Cancer Management in Man: Biological Response Modifiers, Chemotherapy, Antibiotics, Hyperthermia, Supporting Measures

257 Pages·1989·12.24 MB·English

by  Robert K. Oldham (auth.)

CANCER MANAGEMENT IN MAN
Biological Response Modifiers, Chemotherapy,
Antibiotics, Hyperthermia, Supporting Measures
Cancer Growth and Progression
SERIES EDITOR: HANS E. KAISER
Department of Pathology, University of Maryland, Baltimore, Md, U.S.A.
Scientific Advisors:
Kenneth W. Brunson / Harvey A. Gilbert / Ronald H. Goldfarb / Alfred L. Goldson / Elizier Gorelik /
Anton Gregl / Ronald B. Herberman / James F. Holland / Ernst H. Krokowski t / Arthur S. Levine /
Annabel G. Liebelt / Lance A. Liotta / Seoras D. Morrison / Thkao Ohnuma / Richard L. Schilsky /
Harold L. Stewart / Jerome A. Urban / Elizabeth K. Weisburger / Paul V. Woolley
Volume 1: Fundamental Aspects of Cancer
Volume Editor: Ronald H. Goldfarb
ISBN 0-89838-990-9
Volume 2: Mechanisms of Carcinogenesis
Volume Editor: Elizabeth K. Weisburger
ISBN 0-89838-991-7
Volume 3: Influence of Tumor Development on the Host
Volume Editor: Lance A. Liotta
ISBN 0-89838-992-5
Volume 4: Influence of the Host on Tumor Development
Volume Editor: Ronald B. Herberman
ISBN 0-89838-993-3
Volume 5: Comparative Aspects of Tumor Development
Volume Editor: Hans E. Kaiser
ISBN 0-89838-994-1
Volume 6: Etiology of Cancer in Man
Volume Editor: Arthur S. Levine
ISBN 0-89838-995-X
Volume 7: Local Invasion and Spread of Cancer
Volume Editor: Kenneth W. Brunson
ISBN 0-89838-996-8
Volume 8: Metastasis / Dissemination
Volume Editor: Elizier L. Gorelik
ISBN 0-89838-997-6
Volume 9: Cancer Management in Man: Detection, Diagnosis, Surgery, Radiology, Chronobiology,
Endocrine Therapy
Volume Editor: Alfred L. Goldson
ISBN 0-89838-998-4
Volume 10: Cancer Management in Man: Biological Response Modifiers, Chemotherapy, Antibiotics,
Hyperthermia, Supporting Measures
Volume Editor: Paul V. Woolley
ISBN 0-89838-999-2
Complete set: ISBN 0-89838-989-5
Cancer Management in Man
Biological Response Modifiers, Chemotherapy, Antibiotics,
Hyperthermia, Supporting Measures
Edited by
PAUL V. WOOLLEY
Division of Oncology
Vincent T. Lombardi Cancer Research Center
Georgetown University School of Medicine
Washington, D.C., U.S.A.
Kluwer Academic Publishers
DORDRECHT / BOSTON / WNDON
Library of Congress Cataloging in Publication Data
Cancer management in man: biological response modifiers,
chemotherapy. antibiotics. hyperthermia. supporting measures
edited by Paul U. Woolley.
p. cm. -- (Cancer growth and progression; 10)
Includes index.
ISBN -13: 978-94-010-6983-0 e-ISBN-13:978-94-009-1095-9
DOl: 10.1007/978-94-009-1095-9
1. Cancer--Treatment--Congresses. 2. Biological response
modifiers--Therapeutic use--Congresses. 3. Cancer--Immunotherapy
-Congresses. 4. Cancer--Chemotherapy--Congresses. 5. Cancer-
-Adjuvant treatment--Congresses. I. Woolley. Paul V. II. Series:
Cancer growth and progression; v. 10.
[DNLM- 1. Antineoplastic Acents. 2. Neoplasms--drug therapv.]
RC270.8.C362 1989 -
616.99'406--dc19
DNLM/DlC
for Library of Congress 88-23018
CIP
ISBN-13: 978-94-010-6983-0
Published by Kluwer Academic Publishers,
p.o. Box 17,3300 AA Dordrecht, The Netherlands.
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Cover design by Jos Vrolijk.
All rights reserved
© J 989 by Kluwer Academic Publishers
Softcover reprint of the hardcover 1st edition J 989
No part of the material protected by this copyright notice may be reproduced or utilized in any form
or by any means, electronic or mechanical, including photocopying, recording, or by any information
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INTRODUCTION
This volume, the last in this series on cancer growth and Moreover, the current status of plant-derived vinca alka
progression, is a companion volume to Volume IX and loids and non-alkaloid natural products is summarized.
further explores established and novel approaches for the Advances in hyperthermia and additional approaches for
therapy of patients with malignant neoplasms. The stra the therapy of malignancies are also presented.
tegies reflected in these volumes are direct extrapolations The volume continues with chapters on bone marrow
from the basic science of cancer biology, growth and pro transplantation as well as hematologic and nutritional sup
gression described in earlier volumes of this series. Some port for the cancer patient. Blood pressure in the cancer
approaches are directed towards the eradication or modifi patient, therapy for nausea and vomiting as well as pain are
cation of the properties of heterogeneous malignant tumor discussed. The last chapter is devoted to the problems of the
cells at various stages of tumor progression, while other terminally ill, including evaluations of the burden relatives
approaches are directed towards modification of the host and friends of the cancer patient have to bear.
antitumor defense systems, e.g., enhancement of host anti It is clear that important advances in the basic science of
tumor immune reactivity. cancer growth and progression (reviewed in Volumes I-IV
The chapters reviewing immunotherapy and biological of this series) coupled with an understanding of cancer in
response modifiers in cancer treatment indicate how man as compared to other species (Volume V), and an
advances in the basic science of cancer biology and tumor understanding of the etiology of cancer in man (Volume VI),
immunology (see Volumes I-IV) have been rapidly extended local invasion and spread of cancer in man (Volume VII),
to clinical strategies for therapy of human neoplasms. In and patterns of metastasis/dissemination in man (Volume
deed, these new approaches may yield effective modalities VIII) are all essential features for the formulation of new
for cancer treatment with a high margin of safety and effi advances in cancer management for human neoplasms. The
cacy with the capacity to overcome conventional drug resis recent and substantial advances in cancer management re
tance and tumor heterogeneity. Additional approaches viewed in this volume, and in Volume IX, indicate the rapid
towards cancer treatment, as well as advances in conven and expanding progress that will continue to emerge from
tional treatment are also reviewed in this volume and in this continuum of basic sciences, preclinical studies in
clude: transcatheter management, antifolates, purine metab therapy and diagnosis models in animals, and ultimate ex
olites, alkylating agents, platinum compounds, nitro trapolation to the management of cancer in man.
soureas, triazine and hydrazine derivatives, anthracycline
antibiotics, actinomycin and other antitumor antibiotics. Series Editor Volume Editor
Hans E. Kaiser Paul V. Woolley
TABLE OF CONTENTS
Introduction . . . . . . . . . V
List of Contributors. . . . . . IX
1. Biological response modifiers
R.K. OLDHAM. . .
2. Antitumor effects of interferons
R.M. FRIEDMAN and R.K. OLDHAM . 9
3. Transcatheter management of neoplasms
e.H. CARRASCO, S. WALLACE, e. CHARNSANGAVEJ and W. BECHTEL. 21
4. Antifolates
M.G. NAIR. . . . . . . . . . 35
5. Purine antimetabolites
W. SADEE and B.T. NGUYEN. 54
6. Alkylating agents
D.E.V. WILMAN and P.B. FARMER. 63
7. Platinum compounds
C.L. LITTERST and E. REED 85
8. Nitrosoureas
G. POWIS . . . . . . . 98
9.Triazine and hydrazine derivatives
G. POWIS . . . 113
10. Anthracyc1ine antibiotics
N.R. BACHUR. . . . . 125
11. Actinomycin
D.L. ANTON and P.A. FRIEDMAN 131
12. Other antitumor antibiotics
G.R. LYNCH and M. LANE . 134
13. Plant alkaloids: the vinca alkaloids
M.e. CASTLE . . . . . . . 147
14. Non-alkaloid natural products as anticancer agents
D.G.I. KINGSTON 152
15. Hyperthermia
M.W. DEWHIRST. . . . . . . . . . . . 159
16. Current advances in bone marrow transplantation for cancer treatment
D.V. KIRKPATRICK and L. DELMONTE 165
17. Hematologic support of the patient with malignancy
J.e. PHARES. . . . . . . . . . . . . . . . . . . . . . 180
18. The sphygmochron for chronobiologic blood pressure and heart rate assessment in cancer patients
J. HALBERG, G. CORNELISSEN, FRANZ HALBERG, F. HALBERG and E. HALBERG. 189
19. Nutritional support of cancer patients during cancer progression
T. OHNUMA. . . . . . . . . . . . . . . . . . . . . . . . . 196
20. Palliative chemotherapy: Cancer chemotherapy-induced nausea and vomiting
J. LASZLO and V.S. LUCAS, Jr. . 204
21. Chronic pain management
R.M. FRANK. . . . . . . . . . . . . . . . . . . . . . . . . 207
22. Care for the terminally ill: Death and dying
H.E. KAISER, D.B. BROCK, D.J. FOLEY, H. MAIER-GERBER and T.A. HODGSON 216
Index of subjects . . . . . . . . . . . . . . . .. .................. 227
vii
Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative
biological and clinical point of view, was given by my late friend E. H. Krokowski.
Those engaged on the project included 252 scientists. listed as contributors. volume editors and scientific advisors, and a
dedicated staff. Special assistance was furnished by 1. P. Dickson, .J. A. Feulner, and I. Theloe.
I. Bauer, D. L. Fisher. S. Fleishman. K. Joshi. A. M. Lewis, J. Taylor and K. E. Yinug have provided additional assistance.
The firm support of the publisher. especially B. F. Commandeur. is deeply appreciated. The support of the University of
Maryland throughout the preparation of the series is acknowledged.
To the completion of this undertaking my wife. Charlotte Kaiser. has devoted her unslagging energy and invaluable support.
CONTRIBUTORS
David L. ANTON, PhD. Mark W. DEWHIRST, DVM, Ph.D.
Beth Israel Hospital Medical Center
Harvard Medical School Duke University
330 Brookline Avenue Durham, NC 27710, USA
Boston, MA 02215, USA
Current address: Peter B. FARMER, Ph.D.
E.I. Du Pont De Nemours & Company MRC Toxicology Unit Medical Research Council Laboratories
Wilmington, Delaware 19898, USA W oodmansterne Road
Carshalton, Surrey SM5 4EF, UK
Nicolas BACHUR, M.D.
Maryland Cancer Center DAN J. FOLEY, M.S.
University of Maryland Hospital Epidemiology, Demography & Biometry Program National
22 S. Greene Street Institute on Aging
Baltimore, MD 21201, USA 7550 Wisconsin Avenue
Bethesda, MD 20892, USA
William BECHTEL, M.D.
M.D. Anderson Hospital and Tumor Institute Robert M. FRANK, R.Ph.
6723 Bertner Avenue Department of Pharmacy
Houston, Texas 77030, USA Mount Sinai School of Medicine at The Mount Sinai Hospital
The Mount Sinai Medical Center of the City University
Dwight B. BROCK, Ph.D. of New York
Epidemiology, Demography & Biometry Program One Gustave L. Levy Place
National Institute on Aging New York, NY 10029, USA
7550 Wisconsin Ave
Bethesda, MD 20892, USA Paul A. FRIEDMAN, M.D.
Beth Israel Hospital
C. Humberto CARRASCO, M.D. Harvard Medical School
M.D. Anderson Hospital and Tumor Institute 330 Brookline Avenue
6723 Bertner Avenue Boston, MA 02215, USA
Houston, TX 77030, USA Current address:
Merck Sharp & Dohme Research Laboratories
Mickey C. CASTLE, Ph.D. Division of Merck & Co.
Department of Pharmacology West Point, PA 19486, USA
Eastern Virginia Medical School
P.O. Box 1980 Robert M. FRIEDMAN, M.D.
Norfolk, VA 23501, USA Department of Pathology
Uniformed Services University of the Health Sciences
Chulsip CHARNSANGAVEJ, M.D. 4301 Jones Bridge Road
M.D. Anderson Hospital and Tumor Institute Bethesda, MD 20814, USA
6723 Bertner Avenue
Houston, TX 77030, USA Erna HALBERG, B.S.
Health Sciences Center
Germaine CORNELISSEN, M.D. University of Minnesota
Chronobiology Laboratories Minneapolis, Monnesota 55455, USA
Department of Laboratory Medicine and Pathology
University of Minnesota Francine HALBERG, M.D.
Minneapolis, Minnesota 55455, USA Department of Radiation Oncology
University of California
Lilian DELMONTE, D.Sc. San Francisco, California 94115, USA
Biomedical Communication Consultant
440 East 62nd Street Franz HALBERG, M.D.
Apt.7E Chronobiology Laboratories
New York, NY 10021, USA Department of Laboratory Medicine and
formerly Memorial Sloan Kettering Cancer Center Pathology, University of Minnesota
New York, New York Minneapolis, MN 55455, USA
IX
X Contributors
Julia HALBERG, B.A., M.S., M.P.H., M.D. Binh T. NGUYEN, Ph.D.
St. Paul-Ramsey Medical Center Department of Pharmacy
St. Paul, Minnesota 55101, USA University of California, School of Pharmacy
San Francisco, CA 94143, USA
Thomas HODGSON, Ph.D.
National Center for Health Statistics Takao OHNUMA, M.D., Ph.D.
3700 East West Highway Department of Neoplastic Diseases
Hyattsville, MD 20782, USA The Mount Sinai Medical Center of the City University of
New York
Hans E. KAISER, D.Sc. One Gustave L. Levy Place
Department of Pathology New York, NY 10029, USA
University of Maryland, School of Medicine
10 S. Pine Street Robert K. Oldham, M.D.
Baltimore, MD 21201, USA BTl Biological Therapy Institute
Riverside Drive
David G.I. KINGSTON, Ph.D. Franklin TN 37064, USA
Department of Chemistry, College of Arts and Sciences
Virginia Polytechnic Institute and State University John C. PHARES, M.D.
Blacksburg, VA 24061, USA Hematology and Oncology
Naval Hospital
Dahlia V. KIRKPATRICK, M.D. Bethesda, MD 20814, USA
Pediatric Oncology, Department of Pediatrics
Tulane University Medical School Garth POWIS, D.phil.
New Orleans, LO 70112, USA Division of Developmental Oncology Research
Mayo Clinic
M. LANE, M.D. Rochester, MN 55905, USA
Baylor College of Medicine
One Baylor Plaza, Houston, TX 77030, USA Eddie REED, Ph.D.
National Cancer Institute
John LASZLO, M.D. National Institutes of Health
American Cancer Society, Inc. Bethesda, MD 20892, USA
3340 Peachtree Road, N.E.
Atlanta Georgia 30026, USA Wolfgang SADEE, PhD.
Department of Pharmacy
Charles L. LITTERST, M.D. University of California, School of Pharmacy
National Cancer Institute San Francisco, CA, 94143, USA
National Institutes of Health
Bethesda, MD 20891, USA Sidney WALLACE, M.D.
Department of Diagnostic Radiology
V. Sol Lucas, Jr., B.S. Pharm., R.Ph. The University of Texas, System Cancer Center
Burroughs Wellcome Company M.D. Anderson Hospital & Tlimor Institute
Research Triangle Park 6723 Bertner Ave., Houston, TX 77030, USA
NC 27709, USA
Derry E.V. WILMAN, Ph.D.
Garrett R. LYNCH, M.D. Institute of Cancer Resea~ch
Baylor College of Medicine Cancer Research Campaign Laboratory, Clifton Avenue
Medical Oncology, Ben Taub General Hospital Sutton, Surrey, England, UK
Houston, TX 77030, USA
Paul V. WOOLLEY, M.D.
Hartmut MAIER-GERBER, M.D. Division of Oncology
Langensteinbacherhoehe Vincent T. Lombardi Cancer Research Center
7510 Karlsbad b. Karlsruhe, FRG Georgetown University School of Medicine
3800 Reservoir Road, N.W.
Madhavan G. NAIR, Ph.D. Washington DC, 20007, USA
Department of Bioiphemistry
University of South Alabama
Mobile, AL 36688, USA
1
BIOLOGICAL RESPONSE MODIFIERS
ROBERT K. OLDHAM
ABSTRACT response;
(d) decrease transformation and/or increase differentia
Biotherapy represents a new modality of cancer treatment. It uti tion (maturation) of tumor cells;
lizes biologicals and biological response modifiers. Many of these (e) increase the ability of the host to tolerate damage by
substances are of 'natural' origin eminating from mammalian cells cytotoxic modalities of cancer treatment.
as physiologic mediators of immune response and as substances
While several of these approaches involve the augmen
active in the regulation of growth and maturation. With the advent
tation of biological responses, an understanding of the bio
of molecular biological techniques, hybridoma technology and
logical properties of immune response molecules, growth
computer applications, it is now possible to prepare these biological
substances in highly purified form and in large quantities for use as and maturation factors and other biological substances will
medicinals. The expertise required to apply these biotherapeutic assist in the development of specific molecular entities which
approaches to the treatment of cancer often involves the use of can have direct actions on biological responses and/or on
immunological and/or molecular biological capabilities. Because of tumor cells. Thus, one can visualize the development of
the rather specialized expertise needed to understand and apply biological approaches with response modifying as well as
these substances as anticancer approaches, those individuals with direct cytolytic, cytostatic, or maturational effects on tumor
expertise in the application of chemotherapy to patients with cancer
cells.
are not necessarily well prepared for the translation of biotherapy
It is clear that the mechanisms are now available for the
to the clinic. Biotherapeutic approaches are broad and involve a
development of biotherapy. To put these approaches into
whole range of physiological responses inherent in cancer biology.
The approaches needed to bring these biotherapeutic capabilities to clinical practice it is important to dispel a historical dogma
the clinic need to be considered carefully and the use of new tech of immunotherapy. Biotherapy can have activity on clini
niques and new methods of application should be encouraged so as cally apparent disease, and the testing is not restricted to
not to inhibit these potentially powerful anticancer approaches. As situations where the tumor cell mass is imperceptible (38).
natural mediators, many biologicals have much less inherent toxic Thus, the clinical trial designs for biotherapy can be similar
ity than the drugs previously used in systemic cancer therapy. to those used previously for other modalities of C<;lncer
Therefore, the systems for translating these substances from the
treatment, as long as one is sensitive to the need to measure
laboratory to the clinic should be restructured for the rapid trans
both pharmacokinetics and the biological responses affected
lation of biotherapy to the patient.
by these approaches (34). Thus, testing is continuing for the
interferons, lymphokines/cytokines, growth and maturation
INTRODUCTION factors, monoclonal antibodies and immunoconjugates
thereof, vaccines and cellular therapy.
Biologicals could encompass any substance of biological
origin but generally represent the products of the mam
malian genome. With modern techniques of genetic engi HISTORICAL PERSPECTIVES
neering the mammalian genome represents the new 'medi
cine cabinet'. Biological response modifiers (BRM) are Given the variability of cancer's clinical presentation, it is
agents and approaches whose mechanisms of action involve not surprising that randomized trials of nonspecific and
the individual's own biological responses. Biologicals and specific immunotherapy, as translated from animal models,
BRM can act in several ways in the biotherapy of cancer: have not been uniformly successful in cancer treatment (21,
(a) augment the host's defenses by administering cells, 22). Naturally occurring cancers arise in a particular organ
natural biologicals or the synthetic derivatives thereof as from one cell or a few cells under some carcinogenic stim
effectors or mediators (direct or indirect) of an antitumor urits. In humans, these initial foci of cancer cells may grow
response; over very long periods of time (from 1 % to 10 % of the
(b) increase the individual's antitumor responses through human life span) before there is any clinical evidence of the
augmentation and/or restoration or effector mechanisms disease. Dissemination of cells from initial focus may occur
and/or decrease a component of the host's reaction that may at any time during the development of the primary tumor.
be deleterious; Thus, growth and metastasis occur over months to years,
(c) augment the individual's responses using modified allowing complex biological interactions to take place.
tumor cells or vaccines to stimulate a greater response by the By contrast, experimentally induced cancer is an artificial
individual or increase tumor cell sensitivity to an existing situation. The tumor cells injected into young, normal ani-
P.V. Woolley (ed.), Cancer management in Man: Biological Response Modifiers, Chemotherapy, Antibiotics, Hyperthermia, Supporting Measures
© 1989. Kluwer Academic Publishers, Dordrecht. ISBN-13: 978-94-010-6983-0