Adjuvant therapy
Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.
An adjuvant used on its own specifically refers to an agent that improves the effect of a vaccine. Medications used to help primary medications are known as add-ons.
History
The term "adjuvant therapy," derived from the Latin term adjuvāre, meaning "to help," was first coined by Paul Carbone and his team at the National Cancer Institute in 1963. In 1968, the National Surgical Adjuvant Breast and Bowel Project published its B-01 trial results for the first randomized trial that evaluated the effect of an adjuvant alkylating agent in breast cancer. The results indicated that the adjuvant therapy given after the initial radical mastectomy "significantly decreased recurrence rate in pre-menopausal women with four or more positive axillary lymph nodes."The budding theory of using additional therapies to supplement primary surgery was put into practice by Gianni Bonadonna and his colleagues from the Instituto Tumori in Italy in 1973, where they conducted a randomized trial that demonstrated more favorable survival outcomes that accompanied use of cyclophosphamide methotrexate fluorouracil after the initial mastectomy.
In 1976, shortly after Bonadonna's landmark trial, Bernard Fisher at the University of Pittsburgh initiated a similar randomized trial that compared the survival of breast cancer patients treated with radiation after the initial mastectomy to those who only received the surgery. His results, published in 1985, indicated increased disease-free survival for the former group.
Despite the initial pushback from the breast cancer surgeons who believed that their radical mastectomies were sufficient in removing all traces of cancer, the success of Bonadonna's and Fisher's trials brought adjuvant therapy to the mainstream in oncology. Since then, the field of adjuvant therapy has expanded to include a range of adjuvant therapies to include chemotherapy, immunotherapy, hormone therapy, and radiation.
Neoadjuvant therapy
, in contrast to adjuvant therapy, is given before the main treatment. For example, systemic therapy for breast cancer that is given before removal of a breast is considered neoadjuvant chemotherapy. The most common reason for neoadjuvant therapy for cancer is to reduce the size of the tumor so as to facilitate more effective surgery.In the context of breast cancer, neoadjuvant chemotherapy administered before surgery can improve survival in patients. If no active cancer cells are present in a tissue extracted from the tumor site after neoadjuvant therapy, physicians classify a case as "pathologic complete response" or "pCR." While response to therapy has been demonstrated to be a strong predictor of outcome, the medical community has still not reached a consensus in regard to the definition of pCR across various breast cancer subtypes. It remains unclear whether pCR can be used as a surrogate end point in breast cancer cases.
Adjuvant cancer therapy
For example, radiotherapy or systemic therapy is commonly given as adjuvant treatment after surgery for breast cancer. Systemic therapy consists of chemotherapy, immunotherapy or biological response modifiers or hormone therapy. Oncologists use statistical evidence to assess the risk of disease relapse before deciding on the specific adjuvant therapy. The aim of adjuvant treatment is to improve disease-specific symptoms and overall survival. Because the treatment is essentially for a risk, rather than for provable disease, it is accepted that a proportion of patients who receive adjuvant therapy will already have been cured by their primary surgery.Adjuvant systemic therapy and radiotherapy are often given following surgery for multiple types of cancer, including colon cancer, lung cancer, pancreatic cancer, breast cancer, prostate cancer, and some gynaecological cancers. Some forms of cancer fail to benefit from adjuvant therapy, however. Such cancers include renal cell carcinoma, and certain forms of brain cancer.
Hyperthermia therapy or heat therapy is also a kind of adjuvant therapy that is sometimes given in combination with radiotherapy or chemotherapy to boost the effects of these conventional treatments in treating advanced cancers. Heating the tumour area sensitises it making it more responsive to the other therapies used. It is cost-effective and safe, and is seen to have a promising role in cancer treatment.
Controversy
A motif found throughout the history of cancer therapy is the tendency for overtreatment. From the time of its inception, the use of adjuvant therapy has received scrutiny for its adverse effects on the quality of life of cancer patients. For example, because side effects of adjuvant chemotherapy can range from nausea to loss of fertility, physicians regularly practice caution when prescribing chemotherapy.In the context of melanoma, certain treatments, such as Ipilimumab, result in high grade adverse events, or immune-related adverse events, in 10-15% of patients that parallel the effects of metastatic melanoma itself. Similarly, several common adjuvant therapies are noted for having the potential of causing cardiovascular disease. In such cases, physicians must weigh the cost of recurrence against more immediate consequences and consider factors, like age and relative cardiovascular health of a patient, before prescribing certain types of adjuvant therapy.
One of the most notable side effects of adjuvant therapy is the loss of fertility. For pre-pubescent males, testicular tissue cryopreservation is an option for preserving future fertility. For post-pubescent males, this side effect can be assuaged through semen cryopreservation. For pre-menopausal females, options to preserve fertility are oftentimes much more complex. For example, breast cancer patients of fertile age oftentimes have to weigh the risks and benefits associated with starting an adjuvant therapy regimen after primary treatment. In the some low-risk, low-benefit situations, forgoing adjuvant treatment altogether can be a reasonable decision, but in cases where the risk of metastasis is high, patients may be forced to make a difficult decision. Though options for fertility preservation exist, they are more often than not time-consuming and costly.
As a result of complications that can stem from liberal use of adjuvant therapy, the philosophy surrounding the use of adjuvant therapy in the clinical setting has shifted towards the goal of doing as little harm as possible to patients. The standards for dose intensity of adjuvant treatments and treatment duration are regularly updated to optimize regimen efficiency while minimizing toxic side effects that patients must shoulder.
Concomitant or concurrent systemic cancer therapy
Concomitant or concurrent systemic cancer therapy refers to administering medical treatments at the same time as other therapies, such as radiation. Adjuvant hormonal therapy is given after prostate removal in prostate cancer, but there are concerns that the side effects, in particular the cardiovascular ones, may outweigh the risk of recurrence. In breast cancer, adjuvant therapy may consist of chemotherapy and radiotherapy, especially after lumpectomy, and hormonal therapy. Adjuvant therapy in breast cancer is used in stage one and two breast cancer following lumpectomy, and in stage three breast cancer due to lymph node involvement.In glioblastoma multiforme, adjuvant chemoradiotherapy is critical in the case of a completely removed tumor, as with no other therapy, recurrence occurs in 1–3 months.
In early stage one small cell lung carcinoma, adjuvant chemotherapy with gemcitabine, cisplatin, paclitaxel, docetaxel, and other chemotherapeutic agents, and adjuvant radiotherapy is administered to either the lung, to prevent a local recurrence, or the brain to prevent metastases.
In testicular cancer, adjuvant either radiotherapy or chemotherapy may be used following orchidectomy. Previously, mainly radiotherapy was used, as a full course of cytotoxic chemotherapy produced far more side effects then a course of external beam radiotherapy. However, it has been found a single dose of carboplatin is as effective as EBRT in stage II testicular cancer, with only mild side effects is technically adjuvant, and most experts agree that cranial irradiation decreases risk of central nervous system relapse in ALL and possibly acute myeloid leukemia, but it can cause severe side effects, and adjuvant intrathecal methotrexate and hydrocortisone may be just as effective as cranial irradiation, without severe late effects, such as developmental disability, dementia, and increased risk for second malignancy.