Doctors use chemotherapy either as a first-line therapy or in combination with other treatments, such as surgery. If chemotherapy does not work, a person may need to consider other treatment options.

Signs that cancer is not responding to chemotherapy include:

  • tumor not shrinking
  • tumor growing
  • cancer spreading from its original site to other areas of the body, which is called metastasis
  • cancer symptoms returning
  • additional symptoms appearing

Depending on the type and stage of cancer, second-line or third-line treatment options may be available.

In this article, we explain some of the alternative cancer treatment options if chemotherapy is not working. Below is a list of scientifically proven cancer treatments that can serve as either complementary or primary treatments.

Radiation therapy

doctor speaking to patient
Alternative treatments may be available if chemotherapy is not working.

Radiation therapy uses radiation to kill cancer cells and reduce the size of tumors.

Radiation therapy can serve as a primary treatment, but it also works well with other treatments, such as surgery.

Radiation therapy damages the DNA in cancer cells to the extent that they can no longer repair themselves.

These damaged cancer cells will stop dividing and eventually die, at which point the body will break them down and remove them.

There are two different types of radiation therapy, which are called external beam radiation therapy and internal beam radiation therapy.

External beam radiation therapy is a local treatment, which means that it targets a specific part of the body.

This form of radiation therapy uses a large machine that sends radiation from several directions to the required area.

Internal beam radiation therapy uses a radiation source that doctors implant inside the body near the tumor. It affects a smaller area of the body than external radiation therapy.

The implants that doctors use in this therapy can be either permanent or temporary. Temporary implant removal usually occurs after a few minutes or days. People with temporary implants are radioactive until the removal of the implant, while permanent implants gradually stop giving off radiation over time.

Advantages of radiation therapy

Radiation therapy has several advantages, including:

  • causes only moderate pain
  • minimal or no hair loss
  • effectively kills large numbers of cancer cells within a tumor
  • relatively safe for the individual as the radiation specifically targets the tumor
  • minimal damage to organs near the tumor

However, it is important to note that the intensity of pain will differ from person to person, and the damage to organs will vary depending on their location in relation to the tumor.

Disadvantages of radiation therapy

There are also several disadvantages of radiation therapy, such as:

  • people who receive internal beam radiation therapy will be radioactive for a short period
  • potential damage to vital organs if they are particularly close to the tumor
  • may not kill all cancer cells if the tumor is very large
  • inconvenient and time-consuming as people require treatment on 5 days of the week, and it can last for up to 2 months
  • expensive, although the exact cost depends on the type and amount of treatment
  • skin redness or soreness around the site of radiation
  • site-specific side effects — for example, treating cancer in the esophagus or gastrointestinal tract can cause nausea or vomiting


Some types of cancer do not respond well to radiation or chemotherapy, so a person may need to try immunotherapy.

Immunotherapy aims to help the immune system fight cancer in the same way that it fights infections and foreign pathogens.

Immunotherapies either stimulate the immune system in a general way or train it to attack cancer cells directly.

The main methods of delivering immunotherapy include:

  • Monoclonal antibodies: With this method, a person receives synthetic antibodies that bind to specific proteins on cancer cells. This binding marks the cancer cell to help the immune system locate and destroy it.
  • Checkpoint inhibitors: These are medications that stimulate T cells, which then identify and attack cancer cells more efficiently.
  • Cancer vaccines: Vaccines stimulate the immune system to fight cancer. Some vaccines, such as the human papillomavirus (HPV) vaccine, can have protective effects. Specific types of HPV are known to cause certain cancers.
  • Adoptive cell transfer: This involves removing T cells from a tumor and modifying them in a laboratory. After about 2 to 8 weeks, doctors return the T cells to the body. The aim is to boost the ability of the T cells to detect and destroy cancer cells.

Advantages of immunotherapy

Immunotherapy may work when other treatments do not. Its other potential advantages include:

  • effective against many types of cancer
  • can improve the success of other treatments
  • causes fewer side effects than treatments that target all the cells in the body, such as chemotherapy
  • after learning to target cancer cells, the immune system remembers this response if cancer reappears

Disadvantages of immunotherapy

The disadvantages of this form of treatment include:

  • risk of overstimulating the immune system and causing it to attack healthy organs, which can lead to severe complications in the lungs, intestines, kidneys, or other organs
  • side effects, such as fatigue, cough, nausea, loss of appetite, skin rash, and flu-like symptoms

Hormone therapy

woman standing on scales
Females may gain weight with hormone therapy.

Hormone therapy can treat some types of cancer, including prostate cancer and breast cancer, by taking advantage of the disease’s dependence on hormones to grow.

Hormone therapy works by either stopping the body from producing hormones or interfering with how hormones affect the body.

Hormone therapy to treat breast cancer, or anti-estrogen therapy, focuses on lowering estrogen levels.

The treatment may involve surgical procedures, such as removal of the ovaries, or medications that interrupt signals from the pituitary gland, a gland that stimulates estrogen production.

Hormone therapy to treat prostate cancer, or androgen-suppression therapy, lowers testosterone and dihydrotestosterone (DHT) production. Treatments include surgical procedures to remove one or both testicles and medications that prevent the production of testosterone and DHT.

Advantages of hormone therapy

Advantages of hormone therapy include:

  • effective treatment for preventing the spread of cancer to other parts of the body
  • can help reduce the risk of cancer returning after surgery

Disadvantages of hormone therapy

There are some disadvantages to this type of treatment, such as:

  • only works on cancers that require hormones to grow
  • side effects for females include headaches, hot flashes, weight gain, and vaginal dryness
  • side effects for males include fatigue, hot flashes, breast sensitivity or enlargement, nausea, impotence, and lower sexual desire

Targeted therapy

Targeted therapy uses medication that specifically targets cancer cells, destroying them from the inside.

Unlike chemotherapy, these medications do not affect healthy cells because they identify particular genetic abnormalities in cancer cells. Targeted therapy works best in combination with other treatments.

There are many types of targeted therapy, and they employ different methods to fight cancer.

Targeted therapies may fight cancer by:

  • blocking or turning off chemical signals that stimulate cancer cell growth
  • changing proteins inside cancer cells, causing cell death
  • preventing cancer cells from stimulating the growth of new blood vessels
  • triggering an immune response to destroy cancer cells
  • delivering toxic substances to cancer cells to kill them without affecting other cells

Advantages of targeted therapy

Targeted therapy may be beneficial due to the advantages that it offers:

  • specifically targets cancer cells
  • not toxic to healthy cells
  • the wide array of treatment options makes individual treatment plans possible

Disadvantages of targeted therapy

The disadvantages of targeted therapy include:

  • only works for tumors with specific genetic mutations
  • cancer cells may develop resistance
  • side effects include diarrhea, skin rash, issues with blood clotting, high blood pressure, and liver problems, such as hepatitis

Making a decision

senior man taking medication
Other health problems may influence treatment options.

If chemotherapy does not work or stops working, there may be other treatment options available.

The likelihood of this depends on the type and stage of cancer and whether or not the person has other health problems.

If chemotherapy stops working for someone, they will need to speak with their cancer doctor, or oncologist, about other potential treatment options.

Factors to keep in mind and discuss with an oncologist include:

  • how well and for how long the first-line treatment was working
  • the current status of the cancer
  • how a new treatment will affect the overall prognosis
  • if the cancer has spread
  • the success rate of any available alternative treatments
  • the possible side effects of other treatment options


Alternative treatment options may be available if chemotherapy does not work for a person. However, the likelihood of eradicating cancer from the body declines with successive treatments.

The average life expectancy for people who receive second- and third-line treatments varies according to a number of factors. For example, a literature review shows a wide range in the life expectancy of people who received second-line treatments for non-small cell lung cancer.

Unfortunately, it is difficult to give a definitive answer regarding a person’s likely outlook.


There are usually alternative treatments available if chemotherapy does not work. However, this may depend on the type of cancer and other factors.

After considering alternative treatment options, some people choose to decline further treatment. If this is the case, an oncologist will focus on improving the individual’s quality of life by developing a treatment plan to manage their cancer symptoms.

If chemotherapy treatment stops working, the person should discuss their options with their oncologist, members of their treatment team, and their family members before making a decision on their treatment going forward.