Adjuvant chemotherapy is a cancer treatment that is administered after a primary cancer treatment has been given. It is used to reduce the chance that the primary tumor will return or to kill cancerous cells that may have escaped primary treatment. The overall goal of adjuvant chemotherapy, as with most curative cancer treatments, is to increase the chance of disease-free survival.
Perhaps the best way to understand adjuvant chemotherapy is the way in which it is most commonly used: after cancer removal surgery. In the case of breast cancer, for example, the surgeon will remove the diseased breast tissue along with some surrounding tissue and the lymph nodes that drain fluid from the affected area. If there is any possibility that cancer may have spread from the primary tumor, whether the lymph nodes show evidence of metastatic disease or not, adjuvant chemotherapy may be indicated. While surgery is a local treatment, adjuvant chemotherapy extends to most areas of the body (with the possible exception of the brain and testes) and kills any cells that may have escaped from the primary tumor.
Adjuvant chemotherapy is administered shortly after the primary cancer treatment. There is no optimal timing for this therapy, but most oncologists agree that adjuvant chemotherapy is best given between two to eight weeks after surgery. The initial two week waiting period allows patients to heal after surgery; however, treatment is not delayed past eight weeks, usually. While it is not known how long one can wait to administer adjuvant chemotherapy and still achieve the desired effect, it is generally believed that waiting six months to a year is probably too long.
Chemotherapy that follows radiation may also be called adjuvant chemotherapy. Examples in which adjuvant chemotherapy is used after radiation treatment include the treatment of nasopharyngeal cancer (upper throat cancer) and medulloblastoma (brain tumor). More often, chemotherapy is administered at the same time as radiation therapy. Alternatively, chemotherapy may precede radiation therapy. In this case the chemotherapy is more correctly termed neoadjuvant chemotherapy.
As more studies emerge, it is apparent that when thoughtfully applied, adjuvant chemotherapy can reduce cancer-related symptoms, improve overall treatment outcomes, suppress recurrent disease, and improve survival. Some examples of cancers in which adjuvant chemotherapy has shown increased patient survival include breast, endometrial, cervical, colon, gastric (stomach), and lung, among others. It is not appropriate to use adjuvant chemotherapy for all stages of each of these cancer types, however. For example, adjuvant chemotherapy is standard of care in the treatment of Stage II non-small cell lung cancer (NSCLC) or higher, but has not yet been shown to be of any benefit in Stage I NSCLC. Therefore the decision to use adjuvant chemotherapy is not based solely on cancer cell type.
The first guiding principle in chemotherapy is the same as it is for any medical intervention, do the rewards outweigh the risks? This same concept guides the choice of when to use adjuvant chemotherapy-the beneficial outcomes must outweigh the potential side effects. This information is obtained through large clinical trials. For instance, a large group of people with limited small cell lung cancer are randomly assigned to one of two groups, a group that receives a specific type of adjuvant chemotherapy or a group that does not. Both groups receive the standard primary cancer treatment. If patients in the adjuvant chemotherapy group enjoy fewer disease symptoms, longer survival, and/or less disease burden, adjuvant chemotherapy might be considered in all patients with limited small cell lung showing the same characteristics.
While the use of adjuvant chemotherapy is tailored to each particular patient based on clinical studies, a current area of research is to customize treatment even further. Since adjuvant chemotherapy usually follows surgical removal of some or all of the cancer, pathologists are able to perform a number of histological, biochemical, and molecular tests on the tumor itself. Therefore it is reasonable to assume that the type of adjuvant chemotherapy can be selected based on the specific type of tumor. Thus instead of relying on the stage of cancer to guide treatment, histological grade and molecular and genetic markers could point to even more effective adjuvant chemotherapy with perhaps lower doses and fewer side effects.
Neoadjuvant chemotherapy is the administration of chemotherapy before the main or primary cancer treatment. The main goals of neoadjuvant chemotherapy are to make the tumor more manageable for future oncological interventions and to reduce the risk of metastasis. As with adjuvant chemotherapy, neoadjuvant chemotherapy is generally used prior to tumor removal surgery. For example, a short course of chemotherapy is administered to decrease the size (debulk) the tumor prior to surgery. Debulking is especially important in cases where the tumor has multiple, fingerlike projections and/or has grown deeply and intimately with the surrounding tissue. With a smaller and less intercalated tumor, the surgeon is able to remove less tissue overall, both cancerous and healthy.
The decision to use neoadjuvant chemotherapy in a particular patient depends mostly on information gained from radiological studies (e.g. PET, mammogram, CT, and MRI) and occasionally the results of a biopsy. Another major factor that influences the decision to use neoadjuvant chemotherapy is whether the tumor is easily resectable in its pretreated state. In other words, can the tumor be made smaller or more easily removable through the use of chemotherapy before surgery? If the answer is yes (or likely yes), neoadjuvant chemotherapy is usually indicated. This may reduce the functional and cosmetic damage caused by tumor removal surgery. Neoadjuvant chemotherapy may be particularly useful in treating cancers of the breast, colon, and lung.
Neoadjuvant chemotherapy is also used if it is believed that early chemotherapy will decrease the chance of local metastasis. Consider the steps involved in tumor removal: the surgeon must locate the tumor, dissect it, remove surrounding tissue, and relevant lymph nodes. If the tumor is large and the cancer cells are not stably affixed to the tumor, the chance of dislodging cancer cells and causing metastasis during surgery can be unacceptably high. When there is a risk of this occurring, neoadjuvant chemotherapy is often used to destroy some of the tumor cells and to reduce the risk of dislodgement during surgery.
Another application of neoadjuvant chemotherapy is to infuse radiosensitizers prior to radiation treatment. A radiosensitizer is a chemical that makes ionizing radiation more lethal to cells. Examples of neoadjuvant chemotherapy that can also act as radiosensitizers include cisplatin, paclitaxel, topotecan, irinotecan, and vinorelbine, among others. When these radiosensitizers are administered prior to radiation therapy, the overall dose or duration of radiation is less. This significantly reduces the occurrence of side effects from ionizing radiation.
One issue regarding neoadjuvant chemotherapy that needs to be considered is the risk of debilitating side effects. While the side effects that occur with any chemotherapeutic agent are a function of the type of drug used, the dose, and the duration of therapy, the side effects caused by neoadjuvant chemotherapy need to be followed closely. It would be considered unacceptable for the side effects of neoadjuvant chemotherapy to be so great as to interfere with the primary cancer treatment. In other words, if the neoadjuvant chemotherapy renders the patient unfit for surgery, it would actually do harm than good. Therefore the doses of neoadjuvant chemotherapy are usually lower than they would be in primary or even adjuvant chemotherapy. Also, the medications used are carefully chosen to be as least toxic to the patient as possible.