Some Antiviral and Antineoplastic Drugs and other Pharmaceutical Agents, Volume 76 (IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans)

531 Pages·2000·1.59 MB·English

by  The International Agency for Research on Cancer

WORLD HEALTH ORGANIZATION
INTERNATIONALAGENCYFOR RESEARCH ON CANCER
IARC MONOGRAPHS
ON THE
EVALUATION OF CARCINOGENIC
RISKS TO HUMANS
Some Antiviral and Antineoplastic Drugs,
and Other Pharmaceutical Agents
VOLUME 76
This publication representsthe views and expert opinions
of an IARC Working Group on the
Evaluation of Carcinogenic Risks to Humans,
which met in Lyon,
12–19 October 1999
2000
IARC MONOGRAPHS
In 1969, the International Agency for Research on Cancer (IARC) initiated a programme
on the evaluation of the carcinogenic risk of chemicals to humans involving the production of
critically evaluated monographs on individual chemicals. The programme was subsequently
expanded to include evaluations of carcinogenic risks associated with exposures to complex
mixtures, life-style factors and biological and physical agents, as well as those in specific
occupations.
The objective of the programme is to elaborate and publish in the form of monographs
critical reviews of data on carcinogenicity for agents to which humans are known to be
exposed and on specific exposure situations; to evaluate these data in terms of human risk
with the help of international working groups of experts in carcinogenesis and related fields;
and to indicate where additional research efforts are needed.
The lists of IARC evaluations are regularly updated and are available on Internet:
http://www.iarc.fr/, under Publications.
This project was supported by Cooperative Agreement 5UO1CA33193 awarded by the
United States National Cancer Institute, Department of Health and Human Services. Additional
support has been provided since 1986 by the European Commission, since 1993 by the United
States National Institute of Environmental Health Sciences and since 1995 by the United States
Environmental Protection Agency through Cooperative Agreement Assistance CR 824264.
©
International Agency for Research on Cancer, 2000
Distributed by IARCPress(Fax: [phone]; E-mail: [email protected])
and by the World Health Organization Distribution and Sales, CH-1211 Geneva 27
(Fax: [phone]; E-mail:[email protected])
Publications of the World Health Organization enjoy copyright protection in accordance
with the provisions of Protocol 2 of the Universal Copyright Convention.
All rights reserved. Application for rights of reproduction or translation, in part or in toto,
should be made to the International Agency for Research on Cancer.
IARC Library Cataloguing in Publication Data
Some antiviral and antineoplastic drugs, and other pharmaceutical agents /
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans
(2000 :Lyon, France).
(IARC monographs on the evaluation of carcinogenic risks to humans ; 76)
1. Carcinogens – congresses 2. Drugs – congresses
I. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans
II. Series
ISBN 92 832 1276 2 (NLM Classification: W1)
ISSN 1017-1606
PRINTED IN FRANCE
CONTENTS
NOTE TO THE READER............................................................................................1
LISTOF PARTICIPANTS............................................................................................3
PREAMBLE ................................................................................................................9
Background ............................................................................................................9
Objective and Scope ..............................................................................................9
Selection of Topics for Monographs....................................................................10
Data for Monographs............................................................................................11
The Working Group..............................................................................................11
Working Procedures..............................................................................................11
Exposure Data ......................................................................................................12
Studies of Cancer in Humans ..............................................................................14
Studies of Cancer in Experimental Animals........................................................17
Other Data Relevant to an Evaluation of Carcinogenicity
and its Mechanisms........................................................................................20
Summary of Data Reported..................................................................................22
Evaluation ............................................................................................................23
References ............................................................................................................27
GENERALREMARKS..............................................................................................33
THE MONOGRAPHS................................................................................................43
Antiretroviral agents..........................................................................................45
Aciclovir ........................................................................................................47
Zidovudine (AZT)..........................................................................................73
Zalcitabine....................................................................................................129
Didanosine....................................................................................................153
DNAtopoisomerase II inhibitors....................................................................175
Etoposide......................................................................................................177
Teniposide ....................................................................................................259
Mitoxantrone................................................................................................289
Amsacrine ....................................................................................................317
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iv IARC MONOGRAPHS VOLUME 76
Otherpharmaceutical agents..........................................................................345
Hydroxyurea ................................................................................................347
Phenolphthalein............................................................................................387
Vitamin K substances ..................................................................................417
SUMMARYOF FINALEVALUATIONS ..............................................................487
CUMULATIVE INDEX TO THE MONOGRAPHS SERIES................................489
NOTE TO THE READER
The term ‘carcinogenic risk’in the IARC Monographs series is taken to mean the
probability that exposure to an agent will lead to cancer in humans.
Inclusion of an agent in the Monographsdoes not imply that it is a carcinogen, only
that the published data have been examined. Equally, the fact that an agent has not yet
been evaluated in a monograph does not mean that it is not carcinogenic.
The evaluations of carcinogenic risk are made by international working groups of
independent scientists and are qualitative in nature. No recommendation is given for
regulation or legislation.
Anyone who is aware of published data that may alter the evaluation of the carcino-
genic risk of an agent to humans is encouraged to make this information available to the
Unit of Carcinogen Identification and Evaluation, International Agency for Research on
Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France, in order that the agent
may be considered for re-evaluation by a future Working Group.
Although every effort is made to prepare the monographs as accurately as possible,
mistakes may occur. Readers are requested to communicate any errors to the Unit of
Carcinogen Identification and Evaluation, so that corrections can be reported in future
volumes.
–1–
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IARC WORKING GROUPON THE EVALUATION
OF CARCINOGENIC RISKS TO HUMANS:
SOME ANTIVIRALAND ANTINEOPLASTIC DRUGS,
AND OTHER PHARMACEUTICALAGENTS
Lyon, 12–19 October 1999
LIST OF PARTICIPANTS
Members
D.E. Barker, The CORE Center for Infectious Diseases, Cook County Hospital, Division
of Infectious Diseases, 2020 W. Harrison Street, Chicago, IL60612, United States
T.A. Dragani, Istituto Nazionale dei Tumori, via G. Venezian 1, 20133 Milan, Italy
J.K. Dunnick, National Institute of Environmental Health Sciences, PO Box 12233,
Research Triangle Park, NC27709, United States
C.A. Felix, Division of Oncology, The Children’s Hospital of Philadelphia, Abramson
Pediatric Research Center, Room 902B, 3516 Civic Center Boulevard, Philadelphia,
PA19104-4318, United States
L.R. Ferguson, Auckland Cancer Society Research Centre, Faculty of Medical and
Health Science, The University of Auckland, Private Bag 92019, Auckland 1000,
New Zealand
S.P. Joel, Medical Oncology, St Bartholomew’s Hospital, West Smithfield, London
EC1A7BE, United Kingdom
R. von Kries, Institute for Social Pediatrics and Adolescent Medicine, Ludwig-
Maximilians University, Heiglhofstrasse 63, 81377 Munich, Germany
F.E. van Leeuwen, Department of Epidemiology, The Netherlands Cancer Institute,
Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
J. Little, Institute of Medical Sciences, Department of Medicine & Therapeutics,
University of Aberdeen Medical School, Polwarth Building, Foresterhill, Aberdeen
AB9 2ZD, United Kingdom
S. Olin, International Life Sciences Institute, Risk Science Institute, 1126 Sixteenth
Street NW, Washington, DC 20036, United States
J.H. Olsen, Danish Cancer Society, Institute of Cancer Epidemiology, Box 839, 2100
Copenhagen Ø, Denmark
–3–
4 IARC MONOGRAPHS VOLUME 76
M.C. Poirier, Carcinogen–DNAInteractions Section, National Cancer Institute, Building
37, Room 2A05, 37 Convent Drive, Bethesda, MD 20892-4255, United States
(Chairperson)
M.J. Shearer, The Vitamin K Research Unit of the Haemophilia Centre, The Rayne
Institute, 4th Floor Lambeth Wing, St Thomas’s Hospital, London SE1 7EH, United
Kingdom
W. Slikker, Jr, Division of Neurotoxicology, National Center for Toxicological Research,
Food and Drug Administration, Jefferson, AR72079-9502, United States
F.M. Sullivan, Harrington House, 8 Harrington Road, Brighton, East Sussex BN1 6RE,
United Kingdom
V. Turusov, Blokhin Cancer Research Centre, Russian Academy of Medical Sciences,
Kashirskoye Shosse 24, 115478 Moscow, Russian Federation
V.E. Walker, Wadsworth Center for Laboratories and Research, New York State
Department of Health, Empire State Plaza, POBox 509, Albany, NY 12201-0509,
United States
Representative/Observer
Representative of the National Cancer Institute
S.M. Sieber, Division of Cancer Epidemiology and Genetics, National Cancer Institute,
Executive Plaza North, 6100 Executive Boulevard, Rockville, MD 20852, United
States
Secretariat
E. Heseltine (Editor), Lajarthe, 24290 St Léon-sur-Vézère, France
IARC
R. Baan, Unit of Carcinogen Identification and Evaluation
P. Brennan, Unit of Environmental Cancer Epidemiology
M. Friesen, Unit of Gene–Environment Interactions
Y. Grosse, Unit of Carcinogen Identification and Evaluation
V. Krutovskikh, Unit of Multistage Carcinogenesis
C. Malaveille, Unit of Endogenous Cancer Risk Factors
D. McGregor, Unit of Carcinogen Identification and Evaluation
C. Partensky, Unit of Carcinogen Identification and Evaluation
J. Rice, Unit of Carcinogen Identification and Evaluation (Head of Programme)
J. Wilbourn, Unit of Carcinogen Identification and Evaluation (Responsible Officer)
Technical assistance
M. Lézère
A. Meneghel
D. Mietton
J. Mitchell
PARTICIPANTS 5
E. Perez
S. Reynaud
J. Thévenoux