Treatments > Understanding Cancer Treatments

Last update: 01/30/2013

TOPICS:
 
Introduction | Specificity | Goals | Treatment Terms | Outcomes | Treatment Interventions | Types

See also Protocol Types & Treatment Terms | Questions

Here we provide background and terminology related to treatment goals, types, outcomes, and a summary of the various kinds of treatments so that you can better understand your doctor's recommendations and better participate in the decision process.

Symptoms, side effects, and selectivity 

Lymphoma cells are abnormal white cells (lymphocytes) that live too long or divide too fast. These malignant cells can accumulate to form tumors which can cause symptoms and impair the body's ability to function normally.  For example, lymphoma cells in the bone marrow may crowd normal cells and restrict the development of blood cells that originate in this organ, thus causing fatigue and susceptibility to infection - two common symptoms of lymphoma.

The general goal of treatment is to kill the cancer cells while minimizing damage to normal cells. When damage occurs to normal cells it produces side effects. For example, a chemotherapy drug may kill rapidly dividing cells. This will reduce symptoms of the disease if it kills lymphoma cells, but it will cause side effects if it also damages normal cells

"Most conventional chemotherapeutic agents are dose-limited by myelosuppression, 
and often have one or more other significant end organ toxicity [such as liver and kidneys] 
that may also prove dose limiting."  - Medscape

A drug is a chemical or compound that effects a disease process.  Drugs are administered in different ways and doses, and the administration of drugs is called a therapy,  regimen.  Also see for more detail:  What's a drug?

Treatments may be systemic - delivering drugs into the blood to reach cancer cells anywhere in the body, or localized - to treat a specific area of the body.  

Almost all therapies are selective to some degree. That is, they are designed to affect the targeted cells (cancer cells) more than the normal cells. For example, many chemotherapy drugs affect rapidly dividing cells and will therefore damage cancer cells and normal cells that divide rapidly.  Newer biotherapies, such as monoclonal antibodies, are selective in that they target only b-cells, but not other cell types, such as the stem cells from which mature b cells develop. Some investigative immune therapies target tumor cells exclusively.  In general, the greater the specificity of the treatment (how focused it is on killing just the tumor cells), the safer it will be.  

Examples of 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 dividing cells. 

See for details:

	elmhurst.edu - cancer drugs I and
	elmhurst.edu - cancer drugs II
	Clinical trials by type of agent

 

Examples of Therapy Specificity

Specific to:	Therapy type	Mechanism
Normal and  tumor cells	Targets dividing cells cytotoxic (chemotherapy)	DNA damage inducing apoptosis (cell suicide)
Class of cells: Mature B- lymphocytes	Targets CD20  Antibodies (Rituxan)	Cell signaling and/or causing an immune response  to cells bound by the antibody
Tumor specific	Targets molecular  defect in tumor (Btk, mTOR)	Mediating (causing) apoptosis  (cell suicide)
Tumor specific	Targets  antigen specific to tumor (Idiotype vaccines)	Indirect: mediating immune response
* The greater the specificity the less expected toxicity.  For investigational therapies the degree of specificity  is not always known until it is used in patients for many years. 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 risks 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.

The 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.

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Treatment goals:  Cure vs. Management

See also Treatment factors that influence timing and choice of therapy

Cure 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 - Medscape (free login req.)

Management - 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 treatments.

durable response - to select treatments or treatment combinations likely to obtain a durable, long-term disease-free response or remission.

overcome 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.)

watchful 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 Waiting.
 
1. (Horning S, Rosenberg S: The natural history of initially untreated low-grade non-Hodgkins lymphomas. N Engl J Med 311:1471-1475, 1984.)

Palliation - to treat minimally in order to relieve symptoms and improve quality of life.

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Treatment terms

Adjuvant therapy, also called adjuvant care, is treatment that is given in addition to the primary, main or initial treatment. Neoadjuvant therapy is the administration of therapeutic agents before a main treatment.

agents -  biotherapy | chemotherapy | immunotherapy (see Treatment Interventions for details.)

chemotherapy is the treatment of cancer with cytotoxic 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. 

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."  http://annonc.oxfordjournals.org

chemo-immunotherapy 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.  

consolidation 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.

EXAMPLES:

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 cells.
 

combination and sequential therapy - using a variety of treatment agents or types in combination or in sequence with the goal of cure, overcoming refractory disease, or producing 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. For example, using chemotherapy to reduce the tumor burden, followed by radioimmunotherapy might help to achieve better penetration and increase the cancer cell killing potential of the latter agent.  

front line, or first line - a treatment protocol used for patients that have previously had no prior treatment.

induction therapy - the primary protocol used to achieve the initial response, such as CVP-R, which might be followed by other therapy.

maintenance - additional chemo- or bio-therapy (anticancer drugs) sometimes used on a planned or fixed 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 of chemotherapy or Rituxan.  

Monoclonal 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

palliative - the goal is to achieve the best possible quality of life for patients, when the disease is not responsive to curative treatment.

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 remission. 

radio-immunotherapy (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 patients.  

salvage - 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 one treatment.

Surgery for lymphoma? The short answer and reason is no, 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 system. 

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.

stem 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 produced). These cells are replaced with the patient's own stem cells (harvested prior to treatment), or with matched donor cells. 

allogeneic 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 also purged of cancer cells before being returned to the patient.  

conditioning 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.

engraftment 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.

induction 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.

non-myeloablative 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 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 transplant.

myeloablative 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

complete 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. 

molecular remission (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. 

partial 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 disease.

progressing disease - 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.  

remission - most commonly means an inactive state of disease that results from a response to treatment. 

stable 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.

Also see How Drugs are Administered and What's a Drug? 

There are more than fifty chemotherapy drugs. Some are given as single agents, but often several drugs are combined into 'cocktails' or combination protocols. Also see Chemo Agents and Mechanisms 

Chemotherapy may be given orally or 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 body. 

Cells 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 

Chemo-immunotherapy - 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 effects. 
Also see Biologics and Rituxan

Also see: DETERMINANTS OF DRUG RESPONSE - Bing Search 
Basic principles on how chemotherapy works, mechanism of resistance, etc.

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.

growth 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

Immune therapies are treatments that induce the immune system to kill cancer cells.  

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 & Antibodies

Signals that induce self-killing, and/or   Immune Activation
 
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.

Radio-immunotherapy 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 for details.

Surgery 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.

Targeted 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 Emerging Treatment agents.  Treatments that target the blood supply to tumors are another example of a targeted treatments.  

Also see Targeted Therapies: Q&A - cancer.gov and 
2005 Meet the Expert: Targeted Therapies—The Next Generation - PLWC

"Targeted cancer 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 of life."

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