Cancer Chemotherapy and Selective Drug Development: Proceedings of the 10th Anniversary Meeting of the Coordinating Committee for Human Tumour Investigations, Brighton, England, October 24–28, 1983

535 Pages·1984·16.07 MB·English

by  J. M. A. Whitehouse (auth.)

CANCER CHEMOTHERAPY AND
SELECTIVE DRUG DEVELOPMENT
DEVELOPMENTS IN ONCOLOGY
F.J. Cleton and J.W.I.M. Simons, eds.: Genetic Origins of Tumour Cells. 90-247-2272-1.
J. Aisner and P. Chang, eds.: Cancer Treatment Research. 90-247-2358-2.
B.W. Ongerboer de Visser, D.A. Bosch and W.M.H. van Woerkom-Eykenboom, eds.:
Neuro-oncology: Clinical and Experimental Aspects. 90-247-2421-X.
K. Hellmann, P. Hilgard and S. Eccles, eds.: Metastasis: Clinical and Experimental Aspects.
90-247-2424-4.
H.F. Seigler, ed.: Clinical Management of Melanoma. 90-247-2584-4.
P. Correa and W. Haenszel, eds.: Epidemiology of Cancer of the Digestive Tract.
90-247-2601-8.
L.A. Liotta and I.R. Hart, eds.: Tumour Invasion and Metastasis. 90-247-2611-5.
J. Banoczy, ed.: Oral Leukoplakia. 90-247-2655-7.
C. Tijssen, M. Halprin and L. Endtz, eds.: Familial Brain Tumours. 90-247-2691-3.
F.M. Muggia, C.W. Young and S.K. Carter, eds.: Anthracycline Antibiotics in Cancer.
90-247-2711-1.
B.W. Hancock, ed.: Assessment of Tumour Response. 90-247-2712-X.
D.E. Peterson, ed.: Oral Complications of Cancer Chemotherapy. 0-89838-563-6.
R. Mastrangelo, D.G. Poplack and R. Riccardi, eds.: Central Nervous System Leukemia.
Prevention and Treatment. 0-89838-570-9.
A. Polliack, ed.: Human Leukemias. Cytochemical and Ultrastructural Techniques in
Diagnosis and Research. 0-89838-585-7.
W. Davis, C. Maltoni and S. Tanneberger, eds.: The Control of Tumor Growth and its
Biological Bases. 0-89838-603-9.
A.P.M. Heintz, C. Th. Griffiths and J.B. Trimbos, eds.: Surgery in Gynecological Oncology.
0-89838-604-7.
M.P. Hacker, E.B. Double and I. Krakoff, eds.: Platinum Coordination Complexes in
Cancer Chemotherapy. 0-89838-619-5.
M.J. van Zwieten. The Rat as Animal Model in Breast Cancer Research: A Histopathological
Study of Radiation- and Hormone-Induced Rat Mammary Tumors. 0-89838-624-1.
B. Lowenberg and A. Hogenbeck, eds.: Minimal Residual Disease in Acute Leukemia.
0-89838-630-6.
I. van der Waal and G.B. Snow, eds.: Oral Oncology. 0-89838-631-4.
B. W. Hancock and A.M. Ward, eds.: Immunological Aspects of Cancer. 0-89838-664-0.
K. V. Honn and B.F. Sloane. Hemostatic Mechanisms and Metastasis. 0-89838-667-5.
CANCER CHEMOTHERAPY AND
SELECTIVE DRUG DEVELOPMENT
Proceedings of the 10th Anniversary Meeting of the
Coordinating Committee for Human Tumour Investigations,
Brighton, Eng/and, October 24-28, 1983
edited by
K.R. Harrap
W. Davis
A.H. Calvert
Technical Editor: A.S. Robinson
"
~
Martinus Nijhoff Publishing
a member of the Kluwer Academic Publishers Group
Boston/The Hague/Dordrecht/Lancaster
Distributors for North America:
Kluwer Academic Publishers
190 Old Derby Street
Hingham, MA 02043
Distributors for all other countries:
Kluwer Academic Publishers Group
Distribution Centre
P.O. Box 322
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The Netherlands
Library of Congress Cataloging in Publication Data
Main entry under title:
Cancer chemotherapy and selective drug development.
(Developments in onology)
Includes bibliographies and indexes.
1. Cancer--Chemotherapy--Congresses. 2. Anti
neoplastic agents--Testing--Congresses. I. Harrap,
K. R. II. Davis, Walter. III. Calvert, A. Hilary.
IV. Co-ordinating Committee for Human Tumour
Investigations. V. Series. [DNLM: 1. Antineoplastic
Agents--therapeutic use--congresses. 2. Neoplasms--
drug therapy--congresses. W1 DE998N / QZ 267 C2105 1983J
RC271.C5C3135 1984 616.99'4061 84-14677
ISBN-13: 978-1-4613-3839-0 e-ISBN-13: 978-1-4613-3837-6
001: 10.1007/978-1-4613-3837-6
Copyright 1984 © by Martinus Nijhoff Publishing, Boston
Softcover reprint of the hardcover lst edition 1984
All rights reserved. No part of this publication may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, mechanical, photocopy
ing, recording, or otherwise, without written permission of the publisher, Martinus
Nijhoff Publishing, 190 Old Derby Street, Hingham, Massachusetts 02043.
PREFACE
Over the past 30 years many significant advances have been made in the
management of a number of disseminated malignant diseases. The prognosis for
diseases such as childhood leukaemia, choriocarcinoma and Hodgkin's disease
has gradually been transformed as better anti tumour agents have become
available and their clinical use has been refined. During the past 10 years
the advent of new agents, particularly cisplatin, bleomycin and the
podophyllotoxins, has allowed the cure of disseminated testicular tumours.
This degree of success has not, however, been achieved in the case of a number
of other common cancers. Ovarian carcinoma is tantalisingly chemo-sensitive
and although there are long term survivors from disseminated disease, these
are only a small proportion of the total. Breast cancer, although "sensitive"
to a multitude of drugs appears to have yielded neither survival benefit, nor
cure to the efforts of therapists, while tumours such as those of the colon
remain stubbornly unresponsive.
Against this backcloth it is apparent that additional more selective
treatments are needed if further impact is to be made on the problem of
cancer. The development of such agents requires the integration of a
multidisciplinary effort encompassing the fields of chemistry, biology and
medicine.
This symposium provided a forum for clinical and preclinical sCientists,
where current aspects of cancer treatment were reviewed and approaches to the
development of a new generation of more selective anticancer drugs discussed.
THE EDITORS
CONTENTS
PREFACE
by The Editors v
LIST OF CONTRIBUTORS .................................................. . xvii
CHAPTER I: ADVANCES IN CANCER TREATMENT
1. NEW APPROACHES TO OLD PROBLEMS
Clinical drug resistance
by J.M.A. Whitehouse ................................................. . 5
New therapies with old drugs
by I.E. Smith ............................................................ . 13
Antimetabolite combinations possessing enhanced efficacy
by M.H.N .. Tattersall .............................................. ,. 19
Mismatched bone marrow transplantation
by R.L. Powles, G. Goss, A. Pedrazzini, M. Crofts, H. Clink,
J. Millar, B. Khan and D. Perez •••••••••••••••••••••••••••••••• 33
Prospects for immunotherapy
by P. Alexander ...................................................... . 43
2. CURRENT CLINICAL PROGRESS WITH NEW AGENTS
Platinum analogs
by S.K. Carter .................................................. , ••••• 49
Mitoxantrone: A promising new agent for the treatment of human
cancer
by C.P. Turnbull and D. Jackson ••••••••••••••••••••••••••.••••• 55
Current clinical progress - podophyllotoxins
by B. F. Issell .................................................. , ..... . 65
Pharmacology of nitrosourea anticancer agents
by A.L. Wang and P.S. Schein ••••••••••••••••••••••••••••••••••• 71
Current clinical progress with new agents: alkylating agents
by S.. Eckhard t ........................................................................... . 77
Interferon
by J. L. Toy .............................................................................. . 83
vii
viii
3. DRUG TREATMENT OF SPECIFIC CANCERS
Chemotherapy of lung cancer
by H.H. Hansen.................................................................................................. 91
Hormone-chemotherapy in treatment of advanced breast cancer
by F., Cavalli, A. Goldhirsch, R. Joss and K. W. Brunner ••••••••• 95
Chemotherapy of ovarian cancer
by E.. Wil thshaw ................................................................................................ 10-5
Obstacles to improved end-results in head and neck cancer
byR.E. Wittes ....•.••.•.••••••.••...••••..•..•••••.••••....•.• 111
Treatment of disseminated malignant lymphoma
by T.A. Lister and HI'S. Dhaliwal............................... 117
Malignant disease in childhood
by M.G Matt........................................................................................................ 123
Chemotherapy of disseminated testicular cancer
by L.H. Einhorn............................................................................................... 135
Rational approach to the management of febrile granulocytopenic
patients
by H. Lagast and J. Klastersky ••••••••••••••••••••••••••••••••• 141
CHAPTER II: CONTROL OF PAIN AND VOMITING IN CANCER PATIENTS
Effective use of narcotic analgesics
by R.G. Twycross .............................................................................................. 147
A double-blind cross-over study of two oral formulations of
morphine
by J. Welsh, J.F.B. Stuart, T. Haveshaw, P. Billiaert and
K. C. CaIman ................................................................................................. 153
Non-narcotics and co-analgesics
by G.W. Hanks.................................................................... 159
Advanced cancer: Oncologist, family doctor or hospice?
by F.. Randall ................................................................................... 165
Why do cancer patients vomit?
by G. . W.. Hanks ............................................................................................ 173
Cancer, vomiting and gut motility
by C. . L.. 3mi th .............. "................................................................................. 177
The medical management of malignant bowel obstruction
by M. . J.. Baines ............................................................................. 182
Etiology of chemotherapy-induced vomiting
by A. L. Harris ................................................................................. 189
ix
The management of nausea and vomiting caused by anticancer
chemotherapy
by C.J. Williams............................................................................................ 195
CHAPTER III: PERSPECTIVES IN NEW DRUG DEVELOPMENT
1. PROBLEMS IN ACHIEVING DRUG SELECTIVITY
Experimental models and their predictive value in new drug
development: A critical appraisal: I. Toxicity models
by A. Goldin and P.S. Schein ••••••••••••••••••••••••••••••••••• 209
In vivo anti tumour models and drug development
by A.E. Bogden, J.M. Venditti and W.R. Cobb •••••••••••••••••••• 215
Assays for clonogenic human tumour cells in experimental and
clinical chemotherapy
by G.G. Steel, V.D. Courtenay and R.R. Sandhu •••••••••••••••••• 221
Mechanisms of resistance to anticancer agents
by B .. W.. Fox ........................................................................................................ 227
The role of pharmacokinetics in drug design and use
by J .. G.. Me Vie ...................................... It .......................... It It It It .. It .. It It It .... It It It It It 231
Novel structures in development
by V L Narayanan .. 235
It It It It It It It It It It It .. It It It ...... It It It .... It It It It .. It It It It It It It It It It It It .. It It It It .. It
Hypoxia-mediated drugs for radio- and chemotherapy
by G.E. Adams, I.J. Stratford and P.W. Sheldon ••••••••••••••••• 241
2. TARGETTED CHEMOTHERAPY
Induction of cell differentiation as a target for cancer therapy
by A. Bloch .. 251
It It ........ It It ........ It It It .. It .. It It .. It It .. It It .. It .. It .. It .... It It It It It It It It It It It It It .. It It It
Complement lysis of tumour cells induced by univalent antibodies
by G.T. Stevenson, V.M. Cole, M.J. Glennie and H.F. Watts •••••• 257
Antibody-toxin conjugates as anticancer agents
by P.E. Thorpe It.. 263
It .. It .. It It It It .. It It .. It It It It .. It It It It It .. It It .. It It It .... It It It It It .. It It It It It It It It It It
3. REGULATORY MOLECULES IN CHEMOTHERAPY
Biological response modifiers as anticancer agents
by R.K. Oldham ...... 271
It .... It It It .... It It It ........ It It It It It It It ...... It .... It It It •• It It It It .. It .. It ...... " It
Prostaglandins and cancer - therapeutic potential
by Tit J.. Powles ••••••••.••••..•••••••••.•••••••..•••••••.•.••••• 277
The therapeutic potential of lymphokines in human cancer
by D.C. Dumonde •••••••••••••••••••••••••••••••••••••••••••••••• 283
x
The interleukins 289
by R.J. Booth, R.L. Prestidge and J.D. Watson ••••••••••••••••••
The role of polyamines in cell differentiation 295
by P.K. Bondy, J.L. Ryan and Z.N. Canellakis •••••••••••••••••••
Polyamines, immune response and tumour growth control 301
by W.A. Boggust, S. O'Connell and A. Drumm •••••••••••••••••••••
Potential use of retinoids in cancer prevention and treatment 307
by G.J.S. Rustin •••••••••••••••••••••••••••••••••••••••••••••••
CHAPTER IV: DESIGN AND DEVELOPMENT OF NEW DRUGS
Inosine 5'-phosphate dehydrogenase as a target for cancer
chemotherapy.
by T.J. Boritzki, D.W. Fry, J. Besserer, P.D. Cook and
R.C. Jackson"""""""""""""""""""""""""""""""""""""""""""""""" .... " 315
Antitumour activity and pharmacology of CCRG 81010
by J.A. Hickman and M.F.G. Stevens ••••••••••••••••••••••••••••• 321
New pyrimidine nucleosides with potent antiviral activity
by B. Leyland-Jones """" .. """""""""""""""""""."""" .. """""""""""""" 327
Lipophilic inhibitors of dihydrofolate reductase
by C.A. Nichol, C.W. Sigel and D.S. Duch ••••••••••••••••••••••• 333
Review of phase I-II clinical trials with vinzolidine (VZL),
a new orally active semisynthetic vinblastine derivative
by R.L. Nelson ••••••••••••••••••••••••••••••••••••••••••••••••• 339
New developments in anthracyclines
by A. Di Marco, A.M. Casazza and T. Facchinetti •••••••••••••••• 345
Nitrosoureas - still a challenge for developmental cancer
chemotherapy
by G. Eisenbrand "" .. """"""""""" .. """ .. """""""""""""" .. """""""""""".. 351
Further objectives in the development of platinum drugs
by M.J. Cleare ••••••••••••••••••••••••••••••••••••••••••••••••• 357
CHAPTER V: CHROMATIN AS A TARGET IN CANCER CHEMOTHERAPY
The structure of active genes and HMG proteins in normal and
transformed cells
by G.H. Goodwin """""""""""""""""""""""""""""""""""."" .. """"".""" 365
Pretreatment of human colon tumour cells with DNA methylating
agents inhibits their ability to prevent chloroethylnitrosourea
induced DNA interstrand crosslinking
by L.C. Erickson, C. Zlotogorski and N.W. Gibson ••••••••••••••• 371
xl
Structural requirements for DNA intercalation and their
relevance to drug design
by M.J. Waring, K.R. Fox and S. Haylock 377
Dialkanesulphonates and chromatin
by B.W. Fox, P. Bedford and J. Hartley 383
DNA repair characteristics of Walker rat carcinoma cells
sensitive and resistant to cis-diamminedichloroplatinum(II)
(cisplatin) and difunctional alkylating agents
by J.J. Roberts, C.J. Rawlings and F. Friedlos ••••••••••••••••• 389
Is alkylating agent "priming" a DNA repair phenomenon?
by J.L. Millar, B.C. Millar, M. Tilby and B.D. Evans ••••••••••• 395
DTIC induces damage in melanoma DNA during semi-conservative DNA
synthesis
by U. L6nn and S. L6nn 401
The non-random binding of chlorambucil to DNA in chromatin
by A. Jeney, K.R. Harrap and R.M. Orr •••••••••••••••••••••••••• 407
Alkylating antitumour agents decrease histone acetylation in
Ehrlich ascites tumour cells
by H. Grunicke, H. Zwierzina, A. Loidl, W. HeIliger and
B. Puschendorf ••••••••••••••••••••.••••••...••...••••••••••••.• 413
Influence of the nuclear matrix on nuclear structure and
response to anticancer drugs
by K.D. Tew •••••••••••••••••••••••••••••••••••••••••••••••••••• 419
Cytotoxicity of a steroid-linked mustard (Estramustine) through
non-DNA targets
by B. Hartley-Asp ..•••..•.••••••.•...••••....••.•.••.•••••.•..• 425
Potentiation of cytotoxicity by inhibitors of nuclear
ADP-ribosyl transferase
by S. Shall •••••••••••••••••••••••••••••.••••••••••••••••••••••• 431
CHAPTER VI: ENDOCRINE THERAPY
Adjuvant tamoxifen treatment in operable breast cancer. Should
the treatment continue for many years?
by A. Wallgren, K. Idestr6m, U. Glas, M. Kaigas, N-O. Theve,
N. Wilking, L. Karnstr6m, L. Skoog and B. Nordenskj6ld ••••••••• 439
Adjuvant hormonal therapy of breast cancer
by H.A. de Haan and J. Diver ••••••••••••••••••••••••••••••••••• 445
New approaches to the use of endocrine therapy in breast cancer
by R.C. Coombes, J. Williams, A. Brodie, T.J. Powles and
A.M. Neville ••••••••••••••••••••••••••••••••••••••••••••••••••• 451
The pharmacology of a new antiestrogen
by J.A. Clemens, L.J. Black and R.L. Zerbe ••••••••••••••••••••• 457