Cancer Guides

The doctor-patient relationship has changed. In times past, patients dutifully followed doctors' orders with few questions. Today, more patients are making medical decisions in partnership with their health decisions in partnership with their health care teams. It's not easy, due in part to the ever-increasing number of treatment options available.

For some patients, the right choice is treatment with a goal of cure, as long as there is some chance that outcome is possible, and regardless of the risks and costs of treatment. For others, cure is not the best goal because the chance of achieving that outcome is low and the price (discomfort, travel, expense, risk of death or complications) is high.

Doctors can provide patients with statistical data for each treatment option regarding chances of remission, cure rates, complications, side effects and mortality. They might be able to give some idea of what the treatment experience will be like. Survivors who have been through similar treatments can usually offer insight into what to expect, and doctors can refer patients who are willing to share their recollections and advice.

As patients weigh their options and discuss them with their doctors, they should consider these steps:

 Patients shouldn't try to decide which choice is best at the time they receive their diagnosis—just identify as many options as possible, even if some seem far-fetched. Research indicates that most patients want complete medical information from doctors and to share the decision-making authority with them by creating a true partnership. Different doctors could recommend different drug or treatment combinations at various intervals. Then again, the best treatment might be no treatment. Patients diagnosed with certain slow-growing cancers may be given the option of being closely monitored (“watchful waiting”) if there are no serious symptoms.

 Once patients have a list of options, they should weigh the positives and negatives about each one. The goal is to know the risk versus the benefit of each option.

 Patients should find out as much as they can about each option by talking with their doctors and doing research. For a crash course in any cancer, as well as news of cutting-edge treatments, visit cancer.org, cancer.net or cancer.gov

 Patients should make sure the resources they check are credible.

 A medical decision can mean different things to different people. Patients should understand how medical decisions can affect their quality of life and how these choices may affect their loved ones.

 It can be a tremendous relief for both patient and doctor once they settle on a treatment plan, but in the world of cancer, each decision carries a measure of uncertainty. Patients soon come to understand what oncologists have always known: Their treatments might or might not be effective. But in all cases, it is important that patients follow through with their plans, knowing that they are making the wisest choices they can at that time.

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Taking the right steps can help patients handle the stress of treatment selection.

Making Medical Decisions

Every patient has the option to get a second opinion about any aspect of diagnosis or treatment. In fact, getting a second opinion is common, and several situations could actually call for one.

Whether there is concern about a recommended treatment or just a desire to hear the diagnosis confirmed from another physician, a second opinion is appropriate. A patient might also seek a second opinion if the pathologist is having difficulty making a diagnosis, if he or she has a rare type of cancer that their doctor is unfamiliar with, if the patient thinks the doctor underestimates the seriousness of the disease or if their medical insurance plan requires one.

Patients can request a second review of their pathology slides or another opinion about treatment if their choices are numerous and they want reassurance they have chosen wisely. A second opinion can clarify a diagnosis or provide treatment options about which a patient was not aware, including those offered through clinical trials.

Patients should seek a second opinion from a physician outside their current doctor’s practice. They shouldn’t worry about offending their doctor; most oncologists expect patients to seek a second opinion. Some suggest it and offer recommendations.

Many local hospitals, regional cancer centers and institutions, including the National Cancer Institute (cancer.gov) and the National Comprehensive Cancer Network (nccn.org), have physician referral services that provide consultations for second opinions. Some large cancer centers have formal second-opinion programs designed to provide advice quickly. They do this by scheduling patients to see doctors of different specialties all in one day. In addition, some cancer centers offer second opinions from afar, based on records and images that are sent to them. This allows patients to seek second opinions from top experts without traveling.

Seeking a second opinion from an expert in the patient’s specific cancer can provide another viewpoint. Such an expert could suggest clinical trials the patient’s doctor might be unaware of or confirm a treatment recommendation.

People in support groups and other cancer survivors can also be good sources for recommending oncologists and specialists.

Patients can also identify experts through scientific journal articles about their cancer types. Doctors who have authored several articles on a particular cancer are generally considered experts and might be available for a second opinion and consultations. Patients should inquire about online or telephone referrals, especially if they want a second opinion from an expert at a large cancer center or one who practices far from where they live. Be aware, however, that consultations can be expensive and might not be covered by insurance.

Before seeking a second opinion‚ patients should obtain information about their disease, including diagnosis, staging, treatment options and how recurrence might be prevented. They should ask their physician to send test results and imaging scans to the consulting doctor. Patients might need to repeat some tests, but the second doctor will want to look over existing test results and scans.

Some insurance plans cover, or even require, second opinions before approving payment for treatment. Some plans limit coverage to certain physicians or hospitals, so it is always best for patients to consider their plans when coordinating second-opinion appointments.

Some patients might get confused about what advice to follow if the second doctor recommends a different treatment, which might be likely if their cancer does not have a set standard of therapy.

For example‚ both surgery and radiation therapy might be suggested as options for a patient with early prostate cancer, because both treatments have excellent long-term cure rates. A urologist who specializes in prostate surgery might be more inclined to recommend surgery than a radiation oncologist would. In that case, the decision would depend on how the patient weighs the side effects of each treatment in relation to his own personal views and lifestyle. A patient’s primary care physician could also have helpful advice about weighing inconsistent recommendations.

Patients might also want to seek a third opinion if they are still uncomfortable with their diagnosis or treatment options. Although it might not be necessary for their cancer to be treated by a specialist, they might want to hear the opinion of someone who focuses only on their type of cancer, especially if their first two doctors recommended different therapies or had conflicting diagnosis results.

After weighing the options, patients must decide on their medical teams. Most patients proceed with their initial doctors, but comfort level, proposed treatment options and medical expertise should all be evaluated when making a decision.

Why and how patients should get another opinion about their diagnosis and treatment.

Seeking a Second Opinion

Scientists continue to learn more about cancer’s biology and how it affects each patient. As they make new discoveries, they are able to refine existing treatments and develop new ones. In addition, research continues to lead to new combinations of different types of drugs that fight cancer more effectively together, such as pairings of chemotherapy with radiation or groupings of chemotherapy with immunotherapy and a targeted drug.

In many cases, surgery can be used to remove a tumor and, depending on the pathology of the cancer, the surrounding tissue. In some circumstances, patients might be eligible for less invasive surgical options.

 requires one or more small incisions that allow a thin fiber-optic scope, called a laparoscope, and specially designed surgical instruments to be inserted into the body to remove the tumor. Disease-free survival and recurrence rates for specific tumor types and stages seem to be about the same with laparoscopic surgery compared with traditional open surgery. The main benefits are faster recovery times, shorter hospital stays and fewer complications. A similar technique, used for lung and other thoracic cancers, is thoracoscopic surgery, during which a tiny camera and surgical instruments are inserted through a thin incision in the chest wall.

 could have even more benefits for some patients. As with laparoscopic surgery, robot-assisted procedures require a few small incisions. But instead of directly manipulating the surgical instruments, the surgeon sits at a console to perform the procedure by directing robotic arms. The process enables finer movements yet prevents the surgeon from feeling the tissue in the same way as in open surgery. In addition to prostatectomy (surgery to remove the prostate gland), robot-assisted surgery can be used for hysterectomy to treat cervical and endometrial cancers, and to treat some bladder, throat, thyroid and kidney cancers. When performed correctly by well-trained surgeons in appropriate patients, robot-assisted procedures have the potential to prevent some short-term complications, such as blood loss, and to reduce the length of hospital stays compared with open surgery.

, or RFA, is an outpatient procedure that uses heat delivered through a thin, needle-like probe inserted into the tumor to kill tumor cells. 

 is a similar procedure that uses rapid freezing and thawing to kill the cancer cells.

Radiation therapy is used alone to treat some cancers, but most often in combination with other therapies to improve the cure rate after surgery. Radiation could also be used to allow less extensive surgery or to relieve side effects of advanced cancer. High doses of radiation can cause side effects after treatment, as well as late effects, such as secondary cancers. Newer specialized techniques more accurately target radiation to tumors and minimize these effects.

 radiates the cancer cells directly by implanting radioactive seeds or wires into the body in or near the tumor. Brachytherapy is used in prostate, cervical and other cancers. Brachytherapy can also be used in breast cancer. This is a type of partial breast irradiation and is sometimes used for smaller, lymph node-negative, lower-risk breast cancers.

 contain radioactive elements that deliver radiation directly to tumors. These injections are approved to treat bone metastases in prostate and thyroid cancers, as well as some types of lymphoma, and to alleviate cancer-related bone pain; these drugs can also be delivered to tumors in the liver.

uses several weak radiation beams originating from different angles that intersect to produce a concentrated high dose of radiation at the tumor site. Advanced conformal therapy, such as intensity-modulated radiation therapy, uses multiple beams with varying intensity.

, such as Gamma Knife, uses a computer to simultaneously focus about 200 small beams onto a tumor in the brain while the patient’s head is immobilized in a special helmet. A similar technique, known as CyberKnife, bypasses the need for the helmet by using imaging to make adjustments for movements. Gamma Knife is used for small- to medium-sized tumors in the brain, and CyberKnife is employed for larger tumors and tumors in other areas of the body.

 uses positively charged particles, called protons, that only travel a certain distance. The method allows doctors to control the depth of radiation more precisely and deliver more of it to tumors while sparing nearby healthy tissue. Proton beam therapy is used for some childhood cancers and certain cancers of the brain, central nervous system, eye, head and neck, liver and lung, and some sarcomas. It’s also being investigated in breast, esophageal, prostate and other cancers. More research is needed to determine if side effects are less intense than with older types of radiation.

While surgery and radiation target the tumor, chemotherapy targets the whole body systemically through a number of mechanisms of action. New chemotherapy drugs are more effective and less toxic than agents developed 50 years ago, due to greater knowledge about how to deliver them, including optimal dose and frequency of dose, alone and in combination.

Chemotherapy can be given as the primary — or main — treatment for some cancers, such as lymphoma and leukemia. It can also be given after the cancer has been removed as adjuvant therapy, which might improve survival and delay or prevent disease progression. Neoadjuvant chemotherapy is given before surgery to shrink tumors enough to permit less extensive surgery. When cancer is not curable, palliative chemotherapy can often reduce symptoms caused by tumors and help people live longer.

 disrupt mitosis, a phase of cell division in which a cell duplicates and separates the chromosomes in its cell nucleus. Mitotic inhibitors include taxanes and vinca alkaloids (which are approved to treat some solid tumors, as well as lymphomas and leukemias) and epothilones (which are used to treat advanced breast cancer when taxanes no longer work). Mitotic inhibitors are known for their potential to cause peripheral nerve injury (neuropathy), a potential dose-limiting side effect.

are used to treat blood-related cancers, such as non-Hodgkin lymphoma, Hodgkin lymphoma, chronic leukemias and multiple myeloma, and are also effective in breast, lung, ovarian and some gastrointestinal cancers. Alkylating agents work by damaging the DNA of cancer cells to prevent them from dividing and multiplying. This group includes platinum-based chemotherapies.

 interfere with DNA and RNA production. They are effective in a specific cycle of cell growth and are used against leukemias, lymphomas and cancers of the ovary, breast, gastrointestinal tract and lung.

interfere with enzymes that are important for accurate DNA replication. They are used to treat certain types of leukemia, as well as colorectal, gastrointestinal, lung, ovarian and other cancers.

 are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. Anthracyclines treat a variety of tumors and work in all phases of the cell cycle. Because they can damage the heart muscle, anthracyclines have a lifetime dose limitation.

Bone marrow, the spongy material inside the bone, is the natural home for hematopoietic stem cells (HSCs), the “parent cells” that develop into different types of blood cells. These stem cells can be retrieved from either the patient (called an autologous transplantation) or a donor (an allogeneic transplantation). Patients who provide their own HSCs have them removed from the bone marrow or the bloodstream prior to chemotherapy and/or radiation, and the cells are frozen for later use. In other cases, the HSCs come from a donor, who might be an identical twin, another close relative (often a sibling), an unrelated person or even an unrelated newborn. Patients with leukemia, myeloma, low-grade lymphoma, myelodysplastic syndromes and, less often, various other cancers, might be treated with stem cell transplantation.

High doses of radiation and/or chemotherapy have the unwanted side effect of damaging a patient’s bone marrow stem cells. Transplantation restores the patient’s bone marrow. Over time, the infused cells divide and mature into cells normally produced by healthy bone marrow, a process known as engraftment. When donor cells mount an immune attack on residual cancer cells, the effect is called graft-versus-tumor.

Graft-versus-host disease, or GVHD, can occur after allogeneic transplantation if the donor immune cells view the recipient’s body as foreign. The recipient’s immune system has largely been destroyed by conditioning treatment and cannot fight back. The donor immune cells can attack certain organs (most often the skin, liver and gastrointestinal tract), which impairs the organs’ ability to function, while the required suppression of the immune system increases the chance of infection.

About one-third to one-half of patients who receive an allogeneic transplantation develop acute GVHD within 25 days (on average). Serious cases of uncontrolled GVHD, though uncommon, can be fatal.

Hormone therapies interfere with the interaction of sex hormones (androgens and estrogens) and some types of cancer, particularly breast and prostate. Hormone therapy can be used alone or with other treatments.

Following surgery, women with breast cancer that is shown to be fueled by estrogen are treated with an estrogen blocker and/or drugs called aromatase inhibitors. These drugs are taken for at least five years. Aromatase inhibitors block an enzyme that converts androgens to estrogens in postmenopausal women.

Patients with prostate cancer could receive androgen-deprivation therapy to lower testosterone levels. Another group of drugs, known as anti-androgens, are sometimes helpful if other hormone therapies stop working. Removing the ovaries or testicles can also reduce the level of sex hormones.

Researchers have learned more about specific molecular changes responsible for cancer growth, resulting in new drugs called targeted therapies. These drugs target genes or proteins in the cell. However, many of these newer agents must be combined with traditional chemotherapy, and some carry their own side effects, such as rash, diarrhea, heart malfunction or high blood pressure.

 prevent the formation of new blood vessels to the tumor (angiogenesis). Shutting down its blood supply shrinks the tumor, which needs nutrients and oxygen from blood to survive and grow. Most anti-angiogenic drugs target either a protein secreted by certain tumors to promote the growth of new blood vessels (called vascular endothelial growth factor, or VEGF) or the VEGF receptors on blood vessel cells.

 block enzymes with a variety of functions, including angiogenesis, growth factor receptors and other aspects of cell signaling, and are used in treating many types of cancer.

 treat multiple myeloma and mantle cell lymphoma by blocking multi-enzyme complexes called proteasomes. These molecules break down proteins involved in regulating cell processes relevant to cancer.

 block a key protein in cells that regulates cell growth and survival. These inhibitors block the translation of genes that regulate the cell cycle and reduce levels of certain growth factors involved in the development of new blood vessels, such as VEGF. mTOR inhibitors are currently used for breast, kidney, neuroendocrine and other cancers.

 block the activity of an enzyme that helps cancer cells repair their DNA when it’s damaged. This can cause the cells to die. Often, these drugs work well in cancers with inherited or acquired mutations to the BRCA genes, because these cancers already have DNA repair problems and the medications further interfere with that process. PARP inhibitors are used to treat breast, ovarian, pancreatic and prostate cancers.

 interfere with the activity of specific proteins to stop cancer cells from repairing their DNA when it’s damaged and change the way certain genes express themselves. This harms the ability of cancer cells to function, preventing them from growing and multiplying. These drugs are approved to treat multiple myeloma and T-cell lymphoma.

 are laboratory-manufactured versions of natural human antibodies, proteins made by the immune system to fight invaders such as cancer. Monoclonal antibodies are designed to seek out and bind to antigens, or markers, on the surfaces of cancer cells, thus stimulating the immune system to attack those cells. These drugs are approved to treat many cancer types, including breast, blood and colorectal.

 combine two kinds of drugs. One type are monoclonal antibodies, targeted immunotherapies that use natural substances or engineered alternatives to boost the immune system and fight cancer. They have been approved
by the Food and Drug Administration (FDA) for many types of cancer. Antibody-drug conjugates use a linker to attach one of these drugs to a potent chemotherapy agent. The antibody delivers the chemotherapy to cancer cells, and, once the drug is absorbed by the cells, the linker releases the chemotherapy. The FDA has approved this type of treatment for HER2-positive breast cancer and certain types of lymphoma.

Drugs that stimulate the body’s immune system to attack cancer are known as immunotherapies. In the pages immediately ahead, we explore immunotherapy types including checkpoint inhibitors and chimeric antigen receptor (CAR)-T cell therapy.

 are newer techniques. One of them, Optune, is approved to treat the brain cancer glioblastoma. Designed to be worn 18 hours a day, the device uses tumor-treating electromagnetic fields to prevent cancer DNA from dividing and multiplying.

A product called Quell is for cancer pain. It wraps around the calf and sends low-frequency electricity to sensory nerves, causing the brain to block pain signals.

Other wearable devices include scalp cooling caps, worn for a period of time before, during and after chemotherapy infusions to help prevent hair loss. Additionally, devices that may detect certain types of cancer are being studied.

NEOADJUVANT AND ADJUVANT TREATMENTS ENHANCE PRIMARY THERAPY


It is becoming more common for patients with cancer to get neoadjuvant and adjuvant treatments, which are given before and/or after the main therapy. These therapies are used in cancers including breast, lung, bladder, colon and ovarian.

Neoadjuvant treatments are often given before surgery to shrink a tumor so it is easier to fully remove. In some cases, the amount of shrinkage affects subsequent treatment decisions. The goal of adjuvant treatment is to prevent recurrence or spread by killing any cancer cells that linger after the primary treatment, which in many cases is surgery.

A number of treatments can be used as neoadjuvant or adjuvant therapies, including chemotherapy, targeted drugs, radiation and hormone-blocking medications. Immunotherapy is available as an adjuvant therapy and is being studied as a potential neoadjuvant treatment.

These before-and-after treatments are given when scientific evidence shows that they are likely to improve health outcomes based on the cancer’s type and stage. They are typically given to patients whose cancer has grown past the very earliest stage, so there is a risk it could leave cells behind after primary treatment, but not to the metastatic stage, meaning it has reached distant parts of the body. Patients with cancers driven by mutations associated with a high risk of recurrence might also benefit from neoadjuvant and/or adjuvant treatments.

Like primary treatments, these types of treatments can cause side effects, so patients should talk with a doctor about the types of therapies recommended, how much they are expected to lower risk of recurrence or cancer death, how they will affect daily life and for how long.

Proven approaches and new technologies mean individualized treatment.

Making Sense of Cancer Therapies

Immunotherapy is a rapidly evolving strategy that enlists the body’s own immune system to fight cancer. These treatments work by stimulating the production and activity of T cells and antibodies, which exist naturally in the body and have the ability to recognize and kill cancer cells.

Types of cancer that can be treated with immunotherapies approved by the Food and Drug Administration include melanoma, Hodgkin lymphoma, acute lymphoblastic leukemia, squamous cell carcinoma of the skin, and kidney, bladder, lung, prostate, breast, colorectal, liver, gastric, cervical, uterine, brain, pancreatic, esophageal and head and neck cancers. Immunotherapies are also being tested in other forms of cancer, including additional blood cancers.

Combinations of these drug types with each other, or with other anti-cancer therapies, may be more effective for some patients.

While immunotherapies don't cause the hair loss that comes with chemotherapy, they can spark nausea, rash, fever, chills, fatigue, diarrhea or even severe autoimmune reactions or endocrine hormone deficiencies. These drugs can also be very expensive.

So far, 20% to 30% of patients with immunotherapy-treatable cancers respond, and researchers are asking why, and figuring out how to make the most of the treatments. Some responses can be long-lasting or curative, so there is interest in refining this approach and expanding the number of patients and types of tumors that can be successfully treated.

Some cytokines, such as interleukins and interferons, which are found naturally in the body, can also be produced in the laboratory and given to patients to change the way their immune systems are regulated, potentially stimulating immune responses. These approved drugs are used to treat melanoma, kidney and bladder cancers, although they work only in a minority of those patients, and side effects can be severe.

While T cells have cancer-killing ability, they are normally held somewhat at bay by “inhibitory checkpoints” in the immune system. The job of these checkpoints is to keep the T cells from engaging in out-of- control activity. The problem with this system is that cancers can hide in the body by sending out the same signals as these checkpoints, along the cell-signaling pathways PD-1/PD-L1 or CTLA-4; this way, T cells don’t recognize or fight them.

One group of immunotherapy drugs blocks this kind of signaling so that the checkpoints no longer have a hold over the activity of T cells. This frees up the T cells to fight cancer. However, in doing so, the immune cells also attack some normal tissue, causing a variety of side effects.

Checkpoint inhibitors have been approved for the treatment of a variety of solid tumor types, and continue to be tested in clinical trials. They are also approved to treat any cancer, regardless of type, that is considered microsatellite instability-high, meaning that cancer cells are unable to repair their own DNA when it’s damaged.

When the immune system is provoked by foreign cells and other substances, it reacts by activating T-cell lymphocytes (a type of white blood cell), which can directly kill foreign cells, and by stimulating B-cell lymphocytes to make proteins called antibodies. These antibodies are drawn to other proteins known as antigens, which sit perched on the outsides of cells; drawn like magnets, the antibodies attach to the antigens. Once in place, the antibodies call in the immune system to destroy the cells to which they are attached.

Monoclonal antibodies, which are designed to seek and destroy specific cancer-associated antigens, can be made in a lab and then given to patients. Some of these strictly target one type of antigen, but cannot always fight tumors on their own. Bispecific antibodies may be more effective, because they can bind to, and destroy, two different antigens present on one or many cells. One antibody enlists a T cell while the other targets a tumor, bringing the main partners of the immune process together.

If a good immune response is already happening in a patient’s body, adoptive T-cell therapy may improve it. In adoptive cell transfer, a sample of a patient’s tumor is sent to a lab, where T cells inside the tumor are removed and stimulated to recognize a tumor surface protein and increase in number. Then, this larger group of T cells, known as tumor infiltrating lymphocytes, is returned to the patient intravenously. This experimental method has been shown to induce complete, durable regression of certain malignancies, including a number of blood cancers and melanoma.

Like adoptive T-cell therapy, chimeric antigen receptor (CAR) therapy involves manipulating a patient’s T cells in a lab. But in this case, the T cells are genetically modified to express a specific surface receptor, which prepares them to hone in on, and attack, specific proteins on a particular kind of cancer cell. When the CAR T cells are infused into the patient’s body, they can multiply and continue to eradicate tumors over time. Currently, there are two CAR-T cell therapies approved in the U.S. One is for advanced or recurrent acute lymphoblastic leukemia in children and young adults. The other is for certain types of advanced or recurrent non-Hodgkin lymphoma. Clinical trials have shown that this method can also have significant anti-tumor activity in neuroblastoma and chronic lymphocytic leukemia, and trials are exploring CAR-T cell therapy in an array of solid tumors and blood cancers that affect both children and adults.

CAR-T cell therapy is carried out in the hospital, where patients are monitored closely for side effects, particularly the immune system’s potential attack on healthy organs.

A host of vaccines, some approved and some experimental, also fall into the immunotherapy category. There are four main basic types:

 to deliver an agent such as a cytokine that can cause the destruction of cancer cells.

 into the body with the goal of drawing the immune system’s attention to the foreign cells so it will fight them — as well as the tumor cells already growing in the body.

, which are made uniquely for each patient using his or her own white blood cells, mixed with an agent that will help the body mount an immune response against cancer cells.

. These include a small peptide (amino acid) sequence taken from a tumor-associated antigen. This is mixed with an agent that stimulates dendritic cells to process the peptide sequence; in turn, that causes the immune system to recognize and fight any antigens that contain the sequence.

Understanding how the immune system controls itself has led to impressive treatment gains.

Delving Into Immunotherapy

Clinical trials provide data that prove whether a new treatment is better than the standard therapy. They could offer alternatives if patients have few treatment options or if they’re seeking a treatment with the potential of being more beneficial than the standard treatment. Choosing a clinical trial might mean patients can find an option with fewer toxicities than the one being offered or one that is more convenient, such as an oral medication or one with a shorter treatment time. Although an increasing number of investigational cancer drugs are being approved by the Food and Drug Administration (FDA) each year, the process is still lengthy and complex. If patients can navigate the process, they might find a good option, but it’s important to understand the phases involved in clinical trials and the potential benefit.

 are the first to move a drug out of the laboratory and into people. Their goal is to determine how the body handles a specific drug. These trials are very small, including only 10 to 15 people, usually healthy individuals.

 enroll a small number of patients with diverse tumor types to study side effects and establish a safe dosage for a potential treatment, usually by increasing the dose serially and observing for side effects. Phase 1 studies also evaluate how a new treatment should be given (for example, if a new drug is best taken orally or injected into the bloodstream or muscle), how often it should be administered and the most effective dose with the fewest or least severe side effects. Most patients who enter phase 1 trials have limited treatment options or do not improve with standard therapies. This phase is not designed to determine the effectiveness of the treatment.

 continue to test the safety of a treatment while beginning to evaluate how well it work, sometimes in combinations with approved drugs. These trials are usually limited to a specific cancer that showed benefit with the treatment in earlier trials.

 compare the experimental drug, combination of drugs, regimen of radiation therapy or surgical procedure with the current standard to determine if it is better. Enrollment is often in the hundreds to thou- sands across multiple locations. Typically, a participant is randomly assigned to the standard treatment or the new treatment (called randomization). Patients who are not randomized to the experimental treatment will receive identified standard treatments.

are sometimes referred to as real-world studies, because they illustrate how a drug works outside of a strictly regulated clinical trial. Some, but not all, of these trials occur after a drug has been approved by the FDA. Some goals of phase 4 trials are to learn more about a drug’s effectiveness, safety and side-effect profile. These trials also help determine how the medication works when given alongside other treatments, how it compares to other therapies on the market and whether or not it is cost-effective. Phase 4 investigations are large, including several hundreds or thousands of patients.

Compassionate drug use is the use of a new, unapproved drug to treat a seriously ill patient when no other treatments are available.

Many people with life-threatening diseases can’t find suitable clinical trials. This might be because they live too far from cancer research centers where the studies are being done, or because they’re not eligible for some reason.

People who aren’t in clinical trials might be able to get access to an unapproved drug from the company that makes it in two ways:

. In general, EAPs are for patients who meet all of these conditions: 

Have a serious and life-threatening condition.

Are not eligible for any current clinical trial that’s using the drug.

Have no other comparable treatment options.

Are likely to experience benefits that outweigh the risks involved.

The FDA approves or denies EAP requests based on available reports from the company sponsoring the drug in clinical trials, including safety information and data about how the drug may treat cancer. To learn more, see the FDA’s information about EAPs at 

 “Right to try” came about when a federal law was passed in 2018 that allows patients another path to access unapproved drugs, without needing the review and approval of the FDA. “Right to try” laws do not replace EAPs, but provide another way to possibly be able to access unapproved drugs.

It’s important to understand that “right to try” does not actually give patients the right to try any unapproved drug. Instead, it gives them the right to request access to an unapproved drug from the company that makes it, without having to go through the FDA.

Bypassing the FDA does not necessarily mean that such access will be granted. To be eligible for “right to try,” a person must:

Be diagnosed with a life-threatening disease or condition. 

Have tried all approved treatment options for the disease or condition.

Be certified by a doctor to be unable to participate in a clinical trial for the investigational drug.

Give written informed consent that he or she understands the risks of taking the investigational drug. 4Receive permission from the maker of the drug and approval from the institutional review board of a plan to administer and monitor effects from the drug.

To learn more, see the FDA’s information about “right to try” at fda.gov/patients/learn-about-expanded- access-and-other-treatment-options/right-try.

Before enrolling in a clinical trial, patients are asked to sign an informed consent document that states they understand the purpose of the research, its risks and benefits, the study procedures and their rights as patients. Patients should keep a copy of the informed consent document with their medical records. No informed consent document can ask patients to waive their legal rights or release the trial’s research team, trial sponsor, drug manufacturer or institution from liability for negligence.

Patients are allowed time to discuss the informed consent documents with family, friends or their physicians and to ask follow-up questions of the research team. As the trial progresses, the research team will continue to provide information and updates. It is important to understand that because the treatment is experimental, the outcomes and side effects are not always foreseeable, although any predicted risks should be explained in detail beforehand.

Patients should discuss the costs associated with the trial with the research team and ask what would be covered by insurance. In most trials‚ the therapy under investigation is provided at no cost to the participant. Routine costs, such as hospital stays, outpatient appointments and tests done during a trial, are often covered by insurance or Medicare if the trial meets certain criteria.

A provision in the Affordable Care Act, effective in 2014, prohibits new health plans from denying coverage for routine care that the plan would otherwise provide just because a person with cancer is enrolled in a clinical trial. The law also prohibits insurers from dropping coverage because a person chooses to participate in a clinical trial. Patients considering a clinical trial might also want to calculate the cost of travel and lodging if the site of the trial is distant, especially if the trial extends over several weeks or months and frequent trips are needed. Some institutions and nonprofit organizations can help with certain expenses for travel and housing (visit curetoday.com/journey).

No single resource lists every clinical trial, but ClinicalTrials.gov is the most comprehensive and allows searching by tumor type, drug type, location and other factors. The process might involve searching the web, calling pharmaceutical companies or asking a doctor or cancer center for information. Patient advocacy groups can also help patients find appropriate trials.

Patients should begin with their oncologist‚ who not only can tell them if something is available locally‚ but also give them resources on what is happening in other parts of the country. Although it could be time-consuming to search for clinical trials at each location, patients will probably want to start with facilities closest to home. Those who are looking for a particular drug might want to contact the pharmaceutical company directly for the best information.

Fewer trial locations will be available for drugs in early- phase testing, so patients might have better luck with late-phase trials, which are conducted in multiple sites across the country.

Each trial has its own eligibility criteria and often has restrictions based on the type and stage of cancer‚ age of the patients‚ previous treatments received and current health status. Patients should have their medical histories accessible when searching for clinical trials because eligibility requirements could disqualify them from participating. Once they have found a number of trials for which they possibly qualify, patients should discuss them with their doctors and contact the study coordinators.

What patients need to know when deciding whether a clinical trial is right for them.

Understanding Cancer Clinical Trials

Once patients are aware that clinical trials are an option for cancer treatment, many have questions about whether this might be the right path for them. Blanca Ledezma of UCLA Health in Santa Monica, California, a nurse practitioner who holds a master’s degree in nursing, has some insights that can help patients decide. Here, she answers some top patient questions about the pros and cons of joining trials.

When and why should I consider joining a clinical trial?

Patients should ask about clinical trials as soon as they receive their diagnosis and are making their first treatment decisions. They should always know what trials are available to them and whether they want to take part. Perhaps there aren’t any trials that are appropriate for them, but at least they’ve asked and providers know they are interested.

Some patients find it worthwhile to participate in trials because it means they will get a novel agent that could be more effective than standard care alone (Standard, or standard-of-care, treatment is approved by the Food and Drug Administration — the FDA — and widely recommended for use for patients with a particular condition). This may especially be of interest to patients with cancers for which there are few standard treatments or none that are very effective. Patients may also feel good knowing they are contributing to research that could help others in the future. 

How will I know if I’m eligible for a clinical trial?

For a trial to be appropriate for an individual, that patient must meet its eligibility requirements. These can include having a specific cancer or one that is associated with a certain genetic mutation, having cancer that is a certain stage, being within a specified age range, meeting a certain level of healthiness and ability to complete the daily activities of living, and having had or not had certain treatments in the past.

What kinds of drugs would I take in a clinical trial?

Trials can test targeted agents or immunotherapies, which are now available in numerous cancer types and are being tested in even more. They may also test chemotherapies, new classes of drugs, combinations of medications or medical devices.

These types of drugs work in different ways. For instance:

Chemotherapy affects cells that are rapidly growing and dividing; this includes cancer cells but also some healthy cells.

Targeted drugs home in on cells affected by a specific genetic mutation that drives cancer. Typically, they stop the activity of cancer-causing proteins that are made by the body due to such mutations. This means that targeted drugs mainly affect cancer cells.

Immunotherapy stimulates the body’s own immune system to fight cancer.

Both targeted drugs and immunotherapies have changed the landscape quite significantly for certain disease types for which there wasn’t much treatment to begin with. Now, we’ve been able to give patients more treatments, either alone or in combination with other therapies, that are personalized to their specific disease types, and they’re doing better than they have in the past.

Unfortunately, none of these drugs are free from side effects. Chemotherapy can cause fatigue, nausea, vomiting, diarrhea, hair loss, mouth sores and low blood counts that can lead to infection. Targeted drugs can cause diarrhea, liver problems and rash and interfere with blood clotting and wound healing. Immunotherapies can cause fatigue, nausea, rash and, less often, problems in organs including the lungs, liver, kidneys, intestines and glands that make hormones.

Why is molecular profiling important prior to a clinical trial?


In standard treatment or clinical trials, molecular profiling of a patient’s tumor is essential. Many targeted drugs and immunotherapies work by targeting a specific genetic mutation and counteracting its cancer-causing activity. Generally, these drugs won’t work well, or at all, unless the cancer has these mutations, so it wouldn’t make sense to give them without first testing tumor tissue or cancer cells found in blood to determine which genetic alterations are present.

In standard treatment, having this genetic information can help doctors decide which therapies to give and the order in which to administer them to maximize the options available.

When there are no FDA-approved treatments that target certain mutations, clinical trials of novel drugs can be especially helpful, although the efficacy of such medications can never be certain until these studies have been concluded.

Because knowing all a tumor’s treatable mutations is so crucial in terms of picking therapies, it’s very important at diagnosis for patients to wait until all molecular test results have come back before choosing a course of treatment.

If I join a trial, is it possible I will get a placebo instead of real medicine?


In trials for patients with metastatic cancer, participants would never get just placebo but would always get some treatment — in many cases the current standard of care. Giving these patients nothing would be unethical.

If it’s a trial of an adjuvant drug (given after the primary treatment) for earlier-stage disease, and it’s not standard practice to give any therapy after the main treatment for a particular cancer, in that case there is a possibility that a treatment arm may consist of placebo alone.

How can I know if a trial drug will work for me?

Once patients are found to be eligible to take a drug, the only way to know if it is going to work is by trying it and that’s true in standard-of-care therapy and in clinical trials. The difference is that we have data from studies of standard-of-care drugs and know, based on this data, that a treatment has been shown to have a certain efficacy for a particular disease type. In a clinical trial, we’re trying to develop (those) data so we can have more treatment options for patients.

Like standard-of-care patients, those in studies are followed with scans to evaluate their response to treatment.

How can I weigh the pros and cons of enrolling in a trial?

Trials are something many patients are open to because they gain access to a new novel agent that is not otherwise available to them. They get the added benefit of being followed very closely.

On the other hand, some patients may say, “I’m working and trying to maintain normalcy, and that doesn’t work for me,” because being in a trial generally requires a greater time commitment than get- ting standard treatment. We always have to consider the patient, their current situation, their desires and their current physical state.

We inform patients that trials are voluntary and that we don’t want to make them feel pressured to enter or stay in a trial. At the end of the day, they should do what they feel is the best decision for them.

How can I learn about clinical trials that might be right for me?

First, it’s important that patients educate and empower themselves and really understand their disease and the available treatment options. Providers will have a detailed discussion with patients regarding treatment options, including standard of care and possibly clinical trials. If patients have further questions regarding treatment options, they should contact their oncologists.

Patient advocacy groups can be of benefit in providing information about available treatments, as long as they’re reputable organizations such as the American Cancer Society, CancerCare, Cancer Support Community and disease-specific groups including the American Lung Association, the Prostate Cancer Foundation, the Multiple Myeloma Research Foundation and the Cholangiocarcinoma Foundation. Some patients may want to seek a second opinion to make sure they’re aware of all their options. Clinical treatment guidelines written by the National Comprehensive Cancer Network (nccn.org/patients/guidelines/cancers.aspx) specifically for patients can also be helpful in spelling out what standard treatment should consist of.

Those who want to learn about clinical trial options can ask their doctors, nurse navigators or other members of their health care teams for suggestions about trials that may be appropriate for them. Some practices run trials and can enroll patients; others don’t offer trials, but may refer patients to other institutions that do.

To search on their own for trials, patients can go to ClinicalTrials.gov and search by disease type and/or drug type. Some patient advocacy groups have searchable online databases of clinical trials, and some offer navigators at no cost who can help patients find trials.

Is a Clinical Trial Right for Me?

It is important to have and keep good medical insurance. Many patients have private insurance through employee group plans or individual plans. There are several types of health insurance plans, so it’s essential for patients to become familiar with their individual insurance plans and their provisions to know what they will have to pay for themselves.

This information can be found in the Summary of Benefits and Coverage that can be obtained from the patient’s insurance administrator at work or from the company that sold the individual policy. As of 2014, individual policies can be purchased in each state’s insurance marketplace without regard to pre-existing conditions.

Another option to consider is supplemental insurance, which pays a fixed amount for each day a person is hospitalized. There is usually a limit on the total number of hospital inpatient days that are covered in a calendar year. Supplemental policies are often used to pay for medical expenses not covered by the insurance plan or other expenses that might come up during an illness, but are really only helpful if patients already have health insurance coverage to cover the bulk of their health care costs. The money received from this type of policy can be used however a policy holder wishes. It is often used for the other expenses that families face when one member is ill.

KEEPING RECORDS OF HEALTH INSURANCE AND MEDICAL CARE

Keeping accurate records of medical bills, insurance claims and payments will help families manage their resources and reduce stress. Record-keeping is also important for those who wish to take advantage of the deductions available in filing itemized tax returns. The Internal Revenue Service (irs.gov) can provide information and free publications regarding tax exemptions for cancer treatment expenses.

Medical bills from all health care providers.

Reimbursements and explanations of benefits.

Dates, names and outcomes of contacts made with insurers and others.

Non-reimbursed or outstanding medical costs and copayments.

Meals, lodging and travel expenses, including gas.

Cellphone or telephone expenses related to medical or other types of care, including psychosocial.

Admissions, clinic visits, lab work, diagnostic tests, procedures and treatments.

Decide who will be the record-keeper or how the task will be shared.

Seek the help of a relative or friend. This could be especially important for people who live alone.

Set up a file system in a file cabinet, drawer, box or three-ring binder.

Check all bills and explanations of benefits for accuracy.

Review bills promptly after receiving them.

Save and file all bills, payment receipts, records of checks and proof of online payments.

Keep a daily log of events and expenses; a calendar with space for writing is useful.

Maintain a list of phone numbers for cancer care team members and other contacts.

Handling a Claim Denial or Refusal to Cover a Prescribed Service

It is not unusual for particular claims to be denied or for insurers to say they will not cover a test, procedure or service ordered by a patient’s doctor. If this occurs, it is important to have a working relationship with a case manager who can discuss the situation.

First, patients should ask their doctors to write a letter explaining or justifying what has been done or requested. Then, patients should resubmit the claim with a copy of the denial letter and the doctor’s explanation. Sometimes the test or service will need to be “coded” differently.

 If challenging the denial in this way is not successful, then patients might need to:

Postpone payment until the matter is resolved.

Ask to speak with a supervisor who has the authority to reverse a decision.

Seek help from the consumer services division of the state insurance department or commission.

Patients should make sure they keep originals of correspondence. The cancer care team or doctor’s office staff might help make copies if needed. Also, patients should keep a record of dates, names and conversations they have about the denial.

Patients who are uninsured could qualify for financial help to buy a health plan sold on their state’s health insurance marketplace. If their income is below a certain level, they might be eligible for coverage through Medicaid (eligibility varies by state). Some states have chosen to broaden access to Medicaid coverage under the health care law, while others have not. Patients can search for plans at healthcare.gov from Nov. 1 to Dec. 15 each year, or outside that window if they have experienced a major life event, such as job loss.

Those who are uninsured can also speak with hospital social workers, who may be able to help find funding for treatment.

Strategies can help patients get the most out of their health care coverage.

Handling Insurance Matters Related to Cancer