How Salvage Therapy Works

Treating HIV and Cancer When Other Options Fail

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Salvage therapy is treatment used when a disease does not respond to all other standard treatments tried. Salvage therapy is most often associated with HIV (human immunodeficiency virus) and cancer and suggests that your treatment options are limited.

Even so, the term is not clearly defined and doesn't mean that a person is at the end stage of their illness. Salvage therapy can take many forms, including a more expansive combination of standard therapies, clinical trials, and experimental drugs.

Black doctor holding pills with patient

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Salvage therapies tend to be more aggressive than standard therapies and cause more side effects, but this is not always the case. The definition of salvage therapy is always evolving as new drugs and treatments are introduced.

This article will discuss salvage therapy, how it is used in HIV and cancer, its side effects, the challenges you may face in coping during salvage therapy, and what may happen after treatment.

What Is Salvage Therapy?

Salvage therapy is not a specific treatment. It means that a person has been treated in line with standard protocols—from first-line therapy to second-line therapy to third-line therapy, and so on—but those treatments have proven ineffective or intolerable. It essentially means that standard treatment options have been exhausted.

However, salvage therapy does not always indicate that there is no hope. It is not the same thing as hospice care (comfort care for people with a terminal illnesses) or palliative care (treating symptoms to reduce suffering in people with cancer and other diseases).

Salvage therapy simply implies that a doctor wants to continue treatment in order to stabilize a disease, stop it from progressing, and improve or prevent symptoms. Salvage therapy generally implies that the treatment is not curative, although, in some cases, salvage therapy can lead to cancer remission (when symptoms are reduced or go away).

Because the term "salvage therapy" has negative connotations and can cause people distress, doctors will often refer to this stage of treatment as "rescue therapy."

Recap

Salvage therapy is used when all standard treatments have failed. It usually involves a combination of treatments designed to stabilize a disease and prevent it from progressing.

Conditions

Salvage therapy is structured and follows guidelines based on available scientific research. It may extend into clinical trials or involve experimental drugs, but, even then, treatment decisions are based on the best available evidence.

Salvage therapies are commonly used in people with advanced HIV infection or advanced cancer, but there are other situations in which salvage therapy may be applied.

HIV

Salvage therapy is used in people with HIV who no longer respond to standard antiretroviral therapies. HIV is a chronic infection treated with different combinations of antiretroviral drugs that, together, prevent the virus from replicating and the disease from progressing.

Over time, HIV can gradually develop resistance to the drugs, making them less effective. If the treatment fails, another combination can be prescribed to put the virus back in check. Ideally, if treated properly, a person living with HIV will have plenty of treatment options available to them to last a lifetime.

However, this is not always the case. Drug resistance can develop rapidly if a person interrupts treatment or frequently skips doses. When this happens, not only will the current drugs be less effective, but so too will other drugs of the same class.

Resistance can also be transmitted, meaning that you can pick up a drug-resistant virus during sex or from other modes of transmission.

Salvage therapy may also be required if certain medications are intolerable and severely limit your treatment options.

When Salvage Therapy Is Used

Salvage therapy is typically tried when there is high-level, multidrug resistance. This is determined with genetic resistance testing, which identifies drug-resistant viral mutations, and phenotypic testing, which exposes the virus to all available antiretroviral drugs.

Based on the findings, your healthcare provider will prescribe the combination of drugs that the virus is most responsive to. While standard therapies involve as few as two antiretroviral drugs, salvage therapies may contain four, five, or more drugs. Because of this, side effects are more likely, and dosing schedules may be far more complicated.

Even so, when prescribed rationally, salvage therapy can help a person achieve and maintain full viral suppression, stopping disease progression and allowing the immune system to rebuild itself.

Changing Definitions

The definition of salvage therapy is constantly changing. In the past, salvage therapy and third-line therapy were considered synonymous because there were fewer drug options. Today, there are not only more options, but many of the newer antiretrovirals are less prone to resistance, even in people with a history of treatment failures.

By way of example, people on salvage therapy in the late-1990s were given a new lease with the introduction of Viread (tenofovir) in 2001. The novel HIV drug was able to overcome deep resistance in people who had been on treatment for decades.

Recap

Salvage therapy is typically used in people with HIV who have high-level, multidrug resistance. This is often due to not adhering to treatment schedules or dosing, during which time the virus can mutate and become resistant to the drug.

Cancer

The National Cancer Institute defines salvage therapy as "treatment that is given after the cancer has not responded to other treatments."

Salvage therapy can take many forms. Depending on the type of cancer a person has, this may include:

  • Chemotherapy (drugs are used to kill fast-growing cells)
  • Radiation therapy (high-energy waves are used to kill tissues)
  • Immunotherapy (uses your immune system to fight cancer)
  • Targeted therapies (drugs that target specific types of cancer cells)
  • Hormone therapy (prevents hormones from binding on certain types of cancer cells)
  • Surgery (tumor removal or repair of affected tissues)
  • Palliative care (treatments aimed to reduce symptoms)

Clinical trials may also be involved.

When Salvage Therapy Is Used

Salvage therapy is commonly used in people whose cancer fails to respond to standard treatments, referred to as refractory or treatment-resistant cancer. It may also be considered when there is cancer recurrence (also known as a relapse).

The first-line treatment for most types of cancer is chemotherapy ("chemo"). The choice of chemo tends to follow standard guidelines based on the type, stage, and grade of cancer and other factors. Salvage therapy may be used when a person has not responded to a first-line therapy.

There is not one fixed salvage therapy for cancer. It can differ by the cancer type and other factors, including a person's genetics, age, and performance status. There may also be first-, second-, and even third-line salvage therapies for cancers. With every subsequent treatment, the response (reducing the tumor or improving survival) tends to be less.

Salvage therapy may have a slightly different meaning for people whose cancer can’t be cured. For these individuals, the goal of therapy is to keep the disease from progressing and avoid further illness. As such, there may be first-line, second-line, and subsequent protocols in place before a treatment is finally considered salvage therapy.

Does Salvage Mean Incurable?

Salvage therapy may seem to suggest that cancer is inherently untreatable or incurable, but that's not necessarily the case.

People with prostate cancer recurrence have achieved remission with salvage therapies involving prostatectomy (prostate removal), brachytherapy (a type of targeted radiation), and high-intensity ultrasound. Similarly, studies have shown that up to 14% of people on salvage therapy for acute myeloid leukemia (AML) achieve remission.

Recap

Salvage therapy may be used in people whose cancer is refractory (treatment resistant) or who have experienced recurrence (relapse).

Other Conditions

Salvage therapies can be applied to other diseases in which treatment options are limited and standard treatments have failed to slow the progression of a disease. Some of these may be desperate measures in which the potential benefits are seen to outweigh the risks.

Examples include:

Side Effects

Salvage therapy is presumed to cause more side effects of traditional therapies because more treatments are involved. But this is not always the case. Moreover, the consequences of not treating diseases like HIV and cancer can be more serious than the side effects of treatment.

Ultimately, how well the patient handles the adverse effects of the treatment (the tolerability) will factor into the clinical decisions as much as the effectiveness of treatment.

HIV

When prescribing salvage therapy for HIV, doctors will perform the same tests and procedures used for every other stage of treatment. This includes reviewing your medical history to identify your risk of certain side effects.

Blood tests such as liver functions tests and kidney function tests can help avoid drug toxicity by ensuring the organs are working properly. Even so, side effects can occur, particularly if drugs from the same class are used.

Possible side effects include:

  • Dizziness
  • Fatigue
  • Headache
  • Stomach upset
  • Nausea or vomiting
  • Sleep disturbances
  • Vivid dreams
  • Rash
  • Reduced urine output
  • Frequent urination
  • Peripheral neuropathy (pins-and-needles sensations)
  • Jaundice (yellowing of the skin and eyes)
  • Lipodystrophy (body fat redistribution)

Cancer

As with HIV, cancer treatment is carefully considered to ensure that the benefits outweigh the risks. Even so, second- and third-line chemotherapies tend to involve more drugs than first-line chemotherapy and cause more side effects. Add to this the impact of radiation and hormonal therapies, and the side effects can be significant.

To reduce the impact of treatment, palliative care may be started to better manage side effects and improve the quality of life. This is an option whether the cancer is curable or incurable.

Possible side effects of salvage therapy include:

Recap

Salvage therapies may cause more side effects because more treatments are involved, but it's not always the case. When choosing a therapy, doctors will consider both its effectiveness and tolerability.

How to Cope

Salvage therapy is generally an indication that your immune system is in a weakened state. When you are immunosuppressed or immunocompromised, your body is less able to fight infection.

In people with HIV, this low immune state is the result of the virus, which depletes immune cells. In people with cancer, both the tumor and cancer treatment contribute.

To prevent infection while on salvage therapy, speak with your doctor about the different vaccines you need, including flu and COVID-19 vaccines. Use standard precautions to avoid contagions, including frequent handwashing, avoiding crowds, and wearing face masks.

You also need to do your part to keep yourself healthy. This includes eating a healthy diet, quitting cigarettes, and exercising within reason. Your doctor can offer guidance or refer you to a nutritionist, physical therapist, or personal trainer when appropriate.

Learning that you need salvage therapy can be stressful, leading to poor sleep, irritability, loss of concentration, and depression. To avoid this, ask your doctor for a referral to an HIV or cancer support group or seek one-on-one care from a therapist or psychiatrist. Stress management techniques, along with ample sleep and the avoidance of alcohol, can also help.

After Salvage Therapy

After salvage therapy has been prescribed, the single most important thing you can do is to see your doctor regularly. Because salvage therapy poses a risk of toxicity, regular blood tests may be needed to proactively identify liver or kidney problems before they turn severe.

At the same time, the doctor will want to evaluate your response to treatment. With HIV, this would involve a viral load test (concentration of the virus in the blood) to see how well the drugs are working.

For cancer, this may involve blood tests to check for tumor markers (substances released by cancer cells or produced by the body in reaction to a tumor) and imaging studies to check the size of the tumor.

When first starting salvage therapy, you may be asked to be seen more frequently than usual. Even if you achieve the optimal response—such as an undetectable viral load or cancer remission—you would still need to see your doctor regularly to monitor your condition.

Summary

Salvage therapy refers to treatments used after a condition has not responded to the usual treatments. It is most often used in treating HIV or cancer. Salvage therapy tends to be more aggressive than standard treatments and may produce side effects. If one form of salvage therapy is not effective, another may be used.

A Word From Verywell

As scary as salvage therapy may sound—suggesting your good health is being "salvaged"—don't assume that you are at the end of the line as far as treatment options are concerned. Salvage therapy aims to continue treatment to stabilize your condition and ideally improve it.

If faced with salvage therapy, ask your doctor as many questions as needed to understand what is involved and the likely prognosis. If you can't, bring a friend, family member, or patient advocate with you to your appointment. Asking the right questions not only reduces the fear of the unknown but also helps you make informed choices.

Frequently Asked Questions

  • What is the difference between adjuvant and salvage radiation therapy?

    Adjuvant radiation therapy is using high-powered radiation beams to kill remaining cancer cells after your initial therapy, such as chemo or surgery, is used. On the other hand, salvage radiation therapy is given when cancer recurrence is confirmed or suspected.

  • What happens if salvage therapy doesn’t work?

    Salvage therapy may sound like your treatment options are exhausted, but there may be more than one therapy still available for you to try. If one fails, there may be another. Clinical trials can also be explored as part of salvage therapy if other options have been exhausted.

  • Are there other treatments to do during salvage therapy?

    Your immune system may be compromised during salvage therapy, making you vulnerable to infection. In such cases, prophylactic (disease-preventing) drugs may be prescribed to reduce your risk of opportunistic infections (infections that occur more often in people with weakened immune systems) or increase the number of infection-fighting white blood cells in your body.

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