Cancer Therapy: Monoclonal Antibodies, Lymphokines New Developments in Surgical Oncology and Chemo- and Hormonal Therapy

314 Pages·1989·7.09 MB·English

by  R. A. Reisfeld

H. G. Beger M. Buchler
R. A. Reisfeld G. Schulz
(Eds.)
Cancer Therapy
Monoclonal Antibodies, Lymphokines
New Developrrzents in Surgical Oncology
and Chemo- and Hormonal Therapy
With the Editorial Collaboration of
B. Greifenberg, Marburg and K. H. Link, VIm
With 94 Figures and 92 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Dr. Hans G.Beger, FACS
Professor of Surgery
Dr. Markus Buchler
Lecturer in Surgery
Department of General Surgery
University of Ulm
SteinhOvelstraI3e 9, 7900 Ulm, FRG
Dr. Ralph A. Reisfeld
Division of Tumor Cell Biology
Scripps Clinic & Research Foundation
10666 North Torrey Pines Road, La Jolla, CA 92037, USA
Priv. Doz. Dr. Gregor Schulz
Clinical Research
Behringwerke AG Marburg
P.O. Box 1140, 3550 Marburg, FRG
ISBN-13:978-3-642-73723-7 e-ISBN-13:978-3-642-73721-3
DOl: 10.1007/978-3-642-73721-3
Library of Congress Cataloging·in·Publication Data
Cancer therapy : monoclonal antibodies, Iymphokines : new developments in surgical
oncology and chemo· and hormonal therapy 1 H.G.Beger ... let aL], (eds.) ; in
collaboration with B. Greifenberg. p. em. Includes bibliographies and index.
ISBN-I3:978-3-642-73723-7 (U. S.)
1. Cancer--Treatment. 2. Antibodies, Monoclonal--Therapeutic use. 3. Lymphokines--Thera
peutic use. 4.Cancer--Surgery. 5.Cancer--Hormone therapy. 6.Cancer--Chemotherapy.
7.Beger, H.G. (Hans G.) I. Greifenberg, B.
IDNLM: 1. Antibodies, Monoclonal--therapeutic use. 2. Antineoplastic Agents--therapeutic
use. 3. Hormones-therapeutic use. 4. Lymphokines--therapeutic use. 5. Neoplasms--drug
therapy. 6. Neoplasms--surgery. QZ 266 C2172] RC270.8.C373 1988
616.99'406--dc19 DNLM/DLC 88-29509
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Preface
The recent development of new strategies in cancer therapy was
the main topic of an international meeting which took place at Rei
sensburg Castle in February, 1988. Here, experts in the field of tu
mor immunology, surgical oncology, and cancer chemotherapy dis
cussed future directions in cancer treatment.
In 1975, Kohler and Milstein first described the technique of cell
hybridization, which is used to produce monoclonal antibody
(MoAb) reagents for the detection of tumor markers in sera, the in
vitro analysis of leukemia or the histologic differential diagnosis of
malignancies as opposed to chronic infectious diseases. Recently, it
has been demonstrated that radiolabelled murine MoAbs are ex
cellent tools for the in vivo localization of tumors. Meanwhile, ini
tial clinical experience with the therapeutical use of MoAbs has
been gained which shows that the latter either mediate cytotoxic
functions, such as antibody-dependent cellular cytotoxicity or
complement-dependent cytotoxicity, or are effective in conjugation
with radionuclides, cytostatics, or toxins. New modifications, such
as the "humanization" of murine antibodies, which will improve
the efficacy of the above-mentioned therapy, are discussed in this
volume.
Recent advances in DNA technology have resulted in the produc
tion of a number of recombinant glycoproteins, for example, in
terferons or tumor necrosis factor, which directly inhibit tumor
growth. Other immune response modifiers, such as interleukin-2
(IL-2) or the colony-stimulating factors (CSFs), which are able to
enhance proliferation and activity of T-Iymphocytes or other he
matopoietic cells, are now clinically available. Stimulated "killer
lymphocytes" or macrophages are powerful "tumor killers", as has
been demonstrated by clinical studies using recombinant IL-2,
GM-CSF, or G-CSF. In addition, hematopoietic growth factors are
able to accelerate regeneration of blood cells following chemother
apy. Initial clinical experience with GM-CSF and G-CSF has
shown that severe neutropenia may be prevented or at least decel
erated, which then results in a reduced number of severe infec
tions. Other CSFs, such as interleukin 3 or erythropoietin, induce
speedier reconstitution of platelets or erythrocytes. Thus, the clini
cal application of recombinant hematopoietic growth factors will
VI Preface
not only improve tolerability of chemotherapy, but may also allow
the administration of higher doses of cytostatics, thus resulting in
better response rates.
The approach of regional chemotherapy combined with new tech
niques of surgical oncology, including isolated regional hyperther
mal perfusion and chemoembolization of tumors, presents a new
concept of cancer treatment. Several randomized trials now exist
which demonstrate a higher response rate following intrahepatic
infusion rather than systemic infusion in the treatment of hepatic
metastases from colorectal carcinoma. The results of regional
chemotherapy of the liver from different research institutions are
presented in this volume, the success rates pointing to the promis
ing role of regional cancer treatment in the future.
In some malignancies, e. g., lymphoblastic leukemia, testicular can
cer, and Hodgkin's disease, a high frequency of long-term cure
rates has been achieved by the introduction of new chemothera
peutic regimens. However, patients with some of the most common
cancers, for instance, lung cancer, colorectal cancer, or pancreatic
cancer, still have a poor chance of survival if the tumor cannot be
removed by surgery.
We hope that the various new strategies in cancer treatment pre
sented in this book will help to point out that only combined re
search efforts in various fields of cancer treatment will result in im
proved therapy of malignancies.
December 1988 H. G. Beger M. Buchler
R. A. Reisfeld G. Schulz
Contents
Monoclonal Antibodies ........... . 1
R. A. REISFELD, B. MULLER, and H.-M. YANG
Immunochemotherapy of Cancer: A Perspective 3
K. BOSSLET, A. STEINSTRASSER, A. SCHWARZ, H. P. HARTH US,
G. LUBEN, L. KUHLMANN, and H. H. SEDLACEK
Quantitative Considerations Supporting the Irrelevance of
Circulating Serum Carcinoembryonic Antigen for the
Immunoscintigraphic Visualization of Carcinoembryonic
Antigen-Expressing Carcinomas . . . . . . . . . . . . . . . 10
H.KALOFONOS and A.A. EPENETOS
Radioimmunotherapy with Iodine 131-Labelled Antibodies in
Ovarian, Colonic and Brain Tumours . . . . . . . . . . . .. 18
A. PLANTING, J. VERWEIJ, P. COX, M. PILLA Y, and G. STOTER
Radioimmunodetection and Radioimmunotherapy in
Myosarcoma . . . . . . . . . . . . . . . . . . . . . . . . 27
M.BUCHLER, R.KUBEL, R.KLAPDOR, K.-H.MUHRER,
H. FRIESS, B. LORENZ, G. SCHULZ, K. BOSSLET, and H. G. BEGER
Immunotherapy of Pancreatic Cancer with Monoclonal
Antibody BW 494: Results from a Multicentric Phase I-II
Trial. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32
H. MELLSTEDT, J.-E. FRODIN, G. MASUCCI, C. LINDEMALM,
C. WEDELIN, B. CHRISTENSSON, J. SHETYE, P. BIBERFELD,
A.-K. LEFVERT, P. PIHLSTEDT, J. MAKOWER, U. HARMENBERG,
B. WAHREN, B. AHLMAN, B. CEDERMARK, R. ERWALD,
I. MAGNUSSON, J.NATHANSSON, and A.RIEGER
Mab 17-1 A Used for Therapy of Patients with Metastatic
Colorectal Carcinomas . . . . . . . . . . . . . . . . . . .. 42
W. G. DIPPOLD and K.-H. MEYER ZUM BUSCHENFELDE
Immunotherapy of Malignant Melanomas ........... 51
R.KLAPDOR
Interaction of Monoclonal Antibodies with Biological
Response Modifiers and Cytostatics . . . . . . . . . . . . . ., 56
VIII Contents
Lymphokines . . .. 71
A.LINDEMANN, F.HERRMANN, H.GAMM, W.OSTER, and
R. MERTELSMANN
Cancer Treatment with Cytokines: Concepts and First Clinical
Experience . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73
M. S. MITCHELL
Low-dose Cyclophosphamide and IL-2 in the Treatment of
Advanced Melanoma . . . . . . . . . . . . . . . . . . . 85
A.GANSER, B.VOLKERS, J.GREHER, F.WALTHER, and
D.HOELZER
Application of Granulocyte-Macrophage Colony-Stimulating
Factor in Patients with Malignant Hematological Diseases 90
H. LINK, M. FREUND, H. KIRCHNER, M. STOLL, H. SCHMID,
P. BUCSKY, J. SEIDEL, G. SCHULZ, R. E. SCHMIDT, H. RIEHM,
H. POLIWODA, and K. WELTE
Enhancement of Autologous Bone Marrow Transplantation
with Recombinant Human Granulocyte-Macrophage
Colony-Stimulating Factor (rhGM-CSF) ........ . 96
R.G.STEIS, J.CLARK, D.L.LONGO, J.SMITH, R.MILLER,
F. RUSCETTI, J. HURSEY, and W. URBA
A Phase Ib Evaluation of Recombinant Human
Granulocyte-Macrophage Colony-Stimulating Factor ..... 103
N. NIEDERLE and G. KUMMER
The Role of Interferon in the Management of Patients with
Hairy Cell Leukemia and Multiple Myeloma . . . . . . 112
F.PORZSOLT, W.DIGEL, C.BUCK, A.RAGHAVACHAR,
M.STEFANIC, and W.SCHONIGER
Possible Mechanism of Interferon Action in Hairy Cell
Leukemia. . . . . . . . . . . . . . . . . . . . . . . . . .. . 124
R. SCHIESSEL
Tumor Vaccination in the Treatment of Colorectal Cancer. . 132
New Approaches in Surgical Oncology .............. 141
R.BITTNER and H.G.BEGER
New Developments in Surgical Oncology . . 143
P.SCHLAG
Cancer Surgery - Conservative or Radical? . . 154
S.BENGMARK
Regional Chemotherapy of the Liver and Hepatic Artery
Occlusion .............................. 163
Contents IX
N.KEMENY
Regional Chemotherapy of Hepatic Metastases. 169
F. SAFI, R. BITTNER, R. ROSCHER, K. SCHUMACHER, W. GAUS,
and H.G.BEGER
Regional Chemotherapy in Hepatic Metastases of Colorectal
Carcinoma: Continuous Intra-arterial Versus Continuous
Intra-arterial/Intravenous Therapy ............... 176
K.-H.MUHRER and H.GRIMM
Isolated Regional Hyperthermal Liver Perfusion: Indications,
Technique and Results ...................... 190
K.-H. SCHULTHEIS, M. PLIESS, H.-H. GENTSCH, H. BODEKER,
C.GEBHARDT, and K.SCHWEMMLE
Chemoembolization of Liver Tumors .............. 201
S.G.BOWN
New Cancer Treatment with Lasers - Photodynamic Therapy
and Interstitial Hyperthermia ................... 216
E. KRAAS, E. LOHDE, O. ABRI, H. SCHLICKER, S. MATZKU,
H.KALTHOFF, and W.H.SCHMIEGEL
Specificity, Kinetics, and Distribution of Monoclonal
Antibodies to Carcinoembryonic Antigen in Human
Colorectal Carcinoma by Ex Vivo Human Tumor Perfusion. . 223
Chemotherapy and Hormonal Therapy . . . . . . . . . . . . . . 233
G.FALKSON
Chemotherapy: Benefits and Limits . 235
H. P. KRAEMER and H. H. SEDLACEK
The Human Tumor Clonogenic Assay for the Prediction of
Tumor Sensitivity ......................... 243
K.H.LINK
Chemosensitivity: Directed Regional Chemotherapy of Liver
Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
I. H. KRAKOFF
Clinical Development of New Anthracyclines . 259
J.VERWEIJ, E.SALEWSKI, and G.STOTER
First Clinical Experience with Cytorhodin S - The First
Compound of a New Class of Anthracyclines. . . . . . . . . . 263
B. GREIFENBERG
Pirarubicin: A New Drug in the Treatment of Malignant
Diseases ........................... .. 270
H.-H. FIEBIG, H. HENSS and H. ARNOLD
Pirarubicin - A New Anthracycline with High Activity in
Untreated Patients with Small-Cell Cancer of the Lung . . . . 280
X Contents
K.HOFFKEN
New Approaches in the Hormonal Therapy of Breast Cancer . 284
E. D. KREUSER, W. D. HETZEL, F. PORZSOLT, and R. HAUTMANN
Reproductive Toxicity with and Without Administration of
Luteinizing-Hormone-Releasing Hormone Agonist During
Adjuvant Chemotherapy in Patients with Germ Cell Tumors . 292
Subject Index ........................... 303
List of Contributors *
Abri, O. 2231 Harmenberg, U. 42
Ahlman, B. 42 Hautmann, R. 292
Arnold, H. 280 Harthus, H.P. 10
Beger, H.G. 32,143, 176 Herrmann, F. 73
Bengmark, S. 163 Hetzel, W. D. 292
Biberfeld, P. 42 Henss, H. 280
Bittner, R. 143, 176 HOffken, K. 284
BOdeker, H. 201 Hoelzer, D. 90
Bosslet, K. 10,32 Hursey, J. 103
Bown, S.G. 216 Kalofonos, H. 18
Buck, C. 124 Kalthoff, H. 223
Bucsky, P. 96 Kemeny, N. 169
Buchler, M. 32 Kirchner, H. 96
Cedermark, B. 42 Klapdor, R. 32, 56
Christensson, B. 42 Kraas, E. 223
Clark, J. 103 Kraemer, H. P. 243
Cox, P. 27 Krakoff, I. H. 259
Digel, W. 124 Kreuser, E. D. 292
Dippold, W. G. 51 Kubel, R 32
Epenetos, AA 18 Kuhlmann, L. 10
Erwald, R. 42 Kummer, G. 112
Falkson, G. 235 Lefvert, A-K. 42
Fiebig, H.-H. 280 Lindemalm, C. 42
Freund, M. 96 Lindemann, A 73
Friess, H. 32 Link, H. 96
FrOdin, J.-E. 42 Link, K. H. 249
Gamm, H. 73 LOhde, E. 223
Gaus, W. 176 Longo, D.L. 103
Ganser, A 90 Lorenz, B. 32
Gebhardt, C. 201 Luben, G. 10
Gentsch, H.-H. 201 Magnusson, I. 42
Greher, J. 90 Makower, J. 42
Greifenberg, B. 270 Masucci, G. 42
Grimm, H. 190 Matzku, S. 223
* You will find the addresses at the beginning of the respective contribution.
1 Page on which contribution begins.