Adjuvant Therapy

Adjuvant therapy (????? ????????), also known as an adjunct therapy, add-on therapy, and adjuvant care, 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 the known disease is left behind following surgery, then further treatment is not technically adjuvant. Siddha Spirituality of Swami Hardas Life System appeals to our valuable readers to know about adjuvant therapy, definition, meaning, neoadjuvant therapy for specific cancers, and side effects.

Adjuvant therapy Definition (????? ???????? ???????)

Treatment that is given in addition to the primary (initial) treatment. Adjuvant treatment is an addition designed to help reach the ultimate goal. Adjuvant therapy for cancer usually refers to surgery followed by chemo- or radiotherapy to help decrease the risk of cancer recurring (coming back). In Latin “adjuvans” means to help and, particularly, to help reach a goal.

Adjuvant therapy Meaning (????? ???????? ????)

It is often used after primary treatments, such as surgery, to lessen the chance of your cancer coming back. Even if your surgery was successful at removing all visible cancer, microscopic bits of cancer sometimes remain and are undetectable with current methods. Adjuvant therapy given before the main treatment is called neoadjuvant therapy. This type of adjuvant therapy can also decrease the chance of cancer coming back, and it’s often used to make the primary treatment — such as an operation or radiation treatment — easier or more effective.

Neoadjuvant therapy (???????? ????????)

Neoadjuvant therapy, in contrast to adjuvant therapy, is given before the main treatment. For example, systemic therapy for breast cancer that is given before the 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. 

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 specific adjuvant therapy. The aim of adjuvant treatment is to improve disease-specific symptoms and overall survival. Because the treatment is essential for 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 many types of cancer, including:

• Colon cancer
• Lung cancer
• Pancreatic cancer
• Breast cancer
• Prostate cancer
• Some gynecological cancers

Some forms of cancer fail to benefit from adjuvant therapy, however. Such cancers include renal cell carcinoma and certain forms of brain cancer.

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 the side effects of adjuvant chemotherapy can range from nausea to loss of fertility, physicians regularly practice caution when prescribing chemotherapy.

Similarly, several common adjuvant therapies are noted for having the potential of causing cardiovascular disease. In such cases, physicians must weigh the cost of future recurrence against more immediate consequences and consider factors, like age and relative cardiovascular health of a patient, before prescribing certain types of adjuvant therapy.

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
• 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.

Dose-Dense Chemotherapy (???-???? ??????????)

Dose-dense chemotherapy (DDC) has recently emerged as an effective method of adjuvant chemotherapy administration. DDC uses the Gompertz curve to explain tumor cell growth after initial surgery removes most of the tumor mass.

Cancer cells that are left over after surgery are typically rapidly dividing cells, leaving them the most vulnerable to chemotherapy.

Standard chemotherapy regimens are usually administered every 3 weeks to allow normal cells time to recover. 

 

Adjuvant therapy for Specific cancers (??????? ????? ?? ??? ????? ????????)

Malignant melanoma (???? ????????)

The role of adjuvant therapy in malignant melanoma is and has been hotly debated by oncologists. In 1995 a multicenter study reported improved long-term and disease-free survival in melanoma patients using interferon-alpha 2b as adjuvant therapy. Thus, later that year the U.S. Food and Drug Administration (FDA) approved interferon alpha 2b for melanoma patients who are currently free of disease, to reduce the risk of recurrence.

Multiple studies have shown that adjuvant radiotherapy improves local recurrence rates in high-risk melanoma patients. The studies include at least two M.D. Anderson cancer center studies. However, none of the studies showed that adjuvant radiotherapy had a statistically significant survival benefit.

A number of studies are currently underway to determine whether immunomodulatory agents which have proven effective in the metastatic setting are of benefit as adjuvant therapy for patients with resected stage 3 or 4 diseases.

Colorectal cancer (?????????? ?????)

Adjuvant chemotherapy is effective in preventing the outgrowth of micrometastatic disease from colorectal cancer that has been removed surgically. Studies have shown that fluorouracil is effective adjuvant chemotherapy among patients with microsatellite stability or low-frequency microsatellite instability, but not in patients with high-frequency microsatellite instability.

Pancreatic cancer (??????? ?? ?????)

Exocrine pancreatic cancer has one of the lowest 5-year survival rates out of all cancers. Because of the poor outcomes associated with surgery alone, the role of adjuvant therapy has been extensively evaluated. A series of studies have established that 6 months of chemotherapy with either gemcitabine or fluorouracil, as compared with observation, improves overall survival. 

Lung Cancer (??????? ?? ?????)

In 2015, a comprehensive meta-analysis of 47 trials and 11,107 patients revealed that NSCLC patients benefit from adjuvant therapy in the form of chemotherapy and/or radiotherapy. The results found that patients given chemotherapy after the initial surgery lived 4% longer than those who did not receive chemotherapy. The toxicity resulting from adjuvant chemotherapy was believed to be manageable.

Bladder cancer (???????? ?? ?????)

Neoadjuvant platinum-based chemotherapy has been demonstrated to improve overall survival in advanced bladder cancer, but there exists some controversy in the administration. The unpredictable patient response remains the drawback of neoadjuvant therapy. 

Breast cancer (???? ?????)

It has been known for at least 30 years that adjuvant chemotherapy increases the relapse-free survival rate for patients with breast cancer In 2001 after a national consensus conference, a US National Institute of Health panel concluded: “Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status.”

Agents used include:

• Cyclophosphamide
• Methotrexate
• Fluorouracil
• Doxorubicin
• Docetaxel
• Paclitaxel
• Epirubicin

However, ethical concerns have been raised about the magnitude of the benefit of this therapy since it involves further treatment of patients without knowing the possibility of relapse. 

Combination adjuvant chemotherapy for breast cancer (???? ????? ?? ??? ?????? ????? ??????????)

Giving two or more chemotherapeutic agents at once may decrease the chances of recurrence of cancer, and increase overall survival in patients with breast cancer. Commonly used combination chemotherapy regimens used include:

• Doxorubicin and cyclophosphamide
• Doxorubicin and cyclophosphamide followed by docetaxel
• Cyclophosphamide, methotrexate, and fluorouracil
• Docetaxel and cyclophosphamide
• Docetaxel,[doxorubicin, and cyclophosphamide
• Cyclophosphamide, epirubicin, and fluorouracil

Ovarian Cancer (??????????? ?? ?????)

Roughly 15% of ovarian cancers are detected at the early stage, at which the 5-year survival rate is 92%. A Norwegian meta-analysis of 22 randomized studies involving early-stage ovarian cancer revealed the likelihood that 8 out of 10 women treated with cisplatin after the initial surgery were overtreated.

Most cases of ovarian cancers are detected at the advanced stages when survival is greatly reduced.

Cervical cancer (?????? ?????)

In early-stage cervical cancers, research suggests that adjuvant platinum-based chemotherapy after chemo-radiation may improve survival. For advanced cervical cancers, further research is needed to determine the efficacy, toxicity, and effect on the quality of life of adjuvant chemotherapy.

Endometrial cancer (??????????????? ?????)

Since most early-stage endometrial cancer cases are diagnosed early and are typically very curable with surgery, adjuvant therapy is only given after surveillance and histological factors determine that a patient is at high risk for recurrence. Adjuvant pelvic radiation therapy has received scrutiny for its use in women under 60, as studies have indicated decreased survival and increased risk of second malignancies following treatment.

In advanced-stage endometrial cancer, adjuvant therapy is typically radiation, chemotherapy, or a combination of the two. While advanced-stage cancer makes up only about 15% of diagnoses, it accounts for 50% of deaths from endometrial cancer. Patients who undergo radiation and/or chemotherapy treatment will sometimes experience modest benefits before relapse.

Testicular cancer (???? ?????)

Stage I

For seminoma, the three standard options are:

• Active surveillance
• Adjuvant radiotherapy, or adjuvant chemotherapy

For non-seminoma, the options include:

• Active surveillance
• Adjuvant chemotherapy
• Retroperitoneal lymph node dissection

As is the case for all reproductive cancers, a degree of caution is taken when deciding to use adjuvant therapy to treat early-stage testicular cancer. Though the 5-year survival rates for stage I testicular cancers is approximately 99%, there still exists controversy over whether to overtreat stage I patients to prevent relapse or to wait until patients experience a relapse.

Patients treated with standard chemotherapy regimens can experience:

• Second malignant neoplasms
• cardiovascular disease
• Neurotoxicity
• Nephrotoxicity
• Pulmonary toxicity
• Hypogonadism
• Decreased fertility
• Psychosocial problems

As such to minimize overtreatment and avoid potential long-term toxicity caused by adjuvant therapy, most patients today are treated with active surveillance.

Adjuvant therapy Side effects (????? ???????? ??????????)

Depending on what form of treatment is used, adjuvant therapy can have side effects, like all therapy for neoplasms. Chemotherapy frequently causes vomiting, nausea, alopecia, mucositis, myelosuppression particularly neutropenia, sometimes resulting in septicemia.

Some chemotherapeutic agents can cause acute myeloid leukemia, in particular, the alkylating agents. Rarely, this risk may outweigh the risk of recurrence of the primary tumor.

Depending on the agents used, side effects such as:

• Chemotherapy-induced peripheral neuropathy
• Leukoencephalopathy
• Bladder damage
• Constipation or diarrhea
• Hemorrhage
• Post-chemotherapy cognitive impairment

Radiotherapy causes radiation dermatitis and fatigue, and, depending on the area being irradiated, may have other side effects. For instance, radiotherapy to the brain can cause memory loss, headache, alopecia, and radiation necrosis of the brain.

If the abdomen or spine is irradiated, nausea, vomiting, diarrhea, and dysphagia can occur. If the pelvis is irradiated, prostatitis, proctitis, dysuria, metritis, diarrhea, and abdominal pain can occur.

Adjuvant hormonal therapy for prostate cancer may cause cardiovascular disease, and other, possibly severe, side effects.

Reference:

• https://en.wikipedia.org/wiki/Adjuvant_therapy
• https://www.medicinenet.com/script/main/art.asp?articlekey=2151
• https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/adjuvant-therapy/art-20046687