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Does chemotherapy cause cancer?
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Patients with cancer who undergo chemotherapy may be at elevated risk for a new primary cancer several years later.
The most common secondary cancers that occur in chemotherapy-treated patients include myelodysplastic syndrome, acute myelogenous leukemia, acute lymphocytic leukemia and testicular cancer.
Alkylating agents
A person’s bone marrow stem cells can be damaged by cancer treatments known as alkylating agents, the first class of chemotherapy agents used. These agents increase the risk for myelodysplastic syndrome or AML. In some cases, myelodysplastic syndrome develops and later transforms into AML.
Higher drug doses, higher dose intensity and lengthier treatment time appear to increase risks for secondary cancers in patients treated with alkylating agents.
Research suggests the risk for leukemia begins to increase approximately 2 years after treatment with alkylating agents. The risk increases even more after 5 to 10 years and tapers off thereafter.
Secondary cancers that develop from treatment with alkylating agents are more likely to be difficult to treat, and they often are associated with poor outcomes.
Other chemotherapy types
The nonalkylating agents cisplatin and carboplatin combat cancer cells in a manner similar to alkylating agents.
In general, the risk for posttreatment leukemia is not as high. However, leukemia risk increases when radiation is administered along with either cisplatin or carboplatin.
Other chemotherapy agents known as topoisomerase II inhibitors also increase the risk for leukemia, specifically AML, according to the American Cancer Society. Unlike leukemia that develops years after treatment with alkylating agents, leukemia that develops from these chemotherapy agents occurs soon after treatment initiation. Most patients are diagnosed within 2 to 3 years after primary cancer treatment. However, leukemia that develops after treatment with topoisomerase II inhibitors is more likely to respond to treatment and is associated with better outcomes than leukemia that develops after treatment with alkylating agents.
Treatment evolution
Advances in cancer treatment have led to higher survival rates. Consequently, as the number of cancer survivors increases, so does the risk for secondary cancers in this population.
The challenge for researchers is to design cancer treatments that maximize patient survival while minimizing the risks for secondary cancers.
Lindsay Morton, PhD, of the NCI, and colleagues reviewed data from SEER registries on patients aged 20 to 84 years who were diagnosed with cancer between 1975 and 2008 and received chemotherapy.
Results, published in 2013 in Blood, showed patients with myeloma continue to be at the greatest risk for treatment-related AML, primarily due to the ongoing use of melphalan.
Researchers observed a decreased risk over time for treatment-related cancers among patients with breast cancer, a decline attributed to the increased use of cyclophosphamide-based treatment.
The investigators also observed a similar decline in treatment-related cancers among women who underwent treatment with a less toxic platinum-based therapy for ovarian cancer.
Researchers now are trying to determine which patients will derive the most benefit from chemotherapy. This will allow the patients least likely to benefit from chemotherapy to be spared from its potentially harmful side effects.
The MINDACT trial, presented at the American Association for Cancer Research Annual Meeting, was the first prospective randomized controlled trial of a breast cancer recurrence genomic assay with level one clinical evidence.
Researchers compared the 70-gene signature MammaPrint (Agendia) with traditional clinical assessments to determine which patients with early-stage breast cancer could safely forego adjuvant chemotherapy.
Use of the 70-gene signature assay was associated with a 46% decrease in chemotherapy prescriptions among patients determined to be at clinically high risk for breast cancer.
The findings could “de-escalate the use of adjuvant chemotherapy and spare many patients an aggressive treatment they will not benefit from,” said researcher Martine Piccart, MD, PhD, head of the medicine department at Jules Bordet Institute in Belgium.
For more information:
www.cancer.net/survivorship/long-term-side-effects-cancer-treatment