What Is Combination Chemotherapy?

Benefits and risks of combining chemotherapy and/or immunotherapy drugs

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Combination chemotherapy refers simply to the use of more than one chemotherapy medication at a time to treat cancer. In the past, cancer was often treated with a single drug, but current treatments for many types of cancer use a combination of two or more different drugs simultaneously. Since chemotherapy drugs affect cancer cells at different points in the cell cycle, using a combination of drugs increases the chance that all of the cancer cells will be eliminated. At the same time, however, using more than one drug has the disadvantage of increasing the risk of drug interactions, and if there is a problem, it may be hard to know which drug was at fault.

Recently, chemotherapy has also been used with a type of immunotherapy known as checkpoint inhibition, and may increase the chance that the immunotherapy drugs will be effective. What should you know before you begin combination chemotherapy?

Woman hooked up to IV

History of Combination Chemotherapy

The use of combination chemotherapy to treat cancer was inspired in the 1960s when scientists wondered whether the approach to treating tuberculosis—using a combination of antibiotics to reduce the risk of resistance—would work for the treatment of cancer as well. Using this approach, cancers that had previously been almost universally fatal such as acute lymphocytic leukemia and Hodgkin’s lymphoma became largely curable. Since that time, combination chemotherapy has been adopted for the treatment of many other cancers as well.

In the 1970's, combination chemotherapy was found to be more effective than single drugs for people with lung cancer, and more effective than "sequential chemotherapy" or using chemotherapy drugs one at a time in sequence, rather than at the same time.

It's only in the last decade that chemotherapy has been added to a new type of immunotherapy called checkpoint inhibition. In some situations, adding chemotherapy drugs appears to make the immunotherapy drugs more effective.

At the current time, combination chemotherapy may be more appropriate in some situations and with some cancers, while single-drug chemotherapy may better in others.


There are many combinations of chemotherapy drugs that are used for different types of cancer.

Solid tumors

Combination chemotherapy is used with several types of solid tumors. An example with lung cancer is using the combination of Platinol (cisplatin) and Navelbine (vinorelbine) to treat non-small cell lung cancer. For women who have early stage lung cancer, combining two drugs (often Adriamycin and Cytoxan), followed later by Taxol appears to reduce the risk of recurrence.

Leukemias and Lymphomas

With some leukemias and Hodgkin lymphoma, several chemotherapy drugs may be used together, and combination chemotherapy has greatly increased survival rates from many of these diseases.

Sometimes an acronym is used to describe combination chemotherapy. One example is ABVD for Hodgkin's disease which stands for the combination of the chemotherapy medications Adriamycin (doxorubicin), Blenoxane (bleomycin), Oncovin (vinblastine) and DTIC-Dome (dacarbazine).

Combination Chemotherapy and Immunotherapy Drugs

When chemotherapy is used along with immunotherapy, benefits may go beyond using the combination of drugs. Immunotherapy drugs work simplistically by helping the immune system recognize and attack cancer cells.

When cancer cells are broken down by chemotherapy drugs, it can help the immune system recognize these cells as abnormal so that the immunotherapy drugs can be more effective. This phenomena, known as the abscopal effect, is also sometimes seen when radiation therapy is combined with the type of immunotherapy known as checkpoint inhibitors.


There are several theoretical advantages to using a combination of chemotherapy medications rather than single agents alone. Some of these include:

Decreasing Resistance

Using a combination of drugs may decrease the chance that a tumor will be resistant to the treatment. Just as a combination of antibiotics may be used in case a particular bacteria is resistant to one of the medications, using two or more chemotherapy drugs reduces the risk that a tumor will be resistant to the treatment. It is usually the development of resistance that results in chemotherapy becoming ineffective over time.

Early Administration of Both (or More Than Two) Drugs

Using more than one drug at a time can make it possible to give all medications as early as possible in the disease rather than waiting.

Hitting Cancer in More Than One Place

Using more than one drug at a time makes it possible to target several processes in a cancer's growth at the same time. Cancer is a complex disease involving many steps. The use of chemotherapy medications that work on different molecular targets, or points in the cancer process should, in theory, raise the chances of eliminating the cancer.       

Addressing Tumor Heterogeneity                                                

Scientists use the term "tumor heterogeneity" to describe how the cancer cells in tumors vary from each other. While the initial cells in a cancer are "clones"—in other words identical—successive divisions result in changes in the cells. Some of the resulting cells in a tumor may respond to a particular drug while others may be more responsive to another drug. This is easier to understand by realizing that cells in one part of a tumor may be very different from cells in a metastasis or even a different part of the same tumor. As cancer cells continue to divide, they develop successively more mutations, mutations that can sometimes make one drug ineffective while another may still be effective.

Opportunity to Use a Lower Dosage of One or Both Drugs.

Recently research is also looking at ways in which using a combination of chemotherapy medications can be used to allow oncologists to use some of the drugs at lower doses, and hence reduce the likelihood of toxic effects. In other words, instead of using a high dose of one drug, it may be possible to use lower doses of two or more drugs.


Some drugs may do more than work at different places in to bring about an additive effect in treatment, but can instead be synergistic; the effect that occurs from the combination of drugs is greater than if you were to add the individual effects of each of the drugs together.

In practice, the use of combination chemotherapy with many cancers has either been found to improve survival, or result in a better response to treatment. This is especially true when chemotherapy is used as an adjuvant treatment, that is, treatment designed to get rid of any remaining cells that are left after surgery or other therapies (such as the chemotherapy often given after surgery for early stage breast cancer). With metastatic cancer, the goal of treatment is often different. For example, with metastatic breast cancer, since it is no longer curable, the goal is to use the least amount of treatment possible to control the disease. In this case, a single chemotherapy drug may be preferable and allow for a better quality of life.

Disadvantages and Risks

Some possible disadvantages of combination chemotherapy regimens include:

More Side Effects

An increased likelihood of chemotherapy side effects is common when more than one drug is used. It goes without saying that any time more medications are used it is more likely that side effects will occur. There are exceptions to this general rule, however, even if the combination does not allow for lower doses to be used. An example is the combination of a BRAF inhibitor and a MET inhibitor in melanoma (and some other cancers) in which the combination of the two drugs actually causes fewer side effects than either drug alone.

Difficulty Figuring Out the Source of Side Effects

If a person develops a side effect when several medications are used, it may be difficult to know which of the medications is responsible. In this case, all of the medications may need to be discontinued if the side effect is serious.

Drug Interactions

Sometimes side effects occur not due to a particular medication, but due to reactions between the medications. The more medications a person is using (both chemotherapy drugs and other medications), the greater the chance that an interaction will occur.

Accumulation of Side Effects

When more than one drug is used, side effects present with both drugs may add together. For example, if you use two drugs that cause a low white blood cell count, the risk of chemotherapy-induced neutropenia (a reduced number of the type of white blood cells known as neutrophils) is increased.


Become familiar with common chemotherapy side effects as well as long-term side effects of chemotherapy, but keep in mind that methods of controlling these symptoms have improved dramatically in recent years. For example, many people no longer experience nausea and vomiting even on the drugs most likely to cause these symptoms.

To make you days during chemo go just a little bit smoother, check out the essentials list of what to pack for chemotherapy.

A Word From Verywell

Combination chemotherapy can sometimes work to extend life, reduce the risk of cancer recurrence, or improve the results from immunotherapy. That said, adding more medications can increase the side effects and rigor of treatment.

While many people dread chemotherapy, it's important to note that very significant advances have occurred in managing these effects. For example, anti-nausea drugs can now greatly reduce or even eliminate nausea due to the drugs most likely to cause it. Likewise, injections such as Neulasta or Neupogen (drugs that increase the white blood cell count) are allowing doctors to use higher (and more effective) doses of chemotherapy drugs than was previously possible.

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  1. Hu M, Huang P, Wang Y, et al. Synergistic Combination Chemotherapy of Camptothecin and Floxuridine through Self-Assembly of Amphiphilic Drug-Drug Conjugate. Bioconjugate Chemistry. 2015. 26(12):2497-506. doi:10.1021/acs.bioconjchem.5b00513

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