What Is Combination Chemotherapy?

Combination chemotherapy is the use of more than one medication at a time to treat cancer. 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, multiple drugs may increase the risk of drug interactions. If there is such a problem, it may be challenging to determine which drug is to blame so that treatment can be adjusted.

To address this potential risk and elevate the likelihood treatment will be effective, chemotherapy is sometimes used along with a type of immunotherapy.

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 treating 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.

In the 1970s, combination chemotherapy was found to be more effective than single drugs for people with lung cancer, as well as more effective than "sequential chemotherapy"—i.e., using chemotherapy drugs one after the other.

In the last two decades, a new class of cancer drugs broadly labeled "targeted therapies" has appeared. These drugs don't work by destroying cancer cells the way chemotherapy does. Instead, they block specific pathways that are relatively exclusive to the cancer cells, inhibiting their growth or promoting their death without affecting healthy tissue of the body as much as chemotherapy would. These new targeted therapies include enzyme blockers, receptor blockers, immunotherapies and others. They have also been used in combination with chemotherapy with encouraging results.

Uses

There are many combinations of chemotherapy drugs used to treat 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 with breast cancer, combining two drugs—often Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed later by Taxol (paclitaxel)—has been found effective.

Leukemias and Lymphomas

With some leukemias and Hodgkin lymphoma, several chemotherapy drugs may be used together. Combination chemotherapy has greatly increased survival rates of 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).

Chemotherapy + Immunotherapy

When chemotherapy is used along with immunotherapy, benefits may go beyond using the combination of drugs. Immunotherapy drugs work 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 checkpoint inhibitors.

Benefits

There are several theoretical advantages to using a combination of chemotherapy medications rather than single agents.

Decreased Resistance

Using a combination of drugs may decrease the chance 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.

Earlier Administration

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.

Multidimensional Offense

Cancer is a complex disease involving many steps. Using more than one drug at a time makes it possible to target several processes in a cancer's growth at the same time.

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.       

More Effective                                           

Scientists use the term tumor heterogeneity to describe how the cancer cells in tumors vary from each other.

The initial cells in a cancer are identical. But as cancer cells continue to divide, they develop successively more mutations. This means 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.

By using different drugs at the same time, treatment can account for the fact that, due to heterogeneity, some cancer cells may respond to one drug, while other cancer cells may only respond to another drug.

Lower Doses

When a combination of chemotherapy medications are used at the same time, each can be administered at lower-than-normal dosages. This may reduce reduce the likelihood of toxic effects.

Synergy

There are some drugs that, when combined, produce an effect that is greater than the sum of their individual effects.

In practice, combination chemotherapy has either been found to improve survival or result in a better response to treatment. This has been especially true when chemotherapy is used as an adjuvant treatment.

This type of treatment is 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, because metastatic breast cancer 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 include the following.

More Side Effects

It goes without saying that more medications means a greater risk of side effects.

This applies to chemotherapy side effects, the likelihood of which is higher when more than one drug is used.

What's more, when more than one drug is used, side effects present with both drugs may compound. 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.

Side Effects Without a Confirmed Cause

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 because of a particular medication, but reactions between medications.

The more medications a person is using (both chemotherapy drugs and other medications), the greater the chance that an interaction will occur.

A Word From Verywell

Combination chemotherapy can sometimes work to extend life, reduce the risk of cancer recurrence, and/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, Neupogen, or Ryzneuta (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.