| Treatment Terms |
also Protocol Types &
Our goal is to help you to better understand your doctor's
treatment recommendations so you can take part in the decision
Informed participation starts with a
basic understanding of the disease.
Lymphoma cells arise from lymphocytes. These are white
blood cells that have acquired defects causing the cells to persist
too long and or to divide too rapidly - causing the cells
to accumulate and form tumors.
As a tumor grows it can impair the body's ability to function normally
leading to symptoms. For example,
tumors in the bone marrow can crowd normal cells and restrict the development of blood cells that
arise in this organ, leading to fatigue and susceptibility to infection
common symptoms of advanced lymphoma.
The best cancer treatments
kill the abnormal cells while minimizing damage to normal cells.
Scientists call this the therapeutic specificity.
Effective treatments can reduce tumor burden or eliminate the cells
completely, providing relief from the disease symptoms.
However, the activity of a treatment can also damage normal cells
leading to side effects.
Doctors sometimes refer to these competing effects or tradeoffs as
the risk/benefit ratio ... which can be very different for
each treatment plan.
Risk, Benefit Assessments
The overall risk/benefit
assessment is based on many factors, such as
The potential efficacy of the
treatment, including the duration of the response
The common and less common possible side
Serious or not, long lasting or
The out-of-pocket costs (financial toxicity?)
Your quality of life while on
treatment (especially if the treatment schedule is long)
So, for a given treatment protocol
the potential for benefit can be common or uncommon.
The benefit can be long or short-term.
the risks (possible side effects) can also common,
uncommon, rare ...
reversible or permanent, serious or easily managed
Here are important points about side effects:
Adapted from the NCI Informed Consent
The doctors may not know who will
or will not have side effects.
Some side effects may go away
soon, some may last a long time, or some may never go away.
Some side effects may interfere
with your ability to have children.
Some side effects may be serious
and may even result in death.
Here are important points about how you
and the study doctor can make side effects less of a problem:
Tell your doctor if you notice or
feel anything different so they can see if you are having a side
Your doctor may be able to treat
some side effects.
Your doctor may adjust the study
drugs to try to reduce side effects.
Your preferences can play a part in the decision
When there is no widely agreed upon best treatment
protocol, the following aspects of the treatment can help you and
your doctor to make a choice that is the best fit for you:
The dose and schedule, and
how the drug is given (by mouth or by vein)
The duration of the treatment
The anticipated impact for
good or bad on your quality of life
The types of risks, and how
serious they may be
The potential for a cure or durable
The treatment that's least
unlikely to interfere with your life goals or work in the
short or long term
The treatment that does not impact your
sexual function or fertility
Basic terms - drugs and protocols
is a chemical or compound that inhibits a disease process or relieves
the symptoms of a disease.
Also see for
more detail: What's a drug?
You can find information about a particular drug by
using the NCI Drug Dictionary -
Drugs are given (administered) in different ways and doses.
How drugs are given and the dose of the drug is called a therapy,
protocol, or regimen.
The optimal dose and schedule of a cancer drugs are arrived at in
clinical trials in phase I, dose-finding safety studies. The
optimal dose and schedule of an effective drug will lead to tumor
shrinkage with acceptable types and severity of side effects.
This is sometimes referred to as the therapeutic index or therapeutic window.
See also Therapeutic index -
Types of Protocols based on how they are given or
Adjuvant therapy, also called adjuvant care
treatment given in
addition to the primary, main or initial treatment.
the administration of therapeutic
agents before a main treatment.
drugs taken by mouth, and at home. May or may not be
influenced by foods. Patient adherence can be an
issue. Out of pocket costs can be higher than drugs given by
Intravenous (IV) route
drugs given by vein at the cancer center. Requires
travel. Typically given less frequently than oral drugs
although some IV drugs are given continuously for long periods
of time with a portal pump.
The treatments may be
where the drug enters the blood to reach cancer cells anywhere in the
body, or localized - to treat a
specific area of the body.
Combination or concurrent therapy
using a variety of treatment
agents or types in combination concurrently (at the same time) often
with the intent to cure,
overcome refractory disease, or achieve a durable response.
(Also see maintenance and consolidation within. ) The concept is
that some agents may be more effective when given prior to, or just
after, another agent.
treatment given soon after the induction therapy, often with the intent
overcome refractory disease, or achieve a durable response.
(Similar to maintenance, but usually of shorter duration.)
Front line, or
first line therapy
a treatment protocol used for patients that have previously had no
the primary protocol used to
achieve the initial response, such as Bendamusting-R, which might be followed
by other therapy. Also called backbone therapy.
Maintenance or management therapy
additional therapy following induction therapy used on a schedule over longer
periods of time. The purpose can vary, but typically maintenance
therapy, such as with Rituxan, has been used to maintain or sustain
a response to treatment with chemotherapy or Rituxan.
using a variety of treatment
agents in sequence often with the intent
overcome refractory disease, or achieve a durable response.
Therapy with intent to cure or achieve
treatment given with intent to cure or
induce a remission that endures many years. Typically
favored and recommended for aggressive disease that can be
rapidly fatal if not cured, or for high-risk or variable-risk
Therapy with intent to manage as needed
treatment given with intent to manage the disease as needed,
generally using protocols with lower toxicity than protocols
given with curative intent. May be considered as initial
therapy for indolent lymphoma that have lower risk and less
anticipated need for treatment over time, or in the relapse
treatment given with intent to relieve symptoms and
to improve quality of life, but not expected to prolong life.
=== Under construction.
Mechanisms of Action for Cancer Drugs
Mechanism means how a therapy works, or is thought to
induce cancer cells to die or stop dividing. Some therapies work
in multiple ways. Indeed, the mechanisms by which different
chemotherapy agents work can vary in how they effect the DNA of
Examples of Therapy
Targets dividing cells
DNA damage inducing apoptosis (cell suicide)
Class of cells:
Cell signaling and/or causing an immune response
to cells bound by the antibody
defect in tumor
Mediating (causing) apoptosis (cell suicide)
Targets antigen specific
Indirect: mediating immune response
* The greater the specificity the less expected
For investigational therapies the degree of specificity
is not always known until it is used in patients for many
There can be unexpected short or long term toxicity.
When selecting a treatment, you and
your doctor will consider the potential short- and long-term
and benefits of the various treatments in relation to
the risks associated with your particular diagnosis.
For example, if
the type of lymphoma you have is slow growing
it may be appropriate to monitor it and treat only when
necessary. How a treatment might limit the use of a subsequent treatment
("burning bridges") could also be of importance for some types of lymphoma.
For example, repeat or high dose use of purine analogs, such as
Fludarabine, may make it difficult to harvest stem cells in future, or
prevent you from benefiting optimally from some immune therapies.
good news is that lymphomas are often very sensitive and responsive to
treatments. Aggressive lymphoma are often cured, and indolent
lymphomas are often easy to manage. Importantly, recent advances in
the understanding of lymphoma has led to effective new therapies and
better therapies are certain to follow.
or durable remission - to give therapies (typically aggressive therapies such as
combination chemotherapy) with the goal of killing all the
malignant cells. Significant short-term side effects are
accepted because the benefit of cure or remission duration outweighs the risks of the
treatment. Cure is
often the goal of treatment for aggressive (fast growing) lymphomas,
and indolent lymphomas that are diagnosed while possibly localized
to one or two areas of the body. We are hopeful that sequences of
new therapies will make this goal a reality for more types of
lymphomas and other cancers.
Aggressive NHL: "When you
move to aggressive lymphomas, you are curing about 45%, as you saw
on the prior slide. At relapse, if you transplant the chemosensitive
eligible patients, you can get about a 53% cure rate, but that
represents only 10% of the original patient population, and that is
superior to the results achieved with salvage chemotherapy." Current Therapies in the Treatment of Non-Hodgkin's Lymphoma: Chemotherapy - Richard I. Fisher, MD
(free login req.)
- to treat minimally only when the disease causes symptoms. The goal
is to reduce symptoms, and reduce the amount of disease burden
with minimal toxicity; or keep the disease at bay. This approach is
also called palliative
response - to select treatments or treatment
combinations likely to obtain a durable, long-term disease-free
response or remission.
refractory disease - to select treatments, perhaps
investigational treatments, that will produce a response
(regression of lymphoma) in patients who have disease that has not
responded to standard treatments. (See Salvage below.)
waiting (w&w) - refers to deferring treatment while
the patient pursues a normal life and daily activities.
W&W is often appropriate, particularly for some kinds of
indolent lymphomas when the patient is not experiencing symptoms.
The rationale for w&w is that standard treatments cannot yet
cure indolent lymphoma, and these treatments can cause side effect
that are not justified in patients who are not yet experiencing
symptoms. Furthermore, early use of standard treatment have not
yet shown the ability to improve overall survival. 1
Also see Rationale for Watchful
1. (Horning S, Rosenberg S: The natural history of initially
untreated low-grade non-Hodgkins lymphomas. N Engl J Med
- to treat minimally in order to relieve symptoms and improve
quality of life.
biologic therapy |
chemotherapy | immunotherapy (see
Interventions for details.)
Almost all therapies have some degree
of specificity. That is, they are designed to affect the cancer cells more than normal cells.
Virtually every treatment that has a potential to benefit you will
also have possible side effects.
the treatment of cancer with cytotoxic drugs that can damage
the DNA of dividing cancer cells. This damage can cause the
cells to self-destruct in a process called apoptosis:
cytotoxic drugs: Many agents of this type trigger apoptosis by damaging DNA - particularly in dividing
cells. This mechanism is similar to how too much sun can trigger exposed skin cells to peel.
Apoptosis: programmed cell death - a normal process by which
the body rids itself of old, unneeded, or damaged cells. This mechanism is similar to how too much sun can trigger exposed skin cells to peel.
Notable quote: "Lumping all
of these treatments under the term ‘chemotherapy’, or even
‘multi-agent chemotherapy’, does the profession and the public a
disservice, by not recognizing the profound differences in mechanism
of action, therapeutic index and treatment outcome from these
different types of treatment."
"Most conventional chemotherapeutic agents are dose-limited by myelosuppression,
and often have one or more other significant end organ toxicity [such as liver
that may also prove dose limiting." - Medscape
is the treatment of cancer with drugs that can destroy cancer cells in
combination with agents (such a Rituxan) that direct the immune system to
identify and kill the cells.
therapy is that which is given shortly after
the induction therapy, with the goal of
improving the quality of the response - getting rid of minimal
residual disease that might exist at a sub-clinical level - not
detectable with image tests and does not cause symptoms.
Consolidation therapy (or sequential therapy) is sometimes
considered when there is a high likelihood of relapse , such as for a
high-risk type lymphoma - one that tends to relapse often,
particularly if its behavior is aggressive and challenging to treat
effectively if it relapses.
Radioimmunotherapy has been used as consolidation therapy following
chemotherapy ... the FIT study for example tested chemo followed by
Zevalin, which won marketing approval based on the result compared
to chemo alone.
Vaccine is an investigational consolidation therapy ... so far, the
results were not good in two comparative studies and encouraging but
inconclusive in a third (2011).
Rituxan maintenance is a kind of consolidation therapy ... but here
the rationale is to delay relapse with a therapy that has relatively
low toxicity (compared to getting extra chemo)
NOTE: Chemo consolidation -- maintenance with chemo for
as long as 2 years -- is
a major reason for the high cure rate in childhood cancers!
High dose chemotherapy is a kind of consolidation that requires stem
cell support because of the negative impact of the treatment on stem
cells - either from your cells harvested earlier or from donor stem
antibodies (Mabs) man-made antibody that may induce killing of b-cells - malignant
and normal - by inducing self killing, or by flagging the cells for attack
by the immune system. See Rituxan
- the goal is to
achieve the best possible quality of life for patients, when the disease is not responsive to curative
primary treatment - this term
is sometimes used to describe the first therapy that uses significant
doses or combinations of agents with the goal of obtaining a
(RIT) agents are man-made
antibodies with different radiation components attached. These
antibodies are designed to bind to a protein shape called CD20,
which sticks out of mature B lymphocytes (immune cells), both
malignant and nonmalignant (cancerous and normal). ...
... Importantly, the cd20 shape (or antigen / receptor) is not found on precursor B cells
- immature b-cells which can later mature to replenish the supply of
normal mature b-cells.
RIT is considered a targeted therapy, because the antibodies that
deliver the radiation are specific to one type of cell. RIT is more potent
than unlabeled antibody therapy, such as Rituxan, but it also has more
potential risk. Importantly, there is clinical data
suggesting that RIT is very potent and can induce
complete responses that are very durable (measured in years), even in
heavily pre treated
- a term often applied to combinations of chemotherapy drugs
used to treat lymphomas, after relapse in which the patient is either not
responsive (refractory) to standard protocols, or the patient has general health
consideration (allergies, lung, or heart problems) that require the use of
unusual combinations of treatment agents, dosing, or dosing schedules. Be
aware that despite the negative connotation of "salvage," these
novel treatment regimens can sometimes achieve remissions.
second-line - a treatment protocol used for patients that have previously had
lymphoma? The short answer and reason is
because lymphoma is considered a systemic condition; that is,
the cells are expected to be widely distributed, AND, it is also
sensitive to systemic therapies - that are infused into the blood
More detail: Lymphoma is a cancer affecting lymphocytes, a
type of blood cell that fight infection, thus these cells can
migrate anywhere in the body. Lymphoma cells behave like normal lymphocytes in this regard and therefore are not treated by surgery,
even if only detected by imaging in one or two spots.
(NOTE: Lymphocytes are tiny and mobile by design. It takes a lot of abnormal lymphocytes to accumulate before they can be imaged (seen) by CT or even PET ... there are about 2 billion cells in a 1 cm lymph node)
The good news is that abnormal blood cells (like normal blood cells) are typically highly sensitive to many treatments (quick to self-destruct)... Thankfully, cures are common for many kinds of leukemias and lymphomas from both radiation and chemo therapies. Other blood cancers are very treatable even if rarely cured.
That our blood counts drop quickly with treatment, but many other cell types in our body are completely unaffected - also illustrates
the basic difference between blood and so-called "solid" cancers. Widespread
(systemic) lymphomas can be completely reversed, but widespread (metastasized)
breast or prostate cancer would be devastating.
cell transplant (bone marrow transplant) - the goal of
this type of treatment is to cure the patient with aggressive therapies
that partially or completely kills off (ablates) the normal stem
cells in the marrow (the spongy tissue found in the cavities of the body's bones, where all the body's blood cells are
These cells are replaced with the patient's own stem cells
(harvested prior to treatment), or with matched donor cells.
bone marrow transplant (allo) - .Any bone marrow transplant
between two individuals, whether they are related or unrelated. The stem
cells the patient
receives can come from the bone marrow through a surgical procedure or from the peripheral
blood (peripheral blood stem cell transplant, PBSCT).
autologous bone marrow transplant
(auto)- stem cells from the patient's own
marrow are removed, stored and then returned to the body after the patient receives high
doses of chemotherapy and/or radiotherapy therapy. Sometimes, the portion of marrow is
of cancer cells before being returned to the patient.
phase - high-dose therapy that wipes out or
"conditions" the immune system and bone marrow in
preparation for the stem cells harvested previously. This phase might include
Total Body Irradiation (TBI), and more recently, high dose bexxar
- an investigational alternative to TBI.
phase - the stem cells are given back to the patient to
reconstitute the immune system. Sometimes purging techniques are
used to clean the stem cells of residual tumor cells prior to
engraftment, or shortly after.
therapy typically consists of conventional doses of
chemotherapy administered in an attempt to reduce the amount of
cancer in a patient’s body, prior to high-dose therapy in
preparation for a stem cell transplant.
transplant - less aggressive therapy designed to reduce
tumor burden but not kill off (ablate) the myeloid cells in the
bone marrow, but to reduce their number enough to allow for
successful grafting of donor cells. See mini-transplant below.
mini transplant is often called a non-ablative or non-myeloablative
transplant, and sometimes adoptive
immunotherapy -- Non-myeloablative,
because the pretreatment does not ablate (kill off) the bone marrow -
Adoptive immunotherapy, because the adopted donor immune cells act against the
disease when the transplant is given.
mobilization therapy - use of
growth factors or other treatments which leads to the proliferation and mobilization of stem cells from a dormant microenvironment of the bone marrow to an environment that promotes their expansion, differentiation and mobilization to the bloodstream.
These cells are then harvested in order to replace stem cells
damaged from aggressive treatments in preparation for a stem cell
therapy - aggressive therapy designed to completely
kill off (ablate) the myeloid cells in the bone marrow, in
preparation for donor cells in a stem cell transplant.
Vaccine therapy - The
goal of vaccine therapy is to teach the immune system to recognize and
attack tumor cells. Vaccines may improve the duration of response to
standard treatments without adding significant toxicity, or precluding
the use of other treatments.
See for details
response (CR) - describes a response to treatment
when no lesions are detected
by CT imaging and other tests, and normalization of
biochemical abnormalities (such as LDH) that associated with the lymphoma. If CT imaging and a bone marrow test show no evidence
of disease, it is a more rigorously defined complete response.
Sometimes in general practice (not in a clinical trial) a CR is
declared based on CT imaging results alone, even when no bone marrow
test is performed.
(MR) - a type of remission based on the clearance of
bcl-2-positive cells from the blood and/or bone marrow, as determined by
sensitive PCR tests. This test measures the possible degree of a
complete response because it indicates that lymphomas cells (which
over express this protein) have been significantly reduced or
cleared from the body. The significance of an MR is still not
totally clear, but having a molecular remission might predict the
duration of response in patients with bcl-2 positive tumors.
response (PR) - describes a response to therapy in which least a 50% reduction in
measurable tumor burden is measured. As the name suggests, some
residual disease is observed in a partial response. You may be
considered in remission after a partial response if your
disease is not active at this point
you no longer experience the symptoms that
prompted the need for treatment - that is, you have stable
- patient is experiencing symptoms (fever, night sweats, etc.) and when lymph nodes
increase in size or new enlarged lymph nodes or tumors outside the
lymphatic system (extranodal
lesions) are observed.
- most commonly means an inactive state of disease that
results from a response to treatment.
disease - a patient is considered to have stable or regressing disease when they
do not experience symptoms and when lymph nodes or extranodal lesions are not growing, or
are observed to be regressing in size. Sometimes this condition
or clinically observed inactivity of the disease is
described as a remission.
Treatment Interventions - basic types
How Drugs are
What's a Drug?
is the treatment of cancer with drugs that can destroy cancer cells.
Cancer cells often divide and form cells without control. Chemotherapy
agents are often used in combinations with the goal of killing cells
that are actively growing. Normal cells can also be harmed by
chemotherapy agents, especially normal cells that divide quickly, such as
hair and immune cells. These undesired actions cause side effects. Also
see Side Effects.
There are more
than fifty chemotherapy drugs. Some are given as single agents, but
often several drugs are combined into 'cocktails' or combination
Agents and Mechanisms
Chemotherapy may be given
by IV (a line placed into the arm or a port). It's a systemic
therapy - the drugs are
infused into the blood so they can reach cancer cells all over the
that take up the drugs are damaged and this damage imitates a program
in the cell called apoptosis - programmed cell death. Think of
sunburn as an example of apoptosis: The strong sun exposure damages
skin cells, and this damage causes the cells to commit suicide. We
experience this as peeling skin.
Continuous Low-dose (metronomic)
chemo: There has also been a growing interest in low-dose oral chemotherapy as a
means of reducing toxicity and improving responses. This type of regimen
might be called salvage as well, but we prefer the word
"novel." Also see Chemo - oral low dose
- biologic agents in combination
with chemotherapy: Rituxan, a
monoclonal antibody often used to treat lymphomas that express CD20,
is also used in combination with chemotherapy to enhance its
Also see: DETERMINANTS OF DRUG RESPONSE -
Also see Biologics and Rituxan
Basic principles on how chemotherapy works, mechanism of resistance,
You might think of biotherapies as compounds more closely related
to naturally produced compounds created within the body. The FDA
defines a biotherapy as any therapeutic serum, protein, vaccine,
virus, blood, blood component or derivative product,
or derivatives applicable to treatment. Also see Biologics
Biotherapies can be systemic
or localized treatments.
The compounds are
generally infused into the blood or injected into the skin so they can
reach cancer cells or interact with normal cells to produce direct or
indirect therapeutic effects.
factors - proteins in products such as Neupogen, that
when injected stimulate the body to produce blood cells. These are
often given with standard treatments to help your body recover
from therapy and reduce the chance of infection associated with
low blood counts. Also see Biologics
monoclonal antibody therapies
(mAb) - proteins (antibodies) of a shape that when infused seek
and bind to receptors on cells that express a complementary
shape. Rituxan is an monoclonal antibody therapy that binds
to b cells that have cd20 expressed. Also see Rituxan
are treatments that induce the immune system to kill cancer
The goal of cancer vaccines is to induce active
immunity against unique proteins specific to the tumor
cells. Here the immune system "learns" about the identity
of the tumor and "remembers" this information in order to
produce a sustainable attack and long-term surveillance. Also see Vaccines.
Antibody therapy also induces immune activation against
cells that are engaged by the antibody, but this is called passive
immunity because once the antibody leaves your system,
the immune activation will not be maintained. Also see Rituxan
Signals that induce self-killing, and/or
Here are two illustrated ways that antibodies may kill tumors.
(Click images to enlarge.) In the illustration, NK represents
Natural Killer cells, but other effector cells can engage the
antibody to induce killing, such as macrophages.
Biotherapies may also be considered targeted
therapy. See below.
uses high-energy x-rays to kill tumors in a wide area or field, or
localized to treat a specific tumor. Since radiotherapy
affects the areas radiated, it can be effective as a management
intervention -- when there is a need to shrink a problem lymph node,
for example. Radiotherapy is sometimes combined or sequenced with
chemotherapy. Also see Radiotherapy.
use monoclonal antibodies (mAbs) to deliver
radio-isotopes to kill tumors in
a more targeted way, and induce immune activation against the targeted
cells as well. Also see Radioimmunotherapy
is used to remove by resection (cut out) malignant cells. Most
often this is not used to treat lymphoma, which is generally a systemic
(wide spread) disease. However, at times, and for some kinds of lymphoma,
surgery is indicated and can be effective. Also see Splenectomy.
therapies are designed to disrupt or interact with
mechanisms of cell biology that are specific to the cancer cells and
not normal cells. They are more likely to be biological than
chemical compounds. Velcade is a recent therapy. Also see
Treatment agents. Treatments that target the blood supply to
tumors are another example of a targeted treatments.
Therapies: Q&A - cancer.gov and
2005 Meet the Expert: Targeted Therapies—The Next Generation - PLWC
therapies will give doctors a better way to tailor cancer treatment.
Eventually, treatments may be individualized based on the unique set
of molecular targets produced by the patient’s tumor. Targeted
cancer therapies also hold the promise of being more selective, thus
harming fewer normal cells, reducing side
effects, and improving the quality
Gene Therapy (Investigational)
"is a technique for correcting defective genes responsible for
disease development. Researchers may use one of several approaches for
correcting faulty genes." See for details: ornl.gov
Common Treatment Types
Chlorambucil, Cytoxan, ... numerous
used to manage lymphoma
aggressive therapy - most often used with Rituxan for
aggressive therapy - most often used with Rituxan for
may be effective in refractory disease
potent targeted single agent therapy
numerous second generation Mabs are in the pipeline
aggressive therapy - most often used with Rituxan for
Prednisone, Decadron®, Methylprednisolone
Fast acting; often used with chemotherapy and
Rituxan, Bexxar, Zevalin, Campath
, Zolinza, various.
Many investigational agents. See Pipeline
FavId, Myvax, Biovax
The goal of vaccine therapy is to teach the immune system
to recognize and attack tumor cells.