Photodynamic Therapy-Basic Principles and Clinical Applications

480 Pages·1992·34.248 MB·\480

by  Barbara W. Henderson (Author)

PHOTODYNAMIC
THERAPY

PHOTODYNAMIC
THERAPY
BASIC PRINCIPLES AND
CLINICAL APPLICATIONS
EDITED BY
BARBARA W. HENDERSON
THOMAS J. DOUGHERTY
Roswell Park Cancer Institute
Buffalo, New York
Marcel Dekker, Inc. New York • Basel • Hong Kong
Library of Congress Cataloging-in-Publication Data
Photodynamic therapy : basic principles and clinical applications /
edited by Barbara W. Henderson, Thomas J. Dougherty.
p. cm.
Includes bibliographical references and index.
ISBN: 978-0-8247-8680-9
1. Cancer—Photochemotherapy. I. Henderson, Barbara W.
II. Dougherty, Thomas J. (Thomas John).
[DNLM: 1. Neoplasms-therapy. 2. Photochemotherapy. WB 480
P575433]
RC271.P43P45 1992
616.99'40631--dc20
DNLM/DLC
for Library of Congress 92-14636
CIP
This book is printed on acid-free paper.
Copyright © 1992 by MARCEL DEKKER, INC. AH Rights Reserved
Neither this book nor any part may be reproduced or transmitted in any form
or by any means, electronic or mechanical, including photocopying, micro-
filming, and recording, or by any information storage and retrieval system,
without permission in writing from the publisher.
MARCEL DEKKER, INC.
270 Madison Avenue, New York, New York 10016
Current printing (last digit):
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PRINTED IN THE UNITED STATES OF AMERICA
Preface
In this volume, the molecular and cellular mechanisms of PDT that are at the
root of all PDT tissue effects are broadly covered, illustrating the wide range of
possible target sites within the cell. The complex interplay of events leading to
acute and delayed tissue effects by PDT as well as the subsequent healing pro-
cesses are described. Here, particular emphasis has been placed on photosensi-
tizer structure/activity relationships since it is our belief that ultimately the
understanding of PDT mechanisms and improvements of the clinical modality
will depend on our understanding of these relationships. Also discussed are new
approaches to photosensitizer delivery that may improve treatment selectivity.
Outstanding contributions deal with advances in light delivery and dosimetry,
as well as the implications of sensitizer photobleaching and the application of
PDT technology to the detection of malignancies.
A comprehensive summary of all clinical studies has been provided, high-
lighted by results from the first Phase HI clinical trial, on the use of PDT for
prophylaxis of recurrence of bladder cancer after tumor removal. The interna-
tional acceptance of PDT as a promising clinical modality is evident in the con-
tributions that outline the Japanese and German collaborative studies. The
innovative clinical approaches to intraperitoneal and intrapleural PDT that are
being developed at the National Cancer Institute in the United States are de-
scribed, and discussions of the value of PDT for the treatment of early cancer
and for palliation have been included.
ill
iv Preface
While the accumulation of clinical data from controlled, randomized trials is
proceeding toward the goal of regulatory approval, and all facets of the com-
mercialization of this modality—development of new drugs and technology,
manufacture, and marketing—are moving forward, turning our attention to the
future, we also wished to cast a glance back to the earliest beginnings of the field
of PDT. We have therefore asked Drs. Schwartz, Lipson, and Winkelman for
their personal accounts of their pioneering experiences with PDT and gratefully
acknowledge their contributions to PDT and to this book.
We wish to express to the contributors our great appreciation of their efforts.
And, finally, special thanks are due to Judy Felski, whose help in the editing
process was invaluable.
Barbara W. Henderson
Introduction
Looking at the number of excellent presentations and the number of attendees at
the Third Meeting of the International Photodynamic Association in 1990 in
Buffalo, New York, and remembering the very first such meeting in Buffalo in
1979,1 am reminded of one of the more notorious advertisements of recent years
for a product that shall go unnamed: "You've come a long way, Baby!" How-
ever, I must confess to having felt this way before, especially in 1985 when a
large pharmaceutical company that shall also go unnamed took up Photody-
namic Therapy for health agency approvals and commercialization. I am hopeful
that this time it will be different. In 1985 I was naive about drug approval pro-
cesses, especially in the United States. In spite of the fact that Roswell Park
Cancer Institute had the first IND for therapeutic use of a photosensitizer (Hpd)
and that we have treated nearly 1000 patients by PDT here since 1976 and as-
sisted other centers in treating many thousands more, I was unaware of the
proper way to design and carry out a clinical trial for FDA approval. I learned
a little when I interacted periodically with the FDA and assisted in the setting up
of Phase III trials for lung and bladder cancer in 1985-1986.
Having now had the experience of working with the Lederle team, I can
assure you it is a totally different ballgame. Not that there are no skeptics within
that organization. There are. However, they appear willing to be convinced by
results. At Lederle, all aspects of drug approval have been involved from
the beginning, besides the clinical project and all the experienced medical
research associates, these include analytical, drug manufacture, development,
vi Introduction
marketing, and international distribution. This is a coordinated team under a
very capable manager. Lederle/QLT are sponsoring Phase III trials in the United
States and Europe (bladder, esophagus, lung) and Lederle Japan is carrying out
clinical trials of PDT for several indications of early stage cancers (lung, esoph-
agus, gastric, bladder, cervical). In addition, since Lederle/QLT took over, over
250 patients have been treated by "compassionate" PDT, meaning that PDT is
essentially the only reasonable alternative for those particular patients. Both
Lederle and the FDA have been very open to such treatments. Also, Lederle and
QLT have allowed some 25-30 centers to obtain a cross-filing to the QLT IND
for those institutions to obtain their own INDs for a wide variety of other PDT
Phase I/II trials (e.g., breast mets, intraoperative PDT, gyn, basal cell, Kaposi's
sarcoma, papillomatosis, psoriasis, and many others). On a positive note, the
National Cancer Institute has actively developed several innovative clinical trials
for intraperitoneal and intrapleural PDT, and Southwestern Oncology Group
(SWOG) is developing a PDT protocol for bladder cancer, so at least in this
regard, PDT has become a part of the "cancer establishment." (Is that good
or bad?)
Since this meeting Lederle has released the results of one of their Phase III
trials in bladder cancer; that is, PDT for prophylaxis of papillary bladder cancer
following tumor removal (TUR) vs observation following TUR (current prac-
tice). Using percent and time to recurrence as end points, the differences in the
two arms were large enough that this particular study was terminated with only
39 total patients. The current recurrence rate is 39% versus 81% (PDT versus
observation) and, more significantly, the median time to recurrence is 394 ver-
sus 91 days for PDT versus observation, respectively (in fact, the mean time to
recurrence for the PDT arm has not yet been reached). This study, if confirmed
(a second similar study is now underway), indicates a unique role for PDT in
bladder cancer (preliminary data on PDT for carcinoma-in-situ in the bladder are
also promising). In my opinion, this "uniqueness" (i.e., ability to treat other-
wise untreatable disease) is going to be essential for the acceptance of PDT by
the practicing clinicians since it is not a particularly easy technique to master.
Finally, while tricky to predict, the odds are that by the time this volume is
published, the first approval of PDT by a health agency will have occurred, with
many others to follow over the next 1-3 years. There are many scientific and
clinical investigators, many represented in this meeting, who have played im-
portant roles over the past decade(s) and who will be responsible for the ultimate
success of PDT. It was particularly gratifying to be able to honor the very ear-
liest—Drs. Schwartz, Lipson and Winkelman, at this meeting.
Thomas J. Dougherty
Contents
Preface Hi
Introduction v
1. Historical Perspective 1
Thomas J. Dougherty, Barbara W. Henderson, Samuel Schwartz,
James W. Winkelman, Richard L. Lipson
1. MOLECULAR AND CELLULAR EFFECTS OF
PHOTODYNAMIC THERAPY
2. Fluorescence and Photodynamic Effects of Phthalocyanines
and Porphyrins in Cells 19
Johan Moan, Kristian Berg, Harold B. Steen, Trond Warloe,
and Karl Madslien
3. Photodynamic Therapy: Membrane and Enzyme Photobiology 37
Tom M. A. R. Dubbelman, Carla Prinsze, Louis C. Penning, and
J. van Steveninck
vii