Table Of ContentRecent Results 110
in Cancer Research
Founding Editor
P. Rentchnick, Geneva
Managing Editors
Ch. Heifarth, Heidelberg· H. J. Senn, St. Gallen
Associate Editors
M. Baum, London . V. Diehl, Koln
C. von Essen, Villigen . E. Grundmann, Munster
W Hitzig, Zurich . M. F. Rajewsky, Essen
Recent Results in Cancer Research
Volume 100: Therapeutic Strategies in Primary and
Metastatic Liver Cancer
Edited by Ch. Herfarth, P. Schlag, P. Hohenberger
1986. 163 figures, 104 tables. ISBN 3-540-16011-6
Volume 101: Locoregional High-Frequency Hyperthermia
and Temperature Measurement
Edited by G. Bruggmoser, W. Hinkelbein, R. Engelhardt,
M. Wannenmacher
1986.96 figures, 8 tables. IX, 143. ISBN 3-540-15501-5
Volume 102: Epidemiology of Malignant Melanoma
Edited by R. P. Gallagher
1986.15 figures, 70 tables. IX, 169. ISBN 3-540-16020-5
Volume 103: Preoperative (Neoadjuvant) Chemotherapy
Edited by J. Ragaz, P. R. Band, J. H. Goldie
1986. 58 figures, 49 tables. IX, 162. ISBN 3-540-16129-5
Volume 104: Hyperthermia and the Therapy of Malignant Tumors
Edited by C. Streffer
1987.52 figures, 63 tables. IX, 207. ISBN 3-540-17250-5
Volume 105: Breast Cancer
Edited by S. Brunner and B. Langfeldt
1987.59 figures, 43 tables. IX, 132. ISBN 3-540-17301-3
Volume 106: Minimal Neoplasia
Edited by E. Grundmann and L. Beck
1988.128 figures, 61 tables. IX, 194. ISBN 3-540-18455-4
Volume 107: Application of Hyperthermia
in the Treatment of Cancer
Edited by R. D. IsseIs and W. Wilmanns
1988. 118 figures, 56 tables. XII, 277. ISBN 3-540-18486-4
Volume 108: Supportive Care in Cancer Patients
Edited by H.-J. Senn and L. Schmid
1988.62 figures, 97 tables. ISBN 3-540-17150-9
Volume 109: Preclinical Hyperthermia
Edited by W. Hinkelbein, G. Bruggmoser, R. Engelhardt
1988.182 figures, 40 tables. ISBN 3-540-18487-2
P. Schlag P. Hohenberger
U. Metzger (Eds.)
Combined
Modality Therapy
of Gastrointestinal
Tract Cancer
With 105 Figures and 122 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Professor Dr. Peter Schlag
Dr. Peter Hohenberger
Chirurgische Klinik, Klinikum der UniversitiH Heidelberg
1m Neuenheimer Feld 110,6900 Heidelberg, FRG
PriV. Doz. Dr. Urs Metzger
Departement Chirurgie, Universitatsspital Zi.irich
RamistraBe 100, 8091 Zi.irich, Switzerland
ISBN-13: 978-3-642-83295-6 e-ISBN-13: 978-3-642-83293-2
DOl: 10.1007/978-3-642-83293-2
Library of Congress Cataloging-in-Publication Data
Combined modality therapy of gastrointestinal tract cancerl
P. Schlag, P. Hohenberger, U. Metzger (eds.)
p. cm. - (Recent results in cancer research; 110)
Includes index.
ISBN 0-587-18610-7 (U.S.):
1. Gastrointestinal system - Cancer - Adjuvant treatment.
I. Schlag, P. (Peter), 1948- . II. Hohenberger, P. (Peter),
1953- . III. Metzger, U. (Urs), 1945- . IV. Series.
[DNLM: 1. Combined Modality Therapy. 2. Gastrointestinal
Neoplasms - therapy. WI RE106P v. 110 1 WI 149 C731]
RC261.R35 vol. 110 [RC271.A35] 616.99'4 s - dc 19
[616.99'406] DNLM/DLC 88-4517
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© Springer-Verlag Berlin Heidelberg 1988
Softcover reprint of the hardcover 15t edition 1988
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Foreword
Modern surgical oncology is characterized by multimodal
therapy. In recent years numerous therapeutic approaches of
pre-, peri-, intra- and postoperative treatment have been in
vestigated with regard to their use in combination with surgi
cal intervention.
It now is time to analyze and to define the state of our
knowledge. For tumors of the gastrointestinal tract there are
several encouraging therapeutic approaches, such as preop
erative chemotherapy in esophageal and perioperative
chemotherapy in colon cancer. For some special tumors, like
anal carcinoma, we have clearly defined combined therapies
which even now must be viewed as standard treatment.
It is also time to demonstrate the results of several clini
cal studies that have been conducted within the last few
years that combined surgical efforts with pre- or postinter
ventional chemotherapy or radiotherapy. It is necessary to
evaluate whether these trials contribute to progress in onco
logical therapy.
The editors of this volume - surgeons at the university
hospitals of Heidelberg and Zurich - must be given the mer
it of achieving these goals. It was especially appropriate for
the Department of Surgery in Heidelberg, in close coopera
tion with the Comprehensive Cancer Center Heidelberg/
Mannheim, to prepare a review of our present knowledge of
surgical oncology as it is in the tradition of attempting to
combine different therapeutic approaches to cancer therapy.
Surgeon Vincenz Czerny was the first to found an institute
for cancer research and therapy, in 1906 in Heidelberg. At
this time two similar hospitals were already in existence, the
VI Foreword
Roswell Park Memorial Institute in Buffalo (USA) and the
Morosoff Clinic in Moskow. And it was the surgeon
K. H. Bauer from Heidelberg who established the German
Cancer Research Center in 1962. Thus the Gastrointestinal
Tract Cancer Cooperative Group of the EORTC discussed
their experiences in a location that represents both a long
tradition and an awareness of our responsibility.
Ch. Herfarth
Professor of Surgery
Head, Department of Surgery
University of Heidelberg
Director, Comprehensive Cancer Center
Heidelberg/Mannheim
Preface
The EORTC (European Organization for Research and Treatment
of Cancer) Gastrointestinal Tract Cancer Cooperative Group,
founded in 1972, is devoted to clinical research in the combined
modality treatment of gastrointestinal tract cancer. To date, the
group has conducted 30 multicenter clinical trials, 13 of which
have been completed and reported in various cancer journals. Five
studies are closed to patient entry but follow-up still continues, and
12 trials are currently open to patient entry. More than 3500 pat
ients have been entered so far in these studies with an annual entry
rate of 300-350 patients.
Why collaborative research in oncology? Collaborative research
is needed when a problem is too big to be tackled or solved by a
single center. Many problems in oncology are so difficult that the
simple rule of "two know more than one" or "two can do more
than one" certainly applies. Individual medical centers are domi
nated by one or a few outstanding people, which tends to narrow
one's vision and precludes the emergence of alternative ideas. Mul
ticenter collaboration promotes the comparison of different view
points, which is a condition for progress. Apart from the intellectu
al aspects there is the obvious advantage of pooling resources and
facilities. Even if a single center is sufficiently large to perform its
own study, the results which emerge after several years have to be
repeated by other centers before they can be generally accepted. In
publication policy, there is an obvious bias to select and publish
positive results. In cancer treatment, however, negative results may
be of similar clinical value and it is obvious that multicenter trials
are more suitable for sharing the risk of producing and publishing
negative results.
Beside the regular semiannual meetings, the EORTC Gastroin
testinal Tract Cancer Cooperative Group organizes review sessions
every 3 years, where up to date information is given on the differ
ent aspects of combined modality treatment in gastrointestinal tract
VIIJ Preface
cancer. Analysis of the current EORTC trials is supplemented by
state-of-the-art lectures from extramural experts.
This volume summarizes selected papers, which were presented
during the recent EORTC-GI Group Conference in Heidelberg.
The editor's wish is to give a topical survey on pre-, peri- and post
operative chemotherapy and radiotherapy, both in the adjuvant sit
uation and for the treatment of advanced disease. In addition, new
preclinical and experimental data relevant to the clinical situation
are included.
Hopefully, this volume will further stimulate preclinical and
clinical research in the treatment of the most common solid malig
nancy, the gastrointestinal tract tumor. Through combined efforts,
surgeons, radiotherapists, and medical oncologists will achieve
progress step-by-step.
Heidelberg/Zurich, February 1988 P.Schlag
P. Hohenberger
U.Metzger
Contents
Combined Therapy in Esophageal Cancer ...... . 1
M. Gignoux, A. Roussel, B. Paillot, M. Gillet, P. Schlag,
O. Dalesio, M. Buyse, and N. Duez
The Value of Preoperative Radiotherapy in
Esophageal Cancer: Results of a Study by the EORTC 1
P. Schlag, R. Herrmann, U. Raeth, B. Lehner, V. Schwarz,
and C. Herfarth
Preoperative (Neoadjuvant) Chemotherapy in
Squamous Cell Cancer of the Esophagus . . . . . . . . . . .. 14
A. Roussel, J. H. Jacob, P. Haegele, G. M. Jung, B. Paillot,
J. P. Heintz, M. Gignoux, S. Nasca, A. Namer, H. Bleiberg,
M. Buyse, O. Dalesio, and N. Duez
Controlled Clinical Trial for the Treatment of Patients
with Inoperable Esophageal Carcinoma: A Study of the
EORTC Gastrointestinal Tract Cancer Cooperative Group .. 21
A.Roth
Combination of Chemotherapy and Irradiation:
A New Approach in the Treatment of Locally Advanced
Esophageal Cancer . . . . . . . . . . . . . . . . . . . . . . .. 30
Combined Therapy in Gastric Cancer . . . . . . . . . . . . . .. 36
M. Lise, D. Nitti, M. Buyse, G. Cartei, A. Fornasiero,
J. Guimaraes dos Santos, and N. Duez
Phase-III Clinical Trial of Adjuvant FAM2 (5-FU, Adriamycin
and Mitomycin C) vs Control in Resectable Gastric Cancer:
A Study of the EORTC Gastrointestinal Tract Cancer
Cooperative Group . . . . . . . . . . . . . . . . . . . . . . .. 36
X Contents
R. Jakesz, C. Dittrich, J. Funovics, F. Hofbauer, H. Rainer,
G. Reiner, M. Schemper, R. Schiessel, and M. Starlinger
The Effect of Adjuvant Chemotherapy in Gastric Carcinoma
Is Dependent on Tumor Histology: 5-Year Results
of a Prospective Randomized Trial . . . . . . . . . . . . . . .. 44
E. Gez, A. Sulkes, T. Peretz, and Z. Weshler
Combined 5-Fluorouracil and Radiation Therapy
Following Resection of Locally Advanced Gastric Carcinoma:
A 5-Year Follow-Up. . . . . . . . . . . . . . . . . . . . . . .. 52
J. W L. Fielding
The Value of a Multidisciplinary Approach
in the Management of Gastric Cancer . . . . . . . . . .. 57
The Approach to Hepatobiliary-Pancreatic Cancer. ..... 65
R. Pichlmayr, B. Ringe, W O. Bechstein, W Lauchart,
and P Neuhaus
Approach to Primary Liver Cancer. . . . . . . . . .. .... 65
S.Bengmark
Biliary Duct Cancer: Therapeutic Nihilism or Prospect .. 74
F. P Gall and F. Kockerling
The Problem of Radical Surgery in Pancreatic Cancer and
Its Implications for a Combined-Treatment Approach . .. . 79
J.A. Wils
Treatment of Pancreatic Carcinoma: Therapeutic Nihilism? . 87
Combined Therapy in Colorectal Cancer . . . . . . . . . . .. 95
V.Metzger
Adjuvant Portal Infusion Chemotherapy in Colorectal Cancer 95
J. PArnaud, M. Buyse, M.Adloff, B. Nordlinger, J. C. Pector,
and N.Duez
Interim Analysis of a Double-Blind Phase-III Clinical Trial
of Adjuvant Levamisole Versus Control in Resectable
Dukes-C Colon Cancer: A Study of the EORTC
Gastrointestinal Tract Cancer Cooperative Group . . . . 101
R.D.James
The Northwest of England Rectal Cancer Trial .. 104
W Niebel, V. Schulz, M. Ried, J. Erhard, F. Beersiek, G. Blocher,
H. Nier, H. Halama, E. Scherer, G. Zeller, and F. W Eigler
Five-Year Results of a Prospective and Randomized Study:
Experience with Combined Radiotherapy and
Surgery of Primary Rectal Carcinoma . . . . . . . . . . . . . . 111
