropenic patient with an uncontrolled
neoplasm involving the bone marrow or, more usually, in a patient undergoing
treatment with cytotoxic agents.
 Management: empirical coverage with antibiotics for the duration of neutropenia
o Primary prophylaxis
 G-CSF to patients receiving cytotoxic regiments is associated with 20%
incidence of febrile neutropenia

Nausea and vomiting
o Most common side effect of chemotherapy administration
o Acute: within 24 hours
o Delayed: >24 hours
o Antineoplastic agents vary in their capacity to cause nausea and vomiting
o Emesis – reflex caused by stimulation of the vomiting center in the medulla
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Diarrhea
o Regimens that include fluorouracil infusions and/or irinotecan
o Immediate or delayed (48-72 hours)
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Mucositis
o Irritation nd inflammation of the mucous membranes particularly afflicting the oral and
anal mucosa
o Due to damage to the proliferating cells at the base of the mucosal squamous epithelia or
in the intestinal crypts.
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Alopecia
o Antimetabloites more variably associated with alopecia
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Gonadal dysfunction and pregnancy
o Cessation of ovulation and azospermia reliably result from alkylating agents
o Female – experience amenorrhea with anovulation after alkylating agent therapy
BIOLOGIC EFFECTS
Immune mediators of antitumor effects
Tumors have variety of means of avoiding immune system:
1. Often only subtly different from their normal counterparts
2. They are capable of downregulating their major histocompatibility complex angtigens
3. Inefficient at presenting antigens to the immune system
4. Cloak themselves in a protective shell of fibrin to minimize contact with surveillance mechanisms
5. Produce a range of solumbe molecules including potential immune targets
Cell Mediated Immunity
1. Allogeneic T cells are transferred to cancer-bearing hosts in 3 major settings
a. Allogeneic bone marrow transplantation
b. Pure lymphocyte transfusions following bone marrow recovery
c. Pure lymphocyte transfusions following immunosuppressive therapy
2. Autologous T cells are removed from the tumor-bearing host, manipulated in several ways in vitro
and given back to the patient. 2 major classes
a. To develop tumor antigen-specific T cells and expand them to large numbers over many
weeks ex vivo before administration
b. To activate the cells with polyclonal stimulaters
3. Tumor vaccines are aimed at boosting T cell immunity.
Antibodies
Not very effective at killing cancer cells
Easier for the tumors to fend off.
Antibodies to CD52 are active in chronic lymphoid leukemia and T cell malignancies
EGF-R directed antibodies have activity in colorectal cancer
Anti-VEGF antibody bevacizumab shows little evidence of anti-tumor effect when used alone, but
with chemotherapeutic agents, it improves the magnitude of tumor shrinkage and time to deases
progression
Side effects:
o Infusion-related hypersensitivity reactions
o Acneiform rash
Cytokines
Greater than 70 separate proteins and glycoproteins with biologic effects in humans.
Interferon alpha beta and gamma
o Not curative for any tumor but can induce partial responses in follicular lymphoma, hairy
cell leukemia, CML melanoma, and Kaposi’s sarcoma
IL – 1 through 29
o IL-2 exer its antitumor effects indirectly through augmentation of immune function
o IL-2 associated with myriad clinical side effects:
 Intra vascular volume depletion
 Capillary leak syndrome
 Adult respiratory distress syndrome
 Hypotension
 Fever
 Chills
 Skin rash
 Impaired renal and liver function
GENE THERAPY
No gene therapy has been approved for routine clinical use
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