LEUKEMIA FOLLOWING CHEMOTHERAPY FOR OVARIAN-CANCER

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case–control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk, as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known. IT has been clearly demonstrated that patients who have received chemotherapy with alkylating agents for ovarian cancer have an increased risk of acute leukemia, particularly the myeloid type.1 2 3 4 5 6 Although the drugs treosulfan, melphalan, chlorambucil, and cyclophosphamide have all been identified as leukemogenic,7 most previous studies have not been large enough to permit detailed analyses of the risk and the time of occurrence of leukemia according to the amount and type of chemotherapy received. Since several different drugs and combinations of drugs currently used to treat ovarian cancer cannot be clearly distinguished in terms of their therapeutic effects (Tamar M: personal… © 1990, Massachusetts Medical Society. All rights reserved.