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.
Kaldor
J M
JM
International Agency for Research on Cancer, Lyon, France.
Day
N E
NE
Pettersson
F
F
Clarke
E A
EA
Pedersen
D
D
Mehnert
W
W
Bell
J
J
Høst
H
H
Prior
P
P
Karjalainen
S
S
D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives; D016022:Case-Control Studies; D002699:Chlorambucil / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects; D005260:Female; D006801:Humans; D007938:Leukemia / Q000139:chemically induced*; D008558:Melphalan / Q000009:adverse effects; D015337:Multicenter Studies as Topic; D009378:Neoplasms, Multiple Primary; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000628:therapy; D012042:Registries; D012307:Risk Factors; D013852:Thiotepa / Q000009:adverse effects
D000970:Antineoplastic Agents; D002699:Chlorambucil; D003520:Cyclophosphamide; D013852:Thiotepa; C018404:treosulfan; D002066:Busulfan; D008558:Melphalan