The Role of Pharmacology in Pediatric Oncology

307 Pages·1986·14.224 MB·English

by  Jerry M. Collins (auth.), D. G. Poplack, L. Massimo, P. Cornaglia-Ferraris (eds.)

THE ROLE OF PHARMACOLOGY IN PEDIATRIC ONCOLOGY
DEVELOPMENTS IN ONCOLOGY
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THE ROLE OF
PHARMACOLOGY IN
PEDIATRIC ONCOLOGY
edited by
D.G. POPLACK
Leukemia Biology Section, Pediatric Branch
National Institutes oj Health, Bethesda, Maryland, U.S.A.
L. MASSIMO and P. CORNAGLIA-FERRARIS
Istituto Giannina Gaslini
Genova, Italy
ia.
1987 MARTINUS NIJHOFF PUBLISHERS
a member of the KLUWER ACADEMIC PUBLISHERS GROUP •
DORDRECHT / BOSTON / LANCASTER
Distributors
for the United States and Canada: Kluwer Academic Publishers, P.O. Box 358,
Accord Station, Hingham, MA 02018-0358, USA
for the UK and Ireland: Kluwer Academic Publishers, MTP Press Limited, Falcon
House, Queen Square, Lancaster LA1 1RN, UK
for all other countries: Kluwer Academic Publishers Group, Distribution Center,
P.O. Box 322, 3300 AH Dordrecht, The Netherlands
Library of Congress Cataloging in Publication Data
The Role of pharmacology in pediatric oncology.
(Developments in oncology)
Includes bibliographies and index.
I. Tumors in children--Chemotherapy. 2. Pediatric
pharmacology. I. Poplack, David G. II_ Massimo,
Luisa. III. Cornaglia Ferraris, Paolo. IV. Series.
[DNLM: 1. Neoplasms--drug therapy. 2. Neoplasms--
in infancy & childhood. WI DE998N I QZ 267 R745]
RC281.C4R65 1986 618.92'99'2061 86-687
ISBN-13:978-94-010-8395-9 e-ISBN-13:978-94-009-4267-7
DOl: 10.1007/978-94-009-4267-7
ISB~-13:978-94-010-8395-9
Copyright
© 1987 by Martinus Nijhoff Publishers, Dordrecht.
Softcover reprint of the hardcover 1st edition 1987
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,
photocopying, recording, or otherwise, without the prior written permission of
the publishers,
Martinus Nijhoff Publishers, P.O. Box 163, 3300 AD Dordrecht,
The Netherlands.
v
Preface
The dramatic improvement made in recent years in the treatment of child
hood malignancies has been in large part the result of advances in the field
of pharmacology. Chemotherapy is the major therapeutic modality used to
treat childhood cancer. Rational administration of antineoplastic chemo
therapy to the child with cancer requires the pediatric oncologist to have a
thorough understanding of the fundamental principles of clinical pharmaco
logy, an intimate knowledge of the specific agents being used, and an aware
ness of the unique biologic and physiologic features of children.
In mid 1985, a distinguished group of pediatric oncologists and clinical
pharmacologists convened in a unique workshop to review the subject of
pharmacology in pediatric oncology. A goal of this workshop was to pro
duce a book which would review this topic and present it in a format useful
for the clinician.
In this book basic principles of pharmacology, mechanisms of drug resis
tance, new methods of drug delivery, guidelines for studying new agents in
children, new biological response modifiers and the pharmacology of the
most commonly used chemotherapeutic agents in children are reviewed in
depth. Particular emphasis is given to discussing those topics which unique
ly apply to the use of antineoplastic agents in children with cancer.
The Editors
VII
Contents
Preface . v
Contents
Vll
List of Major Contributors
Xl
Principles of Antineoplastic Therapy in Children
1. Clinical pharmacokinetics for the pediatric oncologist
J.M. Collins ................ . 3
2. The pharmacology of antine'Oplastic agents in children
F.M. Balis .................. . 15
3. Clinical pharmacology of anticancer drugs in children: differences
and similarities between children and adults
W.E. Evans, c.F. Stewart, M.L. Christensen and W.R. Crom 29
Pharmacologic reasons for treatment failure
4. Drug resistance in medical and pediatric oncology
K.H. Cowan ............... . 75
5. Genetic reasons for pharmacologic treatment failure: gene amplif
ication
G. Torelli 89
6. New approaches to overcome drug resistance
v. Avramis, R. Biener and J. Holcenberg .. 97
VIII
Methods of drug delivery
7. New methods of administering old drugs: iv infusion of mercap
topurine
S. Zimm and D.G. Poplack .. 115
8. Regional therapy: an overview
J.M. Collins ....... . 125
9. Pharmacologic approaches to the treatment of central nervous sys
tem malignancy
D.G. Poplack and R. Riccardi .............. 137
Use of new agents in children
10. Phase I and II trials in pediatric cancer patients: a rationale
R.S. Ungerleider and S. Marsoni . . . . . . . . . 159
11. Guidelines for conduct of Phase I studies in children
J. Holcenberg ................ . 171
Pharmacology of antileukemic agents
12. Factors affecting the clinical pharmacology of antileukemic
drugs
R. Riccardi, A. Lasorella and R. Mastrangelo 179
13. Potentiation of 6-mercaptopurine after time and dose-dependent
pretreatment with methotrexate in malignant human T- and B
lymphob1asts.
J.P.M. Bokkerink, R.A. De Abreu, M.A.H. Bakker and T.W.
Hulscher ...................... . 185
14. The effect of methotrexate on purine and pyrimidine deoxyribo
nucleoside triphosphate pools and on cell viability and cell-phase
distribution in malignant human T - and B-Iymphoblasts
R.A. De Abreu, J.P.M. Bokkerink, M.A.H. Bakker, T.W. Hulsch
er and J.M. van Baal . . . . . . . . . . . . . . . . . . 193
15. 7-Hydroxy-methotrexate production after methotrexate therapy
R. Erttmann . . . . . . . . . . . . . . . . . . . . . . 201
Late effects of chemotherapy
16. An overview of adverse late effects of cancer chemotherapy in
children
W.A. BIeyer . . . . . . . . . . . . . . . . . . . . .. 207
IX
17. Focusing on late effects in long-term survivors of childhood leu
kemia and lymphomas
L. Massimo, M.L. Garre, S. Gandus, B. Cesana, R. Haupt, B. De
Bernardi, A. Comelli, E. Casari, C. Querci, M. Cotellessa, P. Cor
naglia, A. Ferrando, G.F. Gargani, G. Stella, M.L. Vitali and A.
Pelizza ........................ 21 7
High dose chemotherapy
18. Purging procedures: a critical step in autologous bone marrow
transplantation
T. Philip, M. Favrot, I. Philip, P. Biron and R. Pinkerton 237
19. 'High dose' cisplatinum: a phase II study
G. Dini, D. Rogers, A. Garaventa, E. Lanino, G.P. Perin, M.
Stura, S. Dallorso, G. Squazzini and B. De Bernardi .... 255
Biological response modifiers
20. Induction of differentiation: a possible therapeutic approach to
the treatment of hematologic malignancy
F. Gavosto, W. Piacibello and M. Aglietta . . . . . . . .. 265
21. The development of 9-substituted purines as immunomodula
tors
A. Giner-Sorolla and J.W. Hadden 275
22. Immunopharmacologic profile of an L-Arginine hypoxanthine
dervative: PCF/OI
P. Cornaglia-Ferraris 285
23. Antineoplastic drugs modulating c-myc expression in K562, in
duce erythroid differentiation and modify, with IFN, susceptibil
ity to NK cell mediated lysis
G.P. Tonini . . . . . . . . . . . . . . . . . . . . .. 294
24. In vivo treatment with recombinant interleukin-2 (IL-2) stimu
lates the differentiation of natural killer (NK) precursor cells
C. Riccardi, G. Migliorati, A. Giampietri, L. Cannarile, E. Ayrol-
di and L. Frati . . . . . . . . . . . . . . . . . . . .. 303
25. Immunopharmacology studies related to in vitro infection with
HTLV-I
C. Grandori, G. Graziani, c.F. Perno, C. D'Onofrio and E. Bon-
massar 309
Index 321
XI
List of major contributors
Vassilios AVRAMIS, Department of Pediatrics, Children's Hospital at Los
Angeles, P.O. Box 54700, Los Angeles, CA 90054-0700, U.S.A.
Frank BALIS, Pediatric Branch, National Cancer Institute, NIH, Building 10,
Room 13N240, Bethesda, MD 20205, U.S.A.
W.A. BLEYER, Children's Orthopedic Hospital, P.O. Box C5371, 4800 Sand
Point Way, N.E., Seattle, WA 98105, U.S.A.
Jos P.M. BOKKERINK, Center for Pediatric Oncology S.E. Netherlands,
Department of Pediatrics, Catholic University of Nijmegen, P.O. Box
9101, 6500 HB Nijmegen, The Netherlands.
Jerry COLLINS, Clinical Pharmacology Branch, National Cancer Institute,
NIH, Building 10, Room 6Nl19, Bethesda, MD 20205, U.S.A.
P. CORNAGLIA-FERRARIS, Department of Pediatric Oncology, G. Gaslini
Institute for Children, 1-16148 Genova, Italy.
Kenneth COWAN, Clinical Pharmacology Branch, National Cancer Institute,
NIH, Building 10, Room 6N116, Bethesda, MD 20205, U.S.A.
Ronney A. DE ABREU, Center for Pediatric Oncology S.E. Netherlands,
Department of Pediatrics, Catholic University of Nijmegen, P.O. Box
9101, 6500 HB Nijmegen, The Netherlands.
G. DINI, Division of Hematology and Oncology, G. Gaslini Institute for
Children, 1-16148 Genova, Italy.
R. ERTTMANN, Department of Hematology and Oncology, Children's Hos
pital, University of Hamburg, Martinistrasse 52, D-2000 Hamburg 20,
F.R.G.
Williams EVANS, Clinical Pharmacokinetics Laboratory, St. Jude Children's
Research Hospital, 332 N. Lauderdale, Memphis, TE 38105, U.S.A.
Felice GAVESTO, Medical Clinic I, Via Genova 3, 1-10126, Torino, Italy.
A. GINER-SOROLLA, Program of Immunopharmacology, College of Medi
cine, University of South Florida, Tampa, FL 33612, U.S.A.
XII
C. GRANDORI, Department of Experimental Medicine and Biochemical
Science, Second University of Rome, Via Orazio Raimondo, 1-00173
Roma, Italy.
John HOLCENBERG, Division of Hematology and Oncology, Children's Hos
pital at Los Angeles, P.O. Box 54700, Los Angeles, CA 90054-0700,
U.S.A.
L. MASSIMO, Department of Pediatric Hematology and Oncology, G. Gas
lini Institute for Children, 1-16148 Genova, Italy.
Thierry PHILIP, Centre Uon Berard, 28 Rue Laennec, F-69008 Lyon Cedex
02, France.
David G. POPLACK, Leukemia Biology Section, Pediatric Branch, National
Cancer Institute, NIH, Building 10, Room 13N240, Bethesda,
MD 20205, U.S.A.
Carlo RICCARDI, Institute of Pharmacology, University of Perugia, Via del
Giochetto, 1-06100 Perugia, Italy.
Riccardo RICCARDI, Institute of Clinical Pediatrics, Catholic University of
Roma, Largo A. Gemelli 8, 1-00168 Roma, Italy.
Gian Paolo TONINI, Pediatric Oncology Research Laboratory, Department
of Pediatric and Oncology, G. Gaslini Institute for Children, 1-16148
Genova, Italy.
Guiseppe TORELLI, Medical Clinic II - Policlinic, Via del Pozzo 71, 1-
41100 Modena, Italy.
Richard UNGERLEIDER, Cancer Treatment Evaluation Program, National
Cancer Institute, NIH, Landow Building, Room 4A-12, Bethesda,
MD 20205, U.S.A.
Solomon ZIMM, Pediatric Branch, National Cancer Institute, NIH, Building
10, Room 13N240, Bethesda, MD 20205, U.S.A.