How does chemotherapy affect the risk of second cancers?

Some types of chemotherapy (chemo) drugs have been linked with different kinds of second cancers. The cancers most often linked to chemo are myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Sometimes, MDS occurs first, then turns into AML. Acute lymphocytic leukemia (ALL) has also been linked to chemo. Chemo is known to be a greater risk factor than radiation therapy in causing leukemia.

Some solid tumor cancers have also been linked to chemo treatment for certain cancers, such as testicular cancer.

Alkylating agents

Alkylating agents are chemo drugs that interfere with a cell’s DNA in a certain way. These drugs can sometimes cause AML and MDS. Often MDS develops first, which then progresses to AML.

Alkylating agents known to cause leukemia include:

  • Mechlorethamine
  • Chlorambucil
  • Cyclophosphamide (Cytoxan®)
  • Melphalan
  • Lomustine (CCNU)
  • Carmustine (BCNU)
  • Busulfan

The risk gets higher with higher drug doses, longer treatment time, and higher dose-intensity (more drug given over a short period of time). Studies have shown that leukemia risk begins to rise about 2 years after treatment with alkylating agents, becomes highest after 5 to 10 years, and then declines.

Unfortunately, MDS and leukemia that develop after treatment with alkylating agents tend to be hard to treat.

Platinum-based drugs

The chemo drugs cisplatin and carboplatin are not an alkylating agents, but they attack cancer cells in much the same way. These drugs seem to increase the risk of leukemia (mainly AML), too, but the risk is not as great as with the alkylating agents. This leukemia tends to be hard to treat, much like the leukemia linked to the alkylating agents.

The risk of leukemia rises as the amount of drug used gets higher. The risk of developing leukemia increases even more if radiation is given along with cisplatin or carboplatin.

Topoisomerase II inhibitors

These chemo drugs stop cells from being able to repair DNA. These drugs can also cause leukemia, mainly AML.

Leukemia develops sooner after treatment with these drugs than the leukemia from alkylating agents. Most cases are found within 2 or 3 years of treatment and without MDS occurring first.

Drugs in this class include

  • Etoposide (VP-16)
  • Teniposide
  • Mitoxantrone (Novantrone®)

Drugs called anthracyclines are also topoisomerase II inhibitors. Anthracyclines are less likely to cause leukemia than the other topoisomerase II inhibitors. Examples of anthracyclines include:

  • Doxorubicin (Adriamycin®)
  • Daunorubicin
  • Epirubicin (Ellence®)
  • Idarubicin

Leukemia from topoisomerase II inhibitors tends to respond to better to treatment and has a better outlook than the leukemia from alkylating agents.

Targeted therapy drugs

Some drugs used to treat cancer are called targeted therapy drugs because they were designed to fight cancer by targeting certain genes or proteins.

Vemurafenib (Zelboraf®) and dabrafenib (Tafinlar®) are drugs that target the BRAF protein. They are used to treat melanoma and are being studied for use in other cancers. People taking these drugs have a higher risk of squamous cell carcinomas of the skin.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: December 11, 2014 Last Revised: February 16, 2017

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