Acute Nonlymphocytic Leukemia after Therapy with Alkylating Agents for Ovarian Cancer: A Study of Five Randomized Clinical Trials

We evaluated the occurrence of acute nonlymphocytic leukemia (and) among 1399 women with ovarian cancer who were treated in five randomized clinical trials. Of the 1399 women, 998 had been treated with alkylating agents, and among these, 12 cases of and were observed; the expected number was 0.11. T...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The New England journal of medicine 1982-12, Vol.307 (23), p.1416-1421
Hauptverfasser: Greene, Mark H, Boice, John D, Greer, Benjamin E, Blessing, John A, Dembo, Alon J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:We evaluated the occurrence of acute nonlymphocytic leukemia (and) among 1399 women with ovarian cancer who were treated in five randomized clinical trials. Of the 1399 women, 998 had been treated with alkylating agents, and among these, 12 cases of and were observed; the expected number was 0.11. Ten patients with and had received melphalan, and two chlorambucil, and was not observed in 401 women who had been treated with surgery or radiation or both, without alkylating agents. The excess risk of and that was associated with alkylating-agent therapy was 5.8 cases per 1000 women per year, and the cumulative seven-year risk of and was 9.6±3.3 per cent (±S.E.). The risk of and among patients who were treated with chemotherapy alone was indistinguishable from that observed in patients receiving both radiation and chemotherapy. A positive correlation between initial drug dose and the risk of and was suggested. These data underscore the need to assess other cytotoxic agents and regimens of drug administration to identify those that do not have harmful late effects. (N Engl J Med. 1982; 307:1416–21.) Experimental data have long indicated that some anti-cancer drugs, particularly the alkylating agents, are carcinogenic in laboratory animals. 1 Until recently, evidence that these agents have similar effects in human beings has been anecdotal. During the past five years, however, a series of analytic studies have documented excesses of acute nonlymphocytic leukemia (and) in patients treated for Hodgkin's disease, 2 3 4 multiple myeloma, 5 6 non-Hodgkin's lymphoma, 7 , 8 polycythemia vera, 9 and ovarian cancer. 10 , 11 Studies of women with ovarian cancer have been particularly informative, since an intrinsic predisposition to and has been clearly ruled out. 10 Furthermore, the leukemogenic effects of radiation alone, alkylating agents alone, and both . . .
ISSN:0028-4793
1533-4406
DOI:10.1056/NEJM198212023072302