Chapter 88, Tobacco Use and Dependence.
Chemoprevention is the use of a drug or substance to reverse, inhibit, or prevent the
chemoprevention for these cancers, see Chapter 97, Breast Cancer, Chapter 99,
Colorectal Cancer, and Chapter 100, Prostate Cancer.
HUMAN PAPILLOMA VIRUS (HPV) VACCINES
QUESTION 1: M.M., a 44-year-old woman, asks you about vaccines to prevent cervical cancer. Should
The human papilloma virus is primarily transmitted through sexual contact;
serotypes 16 and 18 (HPV-16, -18) cause approximately 70% of cervical cancers.
There are three different HPV vaccines available, each requiring three intramuscular
injections over the course of 6 months. The HPV bivalent vaccine (Cervarix)
includes HPV types 16 and 18 whereas the HPV quadrivalent vaccine (Gardasil)
includes HPV types 6, 11, 16, and 18. Both vaccines demonstrated efficacy in
reducing the incidence of cervical intraepithelial neoplasia (CIN), a premalignant
lesion that can lead to cervical cancer.
15–17 Because the progression of HPV infection
to invasive cervical cancer requires several years to possibly decades, CIN is
utilized as a surrogate efficacy endpoint in HPV vaccine clinical trials. It is
anticipated that the use of HPV vaccines will ultimately lead to a reduction in the
The HPV 9-valent vaccine (Gardasil 9) includes the same HPV types as the
bivalent and quadrivalent vaccines (6, 11, 16, 18) but with five additional HPV types
(31, 33, 45, 52, 58), increasing prevention to approximately 90% of cervical
18 The HPV quadrivalent and 9-valent vaccines are also approved for the
prevention of vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial
neoplasia (VAIN) in females as well as prevention of HPV-related genital warts and
anal cancer in males. However, there are no data to support the use of these vaccines
to prevent other cancers associated with HPV, such as penile cancer or head and
Routine Pap smear and HPV screening should continue for vaccinated women
because the vaccines do not prevent all oncogenic types of HPV. The duration of
vaccine-induced anti-HPV immunity is also unknown.
M.M. should consider HPV vaccination for her daughter. All three vaccines are
indicated in females of 9 to 26 years of age, but the vaccines are most effective if
initiated before sexual activity. Whether or not M.M.’s daughter is vaccinated, she
should still receive routine Pap smear screening according to current guidelines.
The HPV quadrivalent and 9-valent vaccines are approved in males of 9 to 26 years
of age; therefore, M.M. should also consider vaccination for her son. The Centers for
Disease Control recommends HPV vaccination for all females and males at the age
Diet has been linked to the development of colon, prostate, and breast cancers. The
American Cancer Society advocates a healthy diet that consists of vegetables, fruit,
whole grains, and fiber and is low in fat and red meat.
21 For more information, visit
the following page on the American Cancer Society’s website:
http://www.cancer.org/Cancer/CancerCauses/DietandPhysicalActivity/index.
Migrant studies suggest that diet, environmental, or social factors play a role in the
development of prostate cancer and that the incidence of colon cancer in a population
increases as individuals migrate from a low-incidence region to a high-incidence
In women, the risk of breast cancer is increased with obesity and physical
inactivity, but an association with a high-fat diet is less clear.
consumption has also been associated with an increased risk of breast cancer.
more information, visit the following page on the American Cancer Society’s
website: http://www.cancer.org/Healthy/EatHealthyGetActive/index.
SUN AND ULTRAVIOLET RADIATION EXPOSURE
Most risk factors associated with skin cancer are uncontrollable, with the exception
of sun exposure and other forms of ultraviolet (UV) radiation. The interaction
between UV radiation and skin cancers is complex, because nonmelanomas (e.g.,
basal cell and squamous cell carcinomas) are associated with cumulative UV
radiation exposure and certain cutaneous melanomas are associated with excessive,
intermittent UV radiation exposure.
26 The risk of melanoma is further increased in
people who have a history of five or more severe sunburns in their lifetime,
particularly during adolescence, or history of tanning bed use.
ozone layer in the stratosphere may also contribute to the increased incidence of
Prevention of skin cancer is based on limiting sun and UV radiation exposure. The
American Cancer Society guidelines recommend avoiding or limiting sun exposure
from 10 AM to 4 PM when the UV rays are the strongest, and avoiding tanning bed or
sun lamp use. Protective clothing (hat, sunglasses, long-sleeved shirt, pants) and
sunscreens are also advised to minimize exposure.
27 However, the protective effects
of sunscreens alone against melanoma, particularly for intentional sun exposure, are
controversial and should not be used to prolong time in the sun.
Screening and Early Detection of Cancer
Standardized screening tests help identify disease in asymptomatic individuals
(screening) or diagnose disease in symptomatic individuals (early detection). The
cancer screening tests recommended by the American Cancer Society meet four basic
requirements: (a) There must be good evidence that the test is effective in reducing
morbidity or mortality; (b) benefits of the test should outweigh its risks; (c) costs of
the test should be in balance with its presumed benefits; and (d) the test should be
practical and feasible within the existing healthcare setting. For more information,
visit the following page on the American Cancer Society’s website:
Screening guidelines are updated frequently, and newest guidelines should be
consulted when counseling patients. Professional organizations including the
American Cancer Society (http://www.cancer.org) and National Comprehensive
Cancer Network (NCCN) (http://www.nccn.org) regularly publish
recommendations for screening of breast, cervical, colon, lung, and prostate
Diagnosis and Staging of Cancer
The histologic diagnosis of a tumor is the most important determinant of treatment
selection. This is because its histologic classification influences its natural history,
pattern of progression, and responsiveness to treatment. A biopsy followed by a
microscopic and biochemical evaluation by a pathologist can provide the most
accurate histologic diagnosis. Thereafter, staging can begin.
needed to select a treatment plan for J.S.?
The stage of the cancer, as well as the histologic diagnosis, influences both the
treatment selection and prognosis. Staging is the process that determines the extent or
Determining the stage of the cancer typically requires tests that can physically or
radiographically measure the size of the primary tumor and assess for evidence of
tumor spread (e.g., radiographs, computed tomography [CT] scans, magnetic
resonance imaging [MRI] scans, or positron emission tomography [PET] scans) and
pathologically examine regional lymph nodes.
30 Clinicians also evaluate symptoms
(e.g., pain) or signs (e.g., swelling, abnormal laboratory findings) that may indicate
tumor involvement at a distant site. Common sites of tumor metastases are shown in
Staging schemas have been developed for all major types of cancers. For solid
tumors, the most widely used and accepted staging classification is the TNM system,
which incorporates the size of the primary tumor (T), the extent of regional lymph
node spread (N), and the presence or absence of metastatic spread to distant organs
(M). Within each TNM category, the extent of cancer involvement is related to
prognosis. Most solid tumor staging systems also incorporate the TNM classification
into broader groups, called stages, to facilitate treatment decisions and comparison
among patient populations. Classification of stages differs among solid tumors types.
Please refer to malignancy-specific chapters for TNM staging of breast, lung,
prostate, and colorectal cancers.
Whereas the TNM system enables staging of solid tumors, it does not enable
staging for hematologic malignancies, including leukemias, lymphomas, and multiple
myeloma. Because hematologic malignancies occur in the blood cells and lymphatic
tissues that are widely distributed throughout the body, the TNM staging system
cannot sufficiently describe these diseases. To define the extent of disease, guide
treatment, and provide prognostic information, specific staging systems have been
developed for various hematologic malignancies. Staging systems for hematologic
malignancies are discussed in further detail in Chapter 96, Adult Hematologic
Common Sites of Metastases for Selected Tumors
Cancer Type Common Sites of Metastases
Breast Bone (osteolytic lesions), lung, liver, brain. ER-positive tumors preferentially spread
to bone; ER-negative tumors may metastasize to visceral organs
Lung Liver, brain, adrenals, pancreas, contralateral lung, and bone
Prostate Bone (osteoblastic lesions)
Colon The portal circulation pattern favors dissemination to the liver and peritoneal cavity,
but metastasis also occurs in the lungs
Ovarian Localspread in the peritoneal cavity
Myeloma Bone (osteolytic lesions), sometimes spreading to other organs
Staging systems for some tumors also include other characteristics to further
determine the stage and prognosis of the disease, such as clinical signs and
symptoms, biochemical characteristics of the tumor, or other laboratory tests. For
example, the staging system used for Hodgkin lymphoma includes constitutional
symptoms (i.e., fever, night sweats, and weight loss). These symptoms confer a
poorer prognosis and could indicate the need for more intensive therapy.
Tumor staging is done at the time of initial diagnosis and periodically during
treatment to assess the patient’s response to therapy. Staging should also be repeated
(a) when evidence shows that the cancer has progressed during treatment or recurred
after therapy to establish the most appropriate next-line therapy, and (b) to enable
measurement of response to that therapy.
J.S. needs to undergo the appropriate imaging scans, laboratory studies, and
clinical evaluation so that her breast cancer can be staged. These tests may include
blood tests (e.g., complete blood cell and platelet count, liver function tests),
mammograms or breast ultrasounds, determination of tumor ER/PR and HER2 status,
breast MRI, bone scan, abdominal scans, and chest imaging. Once staging is
completed, treatment recommendations and options can then be determined.
Treatment options for breast cancer based on stage are further discussed in Chapter
CLINICAL PRESENTATION AND COMPLICATIONS OF MALIGNANCY
The initial signs and symptoms of malignant disease are variable and predominantly
depend on histologic diagnosis, location (including metastases), and size of the
tumor. Pain secondary to compression, obstruction, and destruction of adjacent
tissues and organs is the most common presenting symptom. Other common initial
symptoms reported by patients with cancer include anorexia, weight loss, and fatigue.
Certain symptoms, however, may be obscured by a concomitant illness, such as
chronic lung disease in patients with lung cancer. Some tumors cause signs and
symptoms early in the course of the disease, whereas others may not cause symptoms
until late in the course of the disease and after significant tumor growth. In either of
early disease. Tumor involvement of the liver, kidneys, or lungs can complicate
therapy by causing significant organ dysfunction and metabolic disturbances. In
addition, compression or obstruction could produce a “mass effect” by impairing
normal organ or tissue function and causing pain or other uncomfortable physical
effects. Life-threatening complications that require immediate intervention include
obstruction of the superior vena cava, spinal cord compression, and brain metastases.
her abdomen shows a large mass surrounding the head of her pancreas with biopsy results that confirm
influence the type of treatment that she can receive?
Cancer can have a profound effect on a patient’s quality of life and his/her ability
to tolerate appropriate therapy. Patients with malnutrition secondary to anorexia,
mechanical obstruction, or pain may not tolerate some therapies because of
debility. Performance status is a measure of functional capacity and reflects a
patient’s ability to ambulate, care for himself/herself, and carry out normal activities.
For several cancers, poor pretreatment performance status is associated with
decreased ability to tolerate treatment, decreased tumor response to treatment, and
worsened clinical outcome. In these cases, especially if the cancer is not known to
respond well to treatment, a less aggressive treatment regimen may be recommended.
For this reason, performance status is important to assess at the time of staging
evaluation and periodically during treatment. Different scales (i.e., Karnofsky score,
Eastern Cooperative Oncology Group [ECOG]) can be used to determine
performance status. The Karnofsky and ECOG performance scales are depicted in
31 Because P.N. has a poor performance status (ECOG grade 3) and may
not tolerate chemotherapy well, her oncologist may recommend a less toxic treatment
plan. Because other conditions, such as depression, could contribute to her
symptoms, P.N. should undergo comprehensive evaluation.
treated? And what is the goal of therapy?
The choice of specific therapy and its goals depends not only on the histology and
stage of the cancer but also on the patient’s predicted tolerance of the side effects of
the various treatment options. The goal of therapy should always be to cure the
patient when possible. The likelihood of cure is greater when the tumor burden is
low (i.e., lower stage). When using therapy with curative intent is not possible,
therapy becomes palliative in nature, with disease control and symptom management
the priority. Goals of therapy should be balanced so that quantity and quality of life
are both adequately considered.
Cancer is predominately treated with three modalities: surgery, radiation, and
systemic therapy (including chemotherapy, targeted therapy, biologic response
modifiers, etc.). Systemic therapy is the primary treatment modality for hematologic
malignancies. In most solid tumor malignancies, early-stage and localized disease is
treated with either surgery or radiation therapy. Sometimes, combinations of
modalities may be used to maximize the potential for cure or disease control (e.g.,
radiation given in combination with chemotherapy). For advanced disease (presence
of metastases or recurrence after initial therapy), solid tumor malignancies are
usually treated with systemic therapy as the primary treatment modality. T.J.’s
treatment will be dependent on tumor histology, stage, and expected prognosis. If T.J.
has potentially curable disease, he should be treated with curative intent therapy,
whereas if T.J. has advanced disease that denotes a poor prognosis, he should be
treated with palliative therapy.
Surgery is an important treatment option for patients diagnosed with certain solid
tumors. With the recent advances in surgical techniques (e.g., minimally invasive
procedures) and improved understanding of patterns of tumor growth and spread,
successful resections are possible for an increasing number of patients. Surgery may
be used as preventive therapy (e.g., removal of colonic polyps or cervical dysplasia)
or diagnostic treatment, or staging of some cancers.
Eastern Cooperative Group (ECOG) Karnofsky
Grade Description Grade Description
0 Fully active, able to carry on all predisease
performance without restriction
100 Normal, no complaints; no evidence of
90 Able to carry on normal activity; minor signs
1 Restricted in physically strenuous activity but
ambulatory and able to carry out work of a
80 Normal activity with effort, some signs of
70 Cares for self but unable to carry on normal
2 Ambulatory and capable of allself-care but
unable to carry out any work activities. Up
and about more than 50% of waking hours
60 Requires occasional assistance but is able to
care for most of personal needs
50 Requires considerable assistance and frequent
3 Capable of only limited self-care, confined to
bed or chair more than 50% of waking hours
40 Disabled; requires special care and assistance
30 Severely disabled; hospitalization is indicated
4 Completely disabled. Cannot carry on any
self-care. Totally confined to bed or chair.
20 Very ill; hospitalization and active supportive
Surgery can be used to manage both localized and advanced tumors. When surgery
provides curative therapy for a localized tumor, the surgeon removes the tumor plus a
margin of normal tissue surrounding the tumor. For extensive, localized tumors that
cannot be completely removed, selected patients may undergo cytoreductive surgery
to resect the tumor partially in an attempt to improve the likelihood that subsequent
chemotherapy or radiation therapy may successfully kill the tumor.
Patients with metastatic disease may have palliative surgery to relieve pain or
improve functional abnormalities caused by the advanced tumor (e.g., gastrointestinal
obstruction). Palliative surgery may improve quality of life without prolonging
Radiation may be administered as either curative or palliative therapy for solid
tumors. Radiation is administered in varying doses depending on the type of tissue
(e.g., bone, lung, breast, liver, brain) being treated and the intent of therapy
(palliative or curative). A limit exists to the total amount of radiation that can be
delivered to the area being treated dependent on the type of tissue. Damaging effects
of radiation on the normal tissues that surround the tumor can be dramatic, and may
be exacerbated if given concomitantly with chemotherapy. Chemotherapy that
follows completion of radiation therapy can produce “radiation recall” of local
toxicity that manifests as skin redness, swelling, and peeling at the radiation site.
Not all cancers are sensitive to radiation, so this modality has limited application
in these cases. For radiation-sensitive tumors (Table 93-4), potential advantages
exist over surgery. For instance, radiation therapy may encompass a wider area
around the tumor and treat tumors in regions of the body where surgery cannot safely
be performed. Radiation therapy also can be used when surgery could result in
considerable disability or disfigurement. Patients may receive radiation therapy to
multiple sites simultaneously.
Multiple methods are used to administer radiation to tumors. External-beam
radiotherapy and brachytherapy are two types that are commonly used. Newer
radiation therapy techniques, including intraoperative radiation, hyperfractionated
treatment planning, may reduce associated toxicities, enhance tumor responsiveness,
and improve the clinical usefulness of radiation.
Cancers Frequently Treated with Radiation Therapy
Acute lymphocytic leukemia (central nervous system radiation)
Brain and central nervous system
Head and neck cancers, squamous cell
Not all cancers can be treated by surgery or radiation therapy. Patients may present
with widespread metastatic disease at diagnosis or recur following primary treatment
with surgery or radiation. Patients may also have residual tumor following initial
surgery or radiation, requiring additional treatment. In these circumstances, systemic
treatments including chemotherapy, targeted therapy, endocrine therapy, and biologic
response modifiers generally offer the only hope of controlling disease.
The National Cancer Institute defines chemotherapy as drugs that treat cancer cells.
For the purposes of this chapter, chemotherapy will be defined as cytotoxic therapy
that is directed toward rapidly dividing cells. Chemotherapy kills cancer cells by
damaging DNA, interfering with DNA synthesis, or inhibiting cell division.
Chemotherapy agents are classified by their effect on the cell cycle or mechanism of
of the cell cycle are referred to as phase-nonspecific agents or dose-dependent agents
(Fig. 93-1). The specific mechanisms of action for several chemotherapy agents are
Factors that Influence Response to Chemotherapy
Studies using rodent animal models during the 1960s demonstrated that the number of
tumor cells killed by chemotherapy is proportional to the dose when the growth
fraction is 100% (i.e., all cells are dividing) and the tumor cells are sensitive to the
36,37 For example, if a dose of chemotherapy reduces the tumor burden from 10
8 cells, the same dose administered when only 10
5 cells. This theory has become known as the cell-kill
or log-kill hypothesis (Fig. 93-2).
In the clinical setting, tumor cells do not always decrease predictably with each
successive course of chemotherapy. This is because the growth fraction of human
tumors is not 100% and the cell population is heterogeneous, with some cells that are
Dose intensity is defined as the chemotherapy dose per unit time during which
treatment is given (e.g., mg/m2
/week). Drug resistance might be overcome by
increasing the dose of chemotherapy. Evidence suggests that reducing a dose can
cause treatment failure in patients with chemotherapy-sensitive tumors who are
having their first chemotherapy treatment.
38 A direct relationship between dose
intensity and response rate also has been reported in several human tumors including
breast cancer, lymphomas, ovarian cancer, and small-cell lung cancer.
dose-intensive therapy has not consistently improved the overall cure rate of most
higher doses, patients may receive hematopoietic growth factors, autologous stem
cell transplantation, or altered schedules of drug delivery.
Chemotherapy is administered in cycles (e.g., every 2, 3, or 4 weeks) with recovery
periods between cycles. A typical course of chemotherapy usually consists of several
cycles. The interval of time between cycles depends on the type of cancer and the
Administration Notable Toxicities
Nitrogen mustards (and related
PO Also: rash; hepatic dysfunction;
pulmonary fibrosis; myoclonus,
IV, PO Also: immunosuppression;
hemorrhagic cystitis; alopecia;
Ifosfamide (Ifex) IV Also: hemorrhagic cystitis
Also: anaphylaxis, rash, blurred
function via crosslinking of DNA and
vomiting; peripheral neuropathy;
IV Also: electrolyte abnormalities
Cisplatin (Platinol) IV, IP Also: renal dysfunction;
IV Also:sensitivity to cold, jaw
leading to doublestrand breaks and
Busulfan Cross-links DNA IV, PO Myelosuppression; pulmonary
vomiting; neurologic toxicity;
hepatic dysfunction; secondary
DNA demethylation agents Incorporates into
IV or SC Also: injection-site reaction
IV Also: electrolyte abnormalities;
IV Also:somnolence, dizziness,
seizure, peripheral neuropathy;
Folic acid antagonists Inhibits
IV, PO Also: renal dysfunction;
IV Also: fever; edema; diarrhea;
IV Also: fever; fatigue; headache;
IV Also: headache; rash, pruritus;
hypotension; diarrhea; hepatic
IV Also: fever, chills; edema;
PO Also: rash; drug fever; hepatic
PO Also: hepatotoxicity, venoocclusive disease; stomatitis;
hyperuricemia; fluid retention
PO Myelosuppression; dermatologic
Pyrimidine analogs Incorporates into
vomiting, stomatitis, diarrhea
(fever, myalgia, bone pain, rash,
IV Also: flu-like syndrome; rash,
Epothilones Binds directly to βtubulin; promotes
arthralgia, myalgia; stomatitis,
Taxanes (and related agents) Binds to β-tubulin;
peripheral neuropathy; myalgia,
edema; hypersensitivity reaction
Paclitaxel (Taxol) IV, IP Also: hypersensitivity reaction
Vinca alkaloids Binds to tubulin
Myelosuppression; constipation;
IV Also: autonomic neuropathies
IV Also: fatigue; liver dysfunction
Halichondrin B analog Disrupts
nausea, constipation; peripheral
single- and doublestrand DNA breaks
IV Also: diarrhea; fatigue, rigors,
Doxorubicin IV Also: acute cardiac toxicity;
IV Also: fatigue; stomatitis; rash,
Intravesical Urinary urgency; urinary
producing singleand double- strand
IV Erythema, hyperpigmentation;
pulmonary toxicity; fever, chills
vomiting; hepatic dysfunction;
Cephalotaxine Inhibits ribosome
reaction, injection-site reaction;
hyperuricemia; infection, fever,
Differentiation Agents Promotes myeloid
dermatologic toxicity; headache,
myelosuppression, leukocytosis;
leukocytosis; cardiac effects;
psychiatric; lipid abnormalities
DNA Topoisomerase Inhibitors Inhibits
IV, PO Also: nausea, vomiting;
IV Also: diarrhea, cholinergic
IV, PO Also: nausea, vomiting, diarrhea
of inappropriate antidiuretic hormone.
The optimal schedule is also influenced by the pharmacokinetics of the agent. For
example, phase-specific agents exert their cytotoxic effects only when the cell is in a
particular phase of the cell cycle. If a phase-specific agent with a short half-life is
administered by intravenous bolus, a significant number of tumor cells will not be in
the vulnerable phase of the cell cycle during exposure to the agent. Comparatively,
the same agent administered by frequent intravenous bolus or continuous infusion
could expose more cells to the agent during the vulnerable phase.
QUESTION 1: B.C. is a 39-year-old male with aggressive non-Hodgkin lymphoma (NHL). At the time of
and how should his treatment be altered?
11 cells. Two trillion (2 × 10
) cells or 2 kg of tumor is lethal to humans. An effective chemotherapy
occur during the recovery period until further chemotherapy is given at point C.
Most likely, B.C.’s cancer is now growing because the tumor has become resistant
to the chemotherapy. Therefore, it would be wise to discontinue the current regimen.
Biochemical resistance to chemotherapy is the major impediment to successful
38 Resistance can occur de novo in cancer cells or
develop during cell division as a result of mutation.
mathematical model known as the Goldie–Coldman hypothesis predicted that tumor
cells mutate at a rate related to the genetic instability of the tumor.
probability that a tumor mass will contain resistant clones is related to both the rate
of mutation and the size of the tumor. Many mechanisms have been identified by
which cancer cells resist the activity of cytotoxic agents.
Some cell lines that become resistant to a single chemotherapy agent may also be
resistant to structurally unrelated cytotoxic compounds. This phenomenon is called
pleiotropic drug resistance or multidrug resistance (MDR).
this type of resistance are generally resistant to natural product cytotoxic agents such
as the vinca alkaloids, antitumor antibiotics, epipodophyllotoxins, camptothecins,
and taxanes. The primary mechanism believed to be responsible for MDR is an
increase in efflux transporters such as P-glycoprotein in the cell membrane. These
proteins mediate efflux of the chemotherapy agent, causing decreased accumulation of
drug within the cell and decreased cytotoxicity.
45 Other transport proteins (e.g.,
breast cancer resistance protein) have been implicated in resistance to chemotherapy
Another type of MDR is resistance caused by changes or mutations of drug targets,
for example, the altered binding of topoisomerase II, an enzyme that promotes DNA
strand breaks in the presence of anthracyclines and epipodophyllotoxins.
of the likelihood of MDR, B.C. should receive a chemotherapy regimen that does not
include agents transported from tumor cells by the MDR mechanism. An alternative
regimen such as gemcitabine or oxaliplatin, with or without rituximab, may be a
reasonable option because this regimen is active against NHLand these drugs are not
known substrates for various efflux transporters.
The cytotoxic effects of chemotherapy agents are related to the time the tumor is
exposed to an effective concentration of the agent (i.e., concentration × time [C × T]).
The drug dose, infusion rate, route of administration, lipophilicity, and protein
binding can influence the concentration–time product. Other factors, such as tumor
size and location, can also critically affect an agent’s cytotoxicity. As tumors grow
larger, their degree of vascularity lessens, making it more difficult for agents to
penetrate the entire tumor mass. Tumors located in sites of the body with poor drug
penetration (e.g., the brain) may not receive a sufficient concentration to provide
Antitumor activity and adverse effects of chemotherapy agents are associated with
the presence of genetic polymorphisms that can affect the metabolism and disposition
of drug. See Chapter 97, Breast Cancer, and Chapter 99, Colorectal Cancer, for a
more detailed discussion of genetic polymorphisms associated with UGT1A1,
CY2D6, and HER2/neu receptor positivity.
QUESTION 1: K.K. has newly diagnosed stage II, bulky Hodgkin lymphoma. She initially presented with
Although single-agent chemotherapy can cause significant early regression of
Hodgkin lymphoma, acute lymphocytic leukemia, and adult NHL, some tumors show
only a partial, very short response to single-agent therapy. In Hodgkin lymphoma, the
use of combination chemotherapy results in long-term, disease-free survival for more
than 60% of patients. If K.K. were to receive single-agent therapy, her disease would
not be cured. Combination chemotherapy is recommended to provide her with the
best chance for long-term, disease-free survival.
Combination chemotherapy provides broader coverage against resistant cell lines
within the heterogeneous tumor mass. Several principles provide the basis for
selecting the agents to be included in a chemotherapy regimen:
Agents with demonstrable single-agent activity against the specific type of tumor
should be used in combination therapy.
Agents in the regimen should have different mechanisms of action.
Agents should not have overlapping toxicities so that the severity and duration of
acute and chronic toxicities are minimized.
Agents in the regimen should be used in their optimal dose and schedule.
Subsequent chapters will provide examples of commonly used systemic regimens
in the treatment of hematologic and solid tumor malignancies.
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