This Battle Which I Must Fight
Cancer in Canada's Children and Teenagers

ABOUT TREATMENT

HOW IS CANCER IN CHILDREN AND TEENAGERS TREATED?

The role of surgery is to obtain enough tumour tissue to make a precise diagnosis and, if indicated, to remove as much tumour as possible, either initially or following chemotherapy. Radiation and chemotherapy kill cancer cells by interfering with their ability to grow and reproduce. Radiation is delivered specifically to the region where the disease is located and exerts its effect in that region; in contrast, chemotherapeutic drugs given by mouth or injection are distributed throughout most of the body.

Most types of childhood cancer are treated with chemotherapy from the outset, even when the tumour has been removed completely and there is no evidence that cancer cells have spread elsewhere. This is because spread of the disease cannot always be detected.

There are several classes of chemotherapeutic drugs, with many drugs in each class. Each class of drugs affects cancer cells in a particular way, and specific drugs are most effective against particular cancers. Usually, chemotherapy drugs from different classes are used in combination, so that cancer cells are attacked in more than one way. This decreases the likelihood that cancer cells will become resistant to one or more chemotherapy drugs.

Most chemotherapy drugs administered by mouth or injection do not reach the brain and meninges (membranes covering the brain) where cancer cells may grow. Therefore, it may be necessary to inject drugs directly into the cerebrospinal fluid which bathes the brain and spinal cord and/or to irradiate the brain and spinal cord. This is particularly the case when a young person has leukemia or non-Hodgkins lymphoma.

Patients are monitored closely to prevent, detect, and manage side effects of chemotherapy. Some of the temporary side effects relate to the fact that, in addition to affecting cancer cells, the drugs also damage rapidly dividing normal body cells. The most rapidly dividing normal cells in the body are in the bone marrow, gastrointestinal tract, and hair follicles. Temporary side effects of chemotherapy include lowering of blood cell counts, infection, bleeding, sores in the mouth and bowel, hair loss, nausea, vomiting, fatigue, bone pain, alterations in mood, and changes in appetite.(32,85,98,99) Each chemotherapy drug has its own list of possible side effects. Fortunately, most of these drug-specific side effects are temporary; they disappear as the body's own healing mechanisms repair the damage done to normal tissues and as the drugs are cleared from the body. However, some effects of chemotherapy drugs are life-threatening or permanent and are described later in this book under late effects.

General side effects of radiation therapy include fatigue, decreased appetite, and redness of the skin in the treatment field. The severity and type of side effect depend upon the body site being treated, the radiation therapy dose and other factors. For example, superficial or deep tissues within the radiation field may become inflamed. Radiation to the head may cause headache, nausea, vomiting or temporary hair loss. Nausea, vomiting and diarrhea may result from radiation to the abdomen. If the treatment field encompasses a large volume of bone marrow, the blood cell counts may drop.

Bone marrow transplantation is a procedure used as supportive treatment for some children and teenagers with leukemia, lymphoma or solid tumours. Bone marrow is the spongy, red tissue in the centre of bones. It is where blood cells are formed from very young cells called stem cells. Intensive chemotherapy can injure the bone marrow, leaving it permanently unable to make blood cells. A bone marrow transplant restores the bone marrow.

Bone marrow is collected by a process called harvesting. Usually bone marrow is removed from the hip bones, where there is an abundance of stem cells. It is then injected into the patient intravenously like a blood transfusion. The transfused stem cells travel via the blood stream to the centres of the bones, where they begin to produce normal blood cells.

There are two main sources of bone marrow for transplantation. Autologous bone marrow is the patient's own marrow that was removed when the disease was in remission. The marrow is sometimes treated to try to destroy any remaining cancer cells. It is preserved and then infused back into the patient when needed. Allogeneic bone marrow comes from a donor who is genetically compatible with the patient. This person may be a family member - usually a sibling - or an unrelated person who is selected from an international bone marrow donor registry.

The bone marrow source depends upon the type of cancer, the course of the disease, and the availability of a good match. An allogeneic transplant is preferred for treating children and teenagers with leukemia, provided a good match is available. This is because the cells from a donor not only repopulate the bone marrow, but also attack the tumour cells.

The side effects of transplantation depend on the type of cancer being treated, as well as the type of transplant.(140) Pre-transplant chemotherapy results in more extreme - sometimes life-threatening - side effects than occur with lower chemotherapy doses. These side effects can include infection, hemorrhage, mouth sores, severe bowel disorders, skin breakdown and liver complications. In addition, patients who undergo allogeneic transplants can experience graft-versus-host disease, whereby the donor's cells attack the patient's organs and tissues. The symptoms and severity of graft-versus-host disease vary and are treated with drugs. The risk of graft-versus-host disease is lessened by a good match between the patient and the donor. Although many of the side effects of transplantation are short-lived, some may be prolonged or permanent. The intensity of the therapy also can induce emotional and psychological problems in the child and family members. Nevertheless, most families feel that the possibility of a cure justifies the risks associated with the procedure.(10,15)

In some instances, bone marrow transplantation can be replaced by a technique called peripheral stem cell transplantation in which either autologous or allogeneic stem cells are harvested from the blood stream. Since stem cells are rare in blood, the donor is given a growth factor drug called G-CSF (granulocyte-colony stimulating factor) which stimulates the stem cells to migrate from the bone marrow into the blood stream. Blood is removed from the donor and the stem cells are separated from other blood cells. The stem cells are then given to the patient by intravenous infusion. Peripheral stem cell transplants may have advantages over bone marrow transplants in that stem cells are easier and less painful to obtain from donors, the number of stem cells that can be harvested is greater, and blood cell recovery is generally more rapid. However, clinical trials comparing peripheral stem cell transplant with bone marrow transplant are needed to provide clear evidence of the superiority of one method over the other.

HOW HAVE TREATMENTS EVOLVED?

Until all children and teenagers with cancer can be cured--with minimal short- and long-term side effects - there is room for improvement. Therefore, ongoing research into better ways to treat children and teenagers with cancer is required. This research has several aims: to improve disease-free survival and cure rates; to reduce the occurrence and severity of the short- and long-term side effects of treatment; to understand more about the biology of the different types of cancer; to identify factors which affect outcome and indicate the need for more or less intensive treatment; and to preserve quality of life.

Since childhood cancer is not common, clinical research to find even more effective treatments is conducted in collaboration with international childhood cancer groups. There are currently two major collaborative groups based in North America - the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG). These and other groups collaborate on studies of specific childhood cancers. Most Canadian childhood cancer treatment centres belong to one of these study groups (Appendix 3).

As a result of research, treatments for children and teenagers with cancer are continually improving. New treatment protocols are designed to test new approaches to treatment. A treatment protocol is a detailed set of instructions about what and how treatments are to be administered. It may be either standard (proven to be effective) or new (currently being tested to determine whether it is better than the standard treatment). Treatment protocols are tailored both to the biologic properties of the disease, such as its type and stage, and to characteristics of the child or teenager, such as age. Among other things, these protocols specify the drugs to be administered, their dosages and frequency and the tests that monitor toxicity and response. Studies that compare the effectiveness and side effects of a new treatment protocol to the effectiveness and side effects of the standard or previous best treatment protocol are called Phase III studies or clinical trials.

Once a family agrees to participate in a phase III trial, a process called randomization (random assignment) may be used to determine which treatment protocol the child will receive. Some families dislike the idea of randomization because they expect their physician, in consultation with them, to have sufficient knowledge to choose the best treatment for their child; however, clinical trials are only carried out when it is not known which treatment will be better for the child. Assigning treatments in a randomized fashion ensures that treatment selection is not influenced by factors, such as emotions and preferences not based on factual knowledge, that could bias the results and lead to the wrong conclusion about treatment effectiveness. If, according to predetermined criteria, a treatment protocol emerges as superior or inferior during the study, random assignment is stopped and all children are treated with the more effective protocol. Tremendous progress in the understanding and treatment of childhood cancers has occurred because of this process.

In addition to Phase III studies, two other types of scientific investigation are conducted. In Phase II studies, the optimal dose of a new drug is administered to patients with cancers that are refractory (resistant) to the more standard therapies to determine the response rate to this drug. Patients in relapse may participate in a Phase I study that tests newer drugs for which optimal doses have not yet been determined. The purpose of Phase I studies is to identify the maximum dose of a new drug that can be tolerated, and to observe the response of the disease.

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