Sandostatin® in the Treatment of Acromegaly: Consensus Round Table, Amsterdam 1987

167 Pages·1988·2.09 MB·English

by  M. O. Thorner

Sandostatin® in the
Treatlllent of Acrolllegaly
Consensus Round Table, Amsterdam 1987
Editor: Steven W. J. Lamberts
With 78 Figures and 37 Tables
Springer-Verlag Berlin Heidelberg New York
London Paris Tokyo
Professor Steven W. J. Lamberts, M.D.
Rotterdam, University Hospital, Dijkzigt
Dr Molewaterplein 40
3015 GD Rotterdam
The Netherlands
ISBN-13:978-3-642-73696-4 e-ISBN-13:978-3-642-73694-0
DOl: 10.1007/978-3-642-73694-0
Library of Congress Cataloging-in-Publication Data
Sandostatin® in the treatment of acromegaly.
1. Octreotide acetate-Therapeutic use-Testing-Congresses. 2. Acromegaly-Chemotherapy
Congresses. I. Lamberts, Steven W. J. [DNLM: 1. Acromegaly-drug therapy-congresses.
2. Somatostatin-analogs & derivatives-congresses. 3. Somatostatin-therapeutic use-congresses.
WK 550 S218 1987]
RC658.3.S26 1988 616.4'7 88-17620
ISBN-13 :978-3-642-73696-4 (U .S.)
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is
concerned, specifically those of translation, reprinting, reuse of illustrations, broadcasting, reproduc
tion by photocopying machine or similar means, and storage in data banks.
Under § 54 of the German Copyright Law, where copies are made for other than private use, a fee is
payable to Verwertungsgesellschaft Wort, Munich.
© Springer-Verlag, Berlin Heidelberg 1988
and Sandoz Ltd, Basle 1988
Softcover reprint of the hardcover 1st edition 1988
Product Liability: The publisher can give no guarantee for information about drug dosage and appli
cation thereof contained in this book. In every individual case the respective user must check its
accuracy by consulting other pharmaceutical literature.
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence
of a specific statement, that such names are exempt from the relevant protective laws and regulations
and therefore free for general use.
2329/3321-543210 - Printed on acid-free paper
Table of Contents
Abbreviations . . . VII R. Cozzi, D. Dallabonzana,
Authors' Addresses VIII G. Oppizzi, M. M. Petroncini 75
Nomenclature . . . X 10. Treatment of Acromegaly with the
Somatostatin Analogue
I. Clinical Aspects of Growth Hor- SMS 201-995 (Sandostatin®)
mone Hypersecretory States H.-J. Quabbe, U. PLOckinger . 81
M. O. Thorner, M. L. Hartman, II. Observations During a Clinical
M. L. Vance .......... 1 Trial of Sandostatin® in Acro-
2. Correlation Between Preoperative megalic Patients
Testing and Tumour H. (j}rskov, J. Weeke, S. E. Chris-
Morphology in Acromegaly tensen, S. Nielsen, A. Flyvbjerg,
D. Killinger, J. Gonzalez, J. O. L. J(Jrgensen, N. M(Jller,
E. Horvath, K. Kovacs, H. Smyth 9 A. G. Harris .......... 83
3. Acromegaly: Objectives of 12. Effects of Long-Term Adminis-
Therapy tration of Sandostatin® (SMS
H. -J. Quabbe ...... 17 201-995) at Increasing Doses in 40
4. Surgical Treatment of Acromegaly Acromegalic Patients. Results
A. M. Landolt, R. Illig, J. Zap! . 23 from the French Sandostatin
5. External Radiation Therapy of Acromegaly Study Group
Acromegaly G. Sassolas, P. Fossati,
J. A. H. Wass, E. Ciccarelli, P. Chanson, R. Costa, B. Estour,
S. Corsello, G. M. Besser, A. Deidier, A. G. Harris .... 89
N. Plowman, A. E. Jones 37 13. Experience with Sandostatin® in
6. Bromocriptine Treatment of Various Groups of Acromegalic
Acromegaly Patients
K. von Werder ....... 45 A. Stevenaert, A. Beckers,
7. Chemical Structure, Pharmaco- K. Kovacs, E. Bastings,
dynamic Profile and Pharmaco- M. de Longueville, G. Hennen 95
kinetics of SMS 201-995 14. Treatment of Acromegaly with
(Sandostatin®) SMS 201-995 (Sandostatin®):
P. Marbach, H. Andres, M. Azria, Clinical, Biochemical and
W. Bauer, U. Briner, K.-H. Buch- Morphologic Study
heit, W. Doepfner, M. Lemaire, A. L. Barkan, R. V. Lloyd,
T. J. Petcher, J. Pless, J. -C. Reubi 53 W. F. Chandler, M. K. Hatfield,
8. Studies on the Acute and Chronic S. S. Gebarski, R. P. Kelch,
Effects of Sandostatin® in I. Z. Beitins .......... 103
Acromegaly 15. Long-Term Treatment of Acro-
S. W. J. Lamberts .... 61 megaly by Continuous Subcutane-
9. Medical Treatment of Acro- ous Infusion of the Long-Acting
megaly. Dopaminergic Agonists Somatostatin Analog Sando-
and Long-Acting Somatostatin statin® (SMS 201-995, Octreotide)
A. Liuzzi, P. G. Chiodini, J. P. Tauber, Th. Babin,
VI
M. C. R. Ducasse, M. T. Tauber, 22. Successful Treatment of Ophthal
A. G. Harris, F. Bayard . . .. 109 moplegia in Acromegaly with the
16. Sandostatin® (SMS 201-995) Somatostatin Analogue SMS
Treatment of Acromegaly: Acute 201-995 (Sandostatin®)
and Chronic Effects P. A. van Liessum, G. F. F. M.
S. R. George . . . . . . . . .. 113 Pieters, A. R. M. M. Hermus,
17. Long-Term Efficacy of Sando A. G. H. Smals, P. W. C. Kloppen
statin® (SMS 201-995, Octreotide) borg . . . . . . . . . . . . .. 145
in 178 Acromegalic Patients. 23. Sandostatin® (SMS 201-995) in the
Results from the International Treatment of Acromegaly
Multicentre Acromegaly Study M. L. Vance, D. L. Kaiser,
Group M. O. Thorner . . . . . . 149
A. G. Harris, H. Prestele, 24. Somatostatin Octapeptide
K. Herold, V. Boerlin .... 117 (SMS 201-995, Sandostatin®) in
18a. Pulsatile Administration of SMS the Medical Treatment of Acro
201-995 (Sandostatin®) in the megaly
Treatment of Acromegaly J. A. H. Wass, K. Davidson,
H. Imura, Y. Kato, N. Hattori . 127 S. Medbak, G. M. Besser. . 151
18b. Treatment of Acromegaly with 25a. SMS 201-995 (Sandostatin®)
SMS 201-995 (Sandostatin®): Treatment of Therapy-Resistant
A Collaborative Study in Japan Acromegaly
H. Imura, M. Irie ...... 129 J. Schopohl, O. A. Milller,
19. Long-Term Treatment of Resis K. von Werder . : . . . . . .. 153
tant Acromegaly with a Somato 25b. Sandostatin® (SMS 201-995) Can
statin Analog (SMS 201-995, Exert a Direct Analgesic Effect
Sandostatin®) A. Beckers, A. Stevenaert,
I. M. D. Jackson, L. Barnard, E. Bastings, M. de Longueville,
W. Cobb, M. Hein, R. Perez. 133 G. Hennen . . . . . . . . .. 157
20. High-Dose, Long-Term, 25c. Relapsing Acromegaly Resistant
Continuous Subcutaneous Infu to Both Bromocriptine and
sion of SMS 201-995 (Sando Sandostatin®Treatment
statin®) in Acromegaly A. Beckers, A. Stevenaert,
S. Chatterjee, M. C. White, E. Bastings, M. de Longueville,
N. Mrpller, K. Hall, M. J. Dunne, G. Hennen . . . . . . .. . 159
E. R. Baister, P. Kendall-Taylor 137 26. Consensus Discussion and
21. Long-Term Therapy of Acro Conclusions
megalywith SMS 201-995 (Sando J. Ginsburg. . . . . . . . . .. 163
statin®)
D. Killinger, J. Gonzalez. . .. 141
Abbreviations
ACfH adrenocorticotrophic hormone NIDDM non insulin-dependent diabetes
bj.d. bis in die (twice a day) mellitus
Br bromocriptine NMR nuclear magnetic resonance
CSF cerebrospinal fluid NTEL no-toxic-effect level
CSI continuous subcutaneous OD oculus dexter (right eye)
infusion OGTT oral glucose tolerance test
Cf computed tomography OS oculus sinister (left eye)
DA dopamine PET positron emission tomography
FSH follicle stimulating hormone PIIIP procollagen III propeptide
5-FU 5-fluorouracil PRL prolactin
GH growth hormone RER rough endoplasmic reticulum
GHRH growth hormone releasing RIA radioimmunoassay
hormone RRA radioreceptor assay
GnRH gonadotropin releasing hormone Sm-C somatomedin-C
GRF growth hormone releasing factor SMS Sandostatin
HPLC high performance liquid chroma- SRIF, SS somatostatin (somatotropin
tography release inhibiting factor)
IBMX isobutylmethylxanthine t.d.s. ter die sumendum (to be taken
IGFI insulin-like growth factor I three times a day)
IRI immunoreactive insulin TFA total fatty acids
LH luteinizing hormone tj.d. ter in die (three times a day)
LHRH luteinizing hormone releasing TRH thyrotropin releasing hormone
hormone T3RU triiodothyronine resin uptake
MRI magnetic resonance imaging TSH thyroid stimulating hormone
mRNA messenger ribonucleic acid
Authors' Addresses
Baister, Elizabeth, B.Sc., MPS University of Toronto
Clinical Research Associate 200 Elizabeth Street
Medical Department Toronto, Ontario M5G 1C2 (Canada)
Sandoz Pharmaceuticals
98, The Centre Ginsburg, Jean, M.D., D.M., F.R.C.P.
Feltham, Middlesex TW13 4EP The Royal Free Hospital
(Great Britain) London (Great Britain)
Barkan, Ariel, M.D. Harris, Alan G., M.D.
Asst Professor of Internal Medicine Medical Expert
University of Michigan Department of Neuroendocrinology
University Hospital Clinical Research
3920 Taubman Building Sandoz Ltd
Ann Arbor, MI 48109 (USA) Pharma Division
4002 Basle (Switzerland)
Bayard, Francis, M.D.
Professor of Medicine Imura, Hiroo, M.D.
Head, Dept of Endocrinology Professor of Medicine
C.H.U. Rangueil Second Department of Internal Medicine
Universite Paul Sabatier Faculty of Medicine, Kyoto University
Chemin du Vallon Seigoin Kawara-machi, Sakyo-ku
31054 Toulouse Cedex (France) 606 Kyoto (Japan)
Boerlin, Victor, M.D. Jackson, IvorM.D., M.D.
Head, Dept of Neuroendocrinology Professor of Medicine, Physician in Charge
Clinical Research Department of Endocrinology
Sandoz Ltd Brown University, Rhode Island Hospital
Pharma Division 593 Eddy Street
4002 Basle (Switzerland) Providence, Rhode Island 02903 (USA)
Chiodini, Pier Giorgio, M.D. Kendall-Taylor, Pat, M.D., F.R.C.P.
Asst Endocrinologist Professor of Endocrinology
Divisione di Endocrinologia Carati Department of Medicine
Ospedale Niguarda - Cft Granda Royal Victoria Infirmary
Piazza Ospedale Maggiore, 3 Queen Victoria Road
20162 Milan (Italy) NE14LP Newcastle upon Tyne
(Great Britain)
Deidier, Annick, M.D.
Project Leader Killinger, Donald, M.D., M.Sc., Ph.D.,
Clinical Research F.R.C.P. (C)
Laboratoires Sandoz S.ft.f.l. Associate Professor
51 rue Louis Blanc University of Toronto
69006 Lyon (France) Sr Staff Physician and Director
Clinical Investigation Unit
George, Susan R., M.D., Wellesley Hospital
F. R. C. P. (C), F. A. C. P. 160 Wellesley St East
Asst Professor, Attending Staff Physician Toronto, Ontario M4Y 1J3 (Canada)
in Endocrinology
Eaton Wing llN-227
Department of Medicine
Toronto General Hospital
IX
Lamberts, Steven W. J., M.D. Quabbe, Hans-Jiirgen, M.D.
Professor of Internal Medicine Professor of Medicine
Rotterdam, University Hospital, Dijkzigt Medizinische Klinik und Poliklinik
Dr Molewaterplein 40 Universitatsklinikum Steglitz
3015 GD Rotterdam (The Netherlands) der Freien Universitat Berlin
Hindenburgdamm 30
Landolt, Alex M., M.D. 1000 Berlin 45 (West Germany)
Professor of Medicine
Asst Medical Director Sassolas, Genevieve, M.D.
Neurochirurgische Klinik Hopital Neuro-Cardiologique
Universitatsspital Zurich Centre de Medecine Nucleaire
Ramistrasse 100 59 boulevard Pinel
8091 Zurich (Switzerland) 69394 Lyon Cedex 3 (France)
Liuzzi, Antonio, M.D. Stevenaert, Achille, M.D.
Asst Endocrinologist Professor of Neurosurgery
Divisione di Endocrinologia Carati Department of Neurosurgery
Ospedale Niguarda - Ca Granda Hopital de Baviere
Piazza Ospedale Maggiore, 3 Boulevard de la Constitution 66
20162 Milan (Italy) 4020 Liege (Belgium)
de Longueville, Marc, M.D. Thorner, Michael, M.B., F.R.C.P.
Clinical Research Monitor Professor of Medicine
SandozS.A. Head, Division of Endocrinology
Chaussee de Haecht 226 Department of Internal Medicine
1030 Bruxelles (Belgium) University of Virginia, School of Medicine
Box 511
Marbach, Peter, M.D. Charlottesville, Virginia 22908 (USA)
Preclinical Research
Sandoz Ltd Vance, Mary Lou, M.D.
Pharma Division Asst Professor of Medicine
4002 Basle (Switzerland) Department of Internal Medicine
University of Virginia, School of Medicine
0rskov, Hans, M.D. Box 511
Professor of Medicine Charlottesville, Virginia 22908 (USA)
Institute of Experimental Clinical Research
University of Aarhus Wass, John A.H., M.D., F.R.C.P.
Kommunehospitalet Reader in Medicine
8000 Aarhus C (Denmark) and Consultant Physician
Department of Endocrinology
Pieters, Gerlach, M.D. St Bartholomew's Medical School
Radboud Hospital West Smithfield
University of Nijmegen EC 1A 7BE London (Great Britain)
Geertgroteplein 8
Nijmegen (The Netherlands) von Werder, Klaus, M.D.
Professor of Medicine
Pl6ckinger, Ursula, M.D. Asst Medical Director
Medizinische Klinik und Poliklinik Medizinische Klinik Innenstadt
Universitatsklinikum Steglitz der Universitat Munchen
der Freien Universitat Berlin Ziemssenstrasse 1
Hindenburgdamm 30 8000 Munchen 2 (West Germany)
1000 Berlin 45 (West Germany)
Nomenclature
Sandostatin® Octreotide INN (F)
Octreotide INN, BAN Octreotida INN (Span.)
1. Clinical Aspects of Growth Hormone Hypersecretory
States
M. O. Thorner, M. L. Hartman, M. L. Vance
Division of Endocrinology, Department of Intemal Medicine, University of Virginia, School of Medi
cine, Charlottesville, Virginia, USA
Growth hormone (GR) is secreted by the by hypothalamic growth hormone releasing
anterior pituitary and the pattern of secre hormone (GRRH) associated with a reduc
tion in both human and animal species is tion in the tonic secretion of somatostatin
pulsatile [6,19]. Thus, there are episodes of (growth hormone release inhibiting hor
enhanced growth hormone secretion which mone: SS) [18, 22]. Evidence from animal
occur at varying intervals. At present it is studies indicates that pulses of growth hor
not clear whether growth hormone is toni mone secretion require GRRH, since pas
cally secreted between secretory bursts or sive immunization with antibodies to
whether it is only secreted episodically. GRRH abolishes these GR bursts [24]. In
Episodic growth hormone secretion is contrast, basal growth hormone secretion is
thought to be mediated by dual stimulation apparently tonically inhibited by somatosta
tin since passive immunization with an
tibodies to somatostatin leads to an increase
in basal GR secretion [25]. The exact nature
of hypothalamic secretion of somatostatin
and GRRH is speculated to be reciprocal
(Fig. 1) [18,22]. This hypothesis has been
supported by direct sampling of hypo
physeal-portal blood in rats [12].
Growth hormone secretion is also regu
lated by peripheral factors which feed back
at the hypothalamic and pituitary levels.
Somatomedin-C (insulin-like growth factor
I: IGF I) secretion is regulated by growth
hormone when the nutritional state is ade
quate. IGF I feeds back at the pituitary and
the hypothalamic level to inhibit growth
jjJV(}\ hormone secretion. It is also likely that
many other hormonal and metabolic factors
feed back on growth hormone secretion and
this has been extensively reviewed by
Reichlin [13].
i I I I I
Time, h
Growth Hormone Hypersecretory States
Fig. 1. Schematic representation of the postu
Growth hormone secretion is tightly regu
lated rhythmic secretion of SS and GHRH into
lated. The secretion of growth hormone
hypophyseal-portal blood, with the net result on
varies with developmental stage, age,
GH secretion, as observed in plasma. SRIF
somatotropin release inhibiting factor, GRF gonadal function, and sex. At birth growth
growth hormone releasing factor, GH growth hormone secretion is high, declines over the
hormone. (Reproduced by permission from [18]) first few weeks of life, remains low through-