Leukemia following chemotherapy for ovarian cancer

Article Abstract:

Patients with ovarian cancer who receive chemotherapy in the form of alkylating agents are at risk for developing acute leukemia. No previous study has included enough subjects to draw conclusions about the risk and probable timing of leukemia associated with the specific drugs used for chemotherapy. It is important to determine which of the chemotherapeutic regimens that are effective against ovarian cancer have the least likelihood of inducing leukemia. An international study was carried out with the cooperation of 11 cancer registries and two large cancer hospitals in Europe and Canada. Of 99,113 women who survived ovarian cancer, 114 subsequently developed leukemia. Three control subjects were matched to each patient with leukemia in order to evaluate the leukemic potential of chemotherapy and radiotherapy (radiation treatments). The relative risk for developing leukemia after ovarian cancer was 12.0 for chemotherapy alone, 9.8 for both radiotherapy and chemotherapy, 1.6 for radiotherapy alone and 1.0 for surgery only. The difference in risk between radiotherapy only and surgery only was not considered significant; they were associated with equivalent levels of risk for leukemia. The chance of developing leukemia was greatest four to five years after chemotherapy was initiated, but continued to be high for at least eight years after chemotherapy was stopped. Drugs that were associated with increased risk for leukemia were cyclophosphamide, chlorambucil, melphalan, thiotepa and treosulfan, as was the combination of cisplatin and doxorubicin hydrochloride; the degree of risk varied among these drugs. The study did not evaluate how well the effectiveness of these drugs for fighting ovarian cancer offset the increased risk for leukemia. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Treatment-related leukemia

Article Abstract:

Chemotherapeutic treatment for Hodgkin's disease and ovarian cancer can increase the patient's risk of developing leukemia. Two articles by Kaldor et al. in the January 4, 1990 issue of 'The New England Journal of Medicine' evaluated the incidence of leukemia in patients who had undergone chemotherapy and other treatments for these two types of cancer. Both studies included large numbers of patients and matched each patient who developed leukemia to three patients who did not; this is called the case-control method. While bias in the matching process can interfere with the accuracy of results, Kaldor et al. designed the studies appropriately to avoid this problem. The studies show that risk for leukemia may be affected by the stage of the original cancer (ovarian cancer or Hodgkin's disease) and the dose of chemotherapy given. The Kaldor results confirm the impression given by other studies that development of leukemia is directly related to the previous treatments used for ovarian cancer and Hodgkin's disease. Since chemotherapy is provided in order to improve the chance of surviving the original cancer, this potential benefit must be weighed against the risk of developing leukemia. In Hodgkin's disease, a comparison of risks and benefits suggests that use of intensive combination chemotherapy is justified, but in ovarian cancer, intensive combination chemotherapy is not recommended on the basis of these studies. (Consumer Summary produced by Reliance Medical Information, Inc.)

editorial

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Leukemia following Hodgkin's disease

Article Abstract:

Patients with Hodgkin's disease who are treated with chemotherapy drugs called alkylating agents have a higher than normal risk of developing leukemia in the 10 years following chemotherapy. Previous studies have not evaluated the specific risk factors for leukemia in these patients. A large multicenter study was conducted at 18 hospitals and cancer registries in Europe and Canada; of 29,552 patients with Hodgkin's disease, 163 developed leukemia. The relative risk of leukemia following various treatments was found to be 9.0 for chemotherapy alone, 7.7 for chemotherapy and radiotherapy, and 1.0 for radiotherapy (radiation treatments) alone. While radiotherapy alone carried the lowest risk for leukemia, risk did increase as radiation dose increased. Specific chemotherapeutic drugs that seemed to elevate risk the most were procarbazine and mechlorethamine; when given together for more than six treatment cycles, risk was 14 times the risk of radiotherapy alone. Patients whose spleens had been removed had a risk of leukemia that was at least twice as great as patients whose spleens had not been removed. Patients with more advanced Hodgkin's disease also had a higher risk of leukemia. Chemotherapy to treat Hodgkin's disease substantially increases the risk for leukemia, and risk is related to medication dose but is not influenced by the additional use of radiation therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

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