Clinical Applications of Continuous Infusion Chemotherapy and Concomitant Radiation Therapy

240 Pages·1986·13.285 MB·English

by  Branimir Ivan Sikic (auth.), C. Julian Rosenthal M.D., Marvin Rotman M.D. (eds.)

Clinical Applications
of Continuous
INFUSION
CH EMOTH ERAPY
and Concomitant
RADIATION THERAPY
Clinical Applications
of Continuous
INFUSION
CHEMOTHERAPY
and Concomitant
RADIATION TH ERAPY
Edited by
C. Julian Rosenthal, M.D.
Associate Professor of Medicine
Director, Division of Medical Oncology
State University of New York
Health Science Center at Brooklyn
Brooklyn, New York
and
Marvin Rotman, M.D.
Professor and Chairman
Department of Radiation Oncology
State University of New York
Health Science Center of Brooklyn
Brooklyn, New York
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Conference on Continuous Infusion Chemotherapy and its Interactions with Radia
tion in the Treatment of Malignant Tumors (1st: 1985: New York, N.Y.)
Oinical applications of continuous infusion chemotherapy and concomitant radia
tion therapy.
"Proceedings of the First Conference on Continuous Infusion Chemotherapy and its
Interactions with Radiation in the Treatment of Malignant Tumors, held March 22,
1985, in New York, New York"-T.p. verso.
Includes bibliographies and index.
1. Cancer-Adjuvant treatment-Congresses. 2. Antineoplastic agents-Congress
es. 3. Cancer-Radiotherapy - Congresses. 4. Drugs-Administration - Congresses. I.
Rosenthal, C. J. (c. Julian) II. Rotman, Marvin, 1933- . III. Title. IV. Title: Con
tinuous infusion chemotherapy and concomitant radiation therapy. [DNLM: 1. An
tineoplastic Agents-administration & dosage-congresses. 2. Infusions, Parenteral
methods-congresses. 3. Neoplasms-drug therapy-congresses. 4. Neoplasms
radiotherapy-congresses. W3 C572N 1st 1985c / QZ 267 C7472 1985cl
RC271.A35C66 1985 616.99'406 86-4890
ISBN-13: 978-1-4612-9291-3 e-ISBN-13: 978-1-4613-2197-2
001: 10.1007/978-1-4613-2197-28
Proceedings of the First Conference on Continuous Infusion Chemotherapy
and its Interactions with Radiation in the Treatment of Malignant Tumors,
held March 22, 1985, in New York, New York
© 1986 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1986
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
The first conference on concomitant infusion chemotherapy and radia
tion therapy was organized with the intention of bringing together some
of the investigators who have tested, during the last few years, the hypo
thesis that continuous infusion chemotherapy could modulate the cytotoxic
effect of radiation therapy to the point of having a strongly additive,
if not synergistic activity on certain malignant tumors.
This volume represents the detailed proceedings of this conference
presented in a way that offers the reader a review of the on-going re
search in the field. We have stressed a number of subjects from basic
biologic research and influence of cell kinetics to the practical methods
of drug delivery systems and early clinical experiences.
The rationale for this new type of combined modality therapy has been
presented by some of its pioneers. Early clinical investigations as well
as the preliminary data of many that have not yet completely matured have
also been included. The reader should look at these data with some reser
vations. Ultimately, these results must be confirmed by larger prospective
randomized studies with proper controls before becoming accepted as the
treatment of choice in locally advanced tumors.
It is our hope that this volume will succeed in bringing to the inter
ested medical community a new approach in clinical medicine which, in
paraphrasing Konrad Lorenz can be considered as "the working hypothesis
best suited to open the way to the next better one", aiming ultimately at
the ablation of localized malignant tumors with a minimum of morbidity.
C. Julian Rosenthal
}~rvin Rotman
v
CONTENTS
SECTION I
PROTRACTED DELIVERY OF ANTINEOPLASTIC CHEMOTHERAPY AGENTS
A. Principles and Therapeutic Applications
Theoretical, Clinical and Pharmacokinetic Aspects
of Cancer Chemotherapy Administered by
Continuous Infusion • • • • • • • • • • • • 3
B.1. Sikic
Pharmacology and Therapeutic Efficacy of Bleomycin
Administered by Continuous Infusion •• • • • 13
1.H. Krakoff
Continuous-Infusion Adriamycin • • • • • • • • • • • • • • 19
R.S. Benjamin, S.P. Chowla, G.N. Hortobagyi, M.S. Ewer,
B. Mackay, S,S. Legha, H. Carrasco, and S. Wallace
5-Fluorouracil Plus Thymidine or Leucovorin by
Continuous i.v. Infusion in the Treatment of
Advanced Colorectal Carcinoma •• • • • • • 27
F. Trave and Y.M. Rustum
Epipodophyllotoxin and Cisplatin on Continuous
Infusion Schedules • • • • • • • • • • 43
J.J. Lokich
Biodegradable Starch Microspheres (SPHEREX): A Clinical
Useful Medical Device for Combined Intra-arterial
Chemotherapeutic Treatment of Primary and
Metastatic Cancers of the Liver • • • • • • • • • 51
G. Parker and W. Regelson
Selective Therapy of Hepatic Cancers Using Microspheres • • • • • 67
J.W. Gyves
B. Clinical Studies
Preliminary Results of a Randomized Study of Intrahepatic
Infusion Versus Systemic Infusion of FUDR
for Metastatic Colorectal Carcinoma 73
N. Kemeny and J. Daly
vii
COPBLAM: Infusion Chemotherapy for Large Cell Lymphoma 79
M. Coleman, B. Boyd, B. Bernhardt, G. Gerstein,
and S. Kopel
Adriamycin Continuous i.v. Infusion for the Treatment
of Childhood Hepatic Halignancies, Toxicity and
Efficacy: A Pilot Study Childrens Cancer Study Group 87
J.A. Ortega, W. Woods, J. Feusner, G. Reaman,
B. Lange, and G.D. Hammond
An Uncontrolled Phase II Study of Constant Infusion
Vincrist ine-Adriamycin • • • • • • • • • • • • 91
L. Helson, M.A. Costello, E. Arenson,
L. Steinherz, and S. Groshen
Low Dose Ara-C by Continuous Infusion in the Treatment
of Acute Non-Lymphocytic Leukemia (ANLL) and
Hyelodysplastic Syndrome (HDS) .•••••• 95
F. Chaudri, S.L. Allen, P. Schulman, W. Kreis,
D.R. Budman, L. Weiselberg, and V. Vinceguerra
The 5-Day Continuous Infusion of Cis-platinum: An
Update on Toxicity Pattern 101
P. Salem, M. Khalyl, K. Jabboury, and L. Hashimi
Long Term Appraisal of the Lemon-Foley Hethod of Chemotherapy
of Solid Tumors of the Gastrointestinal Tract ••••• 107
D. Steinberg
SECTION II
ANTINEOPLASTIC EFFECTS OF RADIATION THERAPY AND CONCOMITANT
CHEHOTHERAPY BY CONTINUOUS INFUSION
A. Principles and Therapeutic Applications
Theoretical Basis and Clinical Applications of
5-Fluorouracil as a Radiosensitizer 113
J.E. Byfield
Treatment of Hepatic Hetastases from Gastro Intestinal
Primaries with Split Course Radiation Therapy
and Concomitant Infusion 5-Flourouracil 127
M. Rotman, I. Bhutiani, A. Kuruvilla, K. Choi,
C.J. Rosenthal, A. Braverman and J. Marti
Combined Modality Therapy with 5-Fluorouracil, Mitomycin-C
and Radiation Therapy for Squamous Cell Cancers 133
B.J. Cummings, T.J. Keane, A.R. Harwood, and G.M. Thomas
Treatment of Bladder Carcinoma with Concomitant Infusion
Chemotherapy and Irradiation • • • • • • • • 149
M. Rotman, R. Macchia, M. Silverstein, K. Choi,
C.J. Rosenthal, A. Braverman and M. Aziz
A Urologist's Viewpoint: Treatment of Invasive Bladder
Cancer by the XRT/5FU Protocol •••••••••• 155
R.J. Macchia and G. Langauni
viii
Concomitant Radiation Therapy and Doxorubicin by
Continuous Infusion in Advanced Malignancies - A
Phase I-II Study - Evidence of Synergistic Effect
in Soft Tissue Sarcomas and Hepatomas • • • • • • 159
C.J. Rosenthal, M. Rotman, and I. Bhutiani
Cis Platin by Continuous Infusion with Concurrent
Radiation Therapy in Malignant Tumors (A Phase I-II
Study) . . • . . • . • • • • • • • • • • ••. 177
C.J. Rosenthal, M. Rotman, K. Choi and J. Sand
B. Clinical Studies
Combination of Radiation with Concomitant Continuous
Adriamycin Infusion in a Patient with Partially Excised
Pleomorphic Soft Tissue Sarcoma of the Lower Extremity • 183
S. Turner, R. Shetty, H. Gandhi, A. Latyshevsky,
J. Korzis and R. Yaes
Treatment of Recurrent Carcinoma of the Parana sal Sinuses
Using Concomitant Infusion Cis-platinum And Radiation
Therapy • • . • • . • . • • • • . . • . • • • • . • . • . ~. 189
M. Rotman, K. Choi, S. Isaacson, C.J. Rosenthal,
A. Braverman, and J. Harti
Hepatic Artery Infusion (HAl) for Hepatic Metastases in
Combination with Hepatic Resection and Hepatic Radiation 195
R.W. Merrick, R.R. Dobelbower, Jr., J.F. Ringleiut,
and R.T. Skeel
Phase II Study of Simultaneous Radiation Therapy, Continuous
Infusion, 5-FU and Bolus Mitomycin-C ••••••••• 201
O.A. Mendiondo, L.C. Maguire, W.D. Medina, and J.D. Cronin
Cancer of the Esophagus - Medical University of
South Carolina Pilot Study • • • • • • • • • • • • 207
J.M. Jenrette, III, R.D. Marks Jr., E.F. Parker, and
R.H. Fitzgerald Jr.
Continuous Infusion VP-16, Bolus Cis-Platinum and
Simultaneous Radiation Therapy as Salvage Therapy
in Small Cell Bronchogenic Carcinoma • • • • • 211
K. Rowland Jr., P. Bonomi, S. Taylor, S. Maffey,
S. Reddy, and M.S. Lee
Concomitant Radiation, Mitomycin-C and 5-Fluorouracil
Infusion in Gastro Intestinal Cancer - A
Preliminary Report • • • • • 217
A. Chan, A. Wong and K. Arthur
SECTION III
TECHNIQUES FOR THE ADMINISTRATION OF CHEMOTHERAPY AGENTS
BY CONTINUOUS INFUSION
Procedures for the Use of Implantable and External Pumps
for Continuous Infusion Chemotherapy • • • • • • • • 223
B.B. Willis
ix
Central Line Catheter Care: The Nurses' and Patients
Perspective 229
M.J. Tunny
Potential Complications of Right Atrial Catheterization • • • • 233
R.M. Stillman
Long Term Complications of the Indwelling Central
Line Catheters •••••••••••• • 239
J. Marti
INDEX 243
x
INTRODUCTION
The history of cancer therapy has known, from its earliest descrip
tions in ancient Egyptian papyruses (Petrie, Smith, Ebbers) (1), centur
ies of frustration. It was not until the technical revolution of the late
nineteenth century which led to the introduction of radiation therapy in
the treatment of cancer was there a major therapeutic potential for er
radication of malignant diseases. However, the massive single exposures
of radiation and their accompanying high morbidity and local failure rate
plunged this new medical discipline into a period of disillusionment and
frustration. Only after Claude Regaud, in 1919, found that fractionated
radiation directed to the testicle was capable of eliminating spermata
genesis without affecting the surrounding tissues was the treatment of
cancer with radiation revived (2). This technique applied to the therapy
of malignant tumors of the head and neck and cervix and improved disease
control without the then high anticipated complication rate (3). The
later technologic advances of kilovoltage and megavoltage succeeded to
improve on the early results. Nevertheless, the incidence of local and
regional disease failure remained high while other tumors such as the
soft tissue sarcomas were seemingly unresponsive to radiation.
It has been close to half a century since initial radiobiological ex
periments pointed out the radiosensitizing effects of oxygen and the radio
resistance afforded by hypoxia. Since that time, efforts to overcome
radio-resistance have been directed towards refining the treatment tech
niques, using the sophisticated plans of high energy machines. It is
primarily with the improved understanding of tumor biology in the last
two decades that attempts to overcome this hypoxic fraction of tumor cells
had led to the use of heavy particle irradiation, hyperthermia, hyperfrac
tionation and, in particular, to the investigation of radiosensitizers.
It had been hoped that electron-affinic compounds would selectively radio
sensitize the resistant poorly oxygenated tissues to the usual dose of
radiation. The nitromidazol compounds and their analysis have as yet not
shown the ability to radiosensitize tumor cells; innate toxicities have
prevented their use in concentrations required for tumor response. The
failure thus far of the electron-affinic compounds lead investigators to
l09k at the concomitant use of radiation therapy and chemotherapy.
The evolution of chemotherapy contains events similar to those found
in the history of radiation therapy. Initially, in the 1940's alkylating
agents showed promise of disease erradication. The morbidity and lack of
tumor sterilization prompted the continued production of new drugs for
the much sought after cancer "cure". Soon methotrexate followed by cor
ticosteroids and certain antibiotics (4) were found capable of inducing
partial tumor response. When used in combination, these drugs produced
prolonged complete remissions equivalent to cures, in some cases, of acute
lymphocytic leukemias, advanced lymphomas and choriocarcinomas in females.
xi
The discovery of new drugs over the next few decades (Bleomycin, Cis
platin, Etoposide) enlarged the percentages of response rates but did not
significantly reduce recurr~nce rates.
Attempts to increase antineoplastic activity by concentrating the
drugs to the tumor site have included their intracavitary or intra-arter
ial administration. In the past decade administration by continuous
intravenous infusion was encouraged by experimental in-vitro data (5)
which showed that the cytocidal effect of various antineoplastic chemo
therapy agents related not only to concentration of drugs but to their
duration of contact with the malignant cells.
This belief was reinforced by the clinical observations of Nigro (6),
Byfield (7), Sischy (8), Cummings (9) and Rotman indicating that squamous
cell carcinoma 'of the anus and esophagus, adenocarcinoma of the rectum
and transitional cell carcinoma to the bladder would regress when exposed
to infusion 5FU and radiotherapy. In addition, early phase II studies
conducted by Rosenthal, Rotman, et. al. (10,11) suggested a synergistic
antineoplastic effect of radiation therapy and continuous infusion adria
mycin for selective soft tissue sarcomas and hepatomas as well as of in
fusion cisplatin and radiation therapy for some advanced squamous cell
carcinomas (12). There are not, as yet, controlled prospective random
ized studies to demonstrate the clinical benefits of the combined concom
itant modalities versus radiation therapy alone. Despite this, the edi
tors of this volume thought that there was enough merit in the pilot work
on continuous infusion chemotherapy and irradiation to'lead to the organ
ization of the first conference on continuous infusion chemotherapy and
concomitant radiation therapy.
The intention of the editors of this volume was not to exhaustively
review all the pioneering clinical and basic scientific work which led to
the current status of the concomitant use of radiation and infusion chemo
therapy nor to include results of all the past or ongoing clinical trials
in this field. Rather, this volume intends to bring to the attention of
clinicians and clinical investigators, the most promising data of a new
therapeutic approach in which we think significant progress in the therapy
of malignant tumors will be registered and, hopefully, to raise the inter
est of many clinicians to this area of fruitful clinical research. In
this respect, we would like to caution the readers against the casual ap
plication of the methods described in the various chapters. They should
be applied only in centers Hhere rigorous control of the techniques and
appropriate supportive therapy are available and always within the frame
work of Internal Research Board approved investigative protocols. The
editors and the publisher cannot guarantee the accuracy of the drug dos
age listed in various papers. No regimen listed in the various articles
of this book should be administered without prior consultation with the
author(s) of the article describing it.
We would also like to acknowledge the invaluable secretarial help of
Ms. Amrani and Ms. Dutka, the expert editorial help of Ms. Raynor-Enco
and the support received from the American Cancer Society (grant #2484),
National Cancer Institute (grant #2R25CA1798206) and the Bristol Company
without which the conference and this volume on concomitant continuous
infusion chemotherapy and radiation therapy would have not been possible.
September 18, 1985 C. Julian Rosenthal
Marvin Rotman
xii