Biology and Management of Lung Cancer

Transcription

1 Biology and Management of Lung Cancer

2 Cancer Treatment and Research WILLIAM L. MCGUIRE, series editor 1. R. B. Livingston, ed., Lung Cancer ISBN G. B. Humphrey, L. P. Dehner, G. B. Grindey and R. T. Acton, eds., Pediatric Oncology ISBN J.J. DeCosse and P. Sherlock, eds., Gastrointestinal Cancer ISBN J.M. Bennett, ed., Lymphomas ISBN C.D. Bloomfield, ed., Adult Leukemias ISBN D. F. Paulson, Genitourinary Cancer ISBN F.M. Muggia, ed., Cancer Chemotherapy ISBN G. B. Humphrey and G. B. Grindley, Pediatric Oncology ISBN John J. Costanzi, ed., Malignant Melanoma ISBN C. T. Griffiths, A. F. Fuller, ed., Gynecologic Oncology ISBN

3 Biology and Management of Lung Cancer edited by F. ANTHONY GRECO Department of Medicine, Vanderbilt University Medical Center,Nashville, Tennessee, USA 1983 MARTINUS NIJHOFF PUBLISHERS a member of the KLUWER ACADEMIC PUBLISHERS GROUP BOSTON / THE HAGUE / DORDRECHT / LANCASTER... "

4 IV Distributors for the United States and Canada: Kluwer Boston, Inc., 190 Old Derby Street, Hingham, MA 02043, USA 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 Main entry under title: Biology and management of lung cancer. (Cancer treatment and research; v. 11) 1. Lungs--Cancer. I. Greco, F. Anthony (Frank Anthony), II. Series. [ DNLM: 1. Lung neoplasms. WI CA693 v.1l I WF 658 B6l5J RG2.80.L.8B ' ISBN-13: e-isbn-13: : / Copyright 1983 by Martinus Nijhoff Publishers, Boston. Softcover reprint of the hardcover 1 st edition 1983 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, 190 Old Derby Street, Hingham, MA 02043, USA.

5 Contents Foreword Preface List of Contributors VII IX xiii 1. The In Vitro Growth and Characterization of Small Cell Lung Cancer.... DESMOND N. CARNEY, ADI F. GAZDAR, HERBERT K. OlE, FRANK CUTTITTA and JOHN D. MINNA 2. Monoclonal Antibodies Against Human Lung Cancer: Potential Diagnostic and Therapeutic Use FRANK CUTTITTA, STEVEN ROSEN, DESMOND N. CARNEY, ADI F. GAZDAR and JOHN D. MINNA 3. Transforming Growth Factors (TGFs) and Human Lung Cancer Cells STEPHEN A. SHERWIN and GEORGE J. TODARO 4. Tumor Cloning Assay: Application and Potential Usefulness in Lung Cancer Management S. KENT CALLAHAN, CHARLES A. COLTMAN Jr., CLIFF KITTEN and DANIEL D. VON HOFF 5. Autologous Bone Marrow Transplantation - Potential Usefulness in Lung Cancer Management STEVEN N. WOLFF 6. Diagnosis of Poorly Differentiated Carcinomas of the Lung 87 JOHN M. LUKEMAN and BRUCE MACKAY 7. Morphologic Changes in Small Cell Lung Cancer 109 MEHMET F. FER, WILLIAM W. GROSH and F. ANTHONY GRECO

6 vi 8. Lung Cancer Cachexia 125 ROWAN T. CHLEBOWSKI, DAVID HEBER and JEROME B. BLOCK 9. The Neurophysins and Small Cell Lung Cancer 143 WILIAM G. NORTH, L. HERBERT MAURER and JOSEPH F. O'DONNELL 10. The Potential Role of Surgery in the Contemporary Combined Modality Management of Small Cell Anaplastic Lung Cancer 171 ROBERT L. COMIS 11. Chemotherapy and Radiation Therapy of Non-Small Cell Lung Carcinoma KENNETH R. HANDE and ARNOLD W. MALCOLM Subject index 219

7 Foreword to the series Where do you begin to look for a recent, authoritative ar:ticle on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc. Second, by asking eminent authorities in each ofthese areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more. In Cancer Treatment and Research, we have an outstanding group of editors, each having made a major commitment to bring to this new series the very best literature in his or her field. Martinus Nijhoff Publishers has made an equally major commitment to the rapid publication of high quality books, and world-wide distribution. Where can you go to find quickly a recent authoritative article on any major oncology problem? We hope that Cancer Treatment and Research provides an answer. WILLIAM L. MCGUIRE Series Editor

8 Preface Lung cancer remains an extremely difficult neoplasm to treat effectively. A large part of our lack of success in dealing with these patients is related to our empiric therapeutic attempts. Slowly our basic understanding of the lung cancers is improving and techniques are becoming available to allow us to better understand the biology of these neoplasms. This volume reviews several areas of interest in regard to the biologic behavior and characteristics of lung cancer. Chapters deal with the in vitro growth of small cell lung cancer, the investigation of growth factors in human lung cancer, the production of monoclonal antibodies against lung cancer and the application and potential usefulness of the human tumor cloning assay in lung cancer management. These avenues of investigation are likely to establish a more scientific basis on which more rational therapy can be designed. Carney and associates have established several continuous small cell lung cancer cell lines in their laboratory. The amine precursor uptake and decarboxylation (APUD) properties of this neoplasm have been confirmed by demonstrating the presence of neurosecretory granules and high levels of the APUD enzyme L-dopa decarboxylase. In addition, several new markers have been documented including bombesin, creatine-kinase BB and neuronspecific enolase. These tumor products along with others may be useful serum markers in patients with small cell lung cancer. In vitro growth requirements have also been identified in a serum-free chemical medium, the HITES medium. These studies may be close to finding growth inhibitors which are clinically applicable. Preliminary studies reported by Carney et at. also show what appears to be a specific cytogenetic abnormality in small cell lung cancer, a deletion involving chromosome 3 (3p). Such a marker, if confirmed, would not only help to better identify the neoplasm, but would be very helpful in various other studies by providing an accurate in vitro marker.

9 x Sherwin and Todaro review their work with transforming growth factors, a class of peptide growth factors which are produced by lung cancer cells in vitro. It also appears that several patients with advanced cancers, including lung cancer, have detectable tumor-associated transforming growth factors in their urine. The concept of' autocrine secretion' (the secretion of growth factors such as transforming growth factors and often related molecules by tumor cells required for tumor growth and survival in vivo) forms the basis for attempts to manipulate these substances in hopes of preventing or inhibiting tumor growth. Cuttitta and associates discuss their work on the generation and characterization of monoclonal antibodies directed against human lung cancer. Details are reviewed regarding small cell lung cancer antibodies which preferentially bind to tissue culture cell lines and autopsy tissue samples, but not with a variety of autologous cell lines and normal tissues. Although the specific antigen or antigens are not yet identified, several monoclonal antibodies have been used to immunohistochemically stain patients' tumors, to type human tumors and to define various antigenic determinates of small cell lung cancer. The potential of the specific binding properties of monoclonal antibodies may form the basis of useful therapies. Conjugation of antibodies to drugs, radioisotopes or toxic molecules offers the potential for the 'magic bullet'. Callahan et al. review the limitations, applications and potential usefulness of the tumor cloning assay in lung cancer management. The current clinical usefulness is limited by the relatively low growth rate (50%), the time and expense involved and the low plating efficiency even when there is growth. Only a small number of drugs can be tested against most individual tumors since the plating efficiency is often low, and the results obtained take about two weeks. However, the system is being refined and of those tumors with adequate growth the prediction of in vivo tumor response has been good, particularly for predicting drug resistance. Although the determination of in vitro drug sensitivity appears to be in the 'infancy period', it will continue to grow and develop. Other contributors to this volume deal with the problem of accurate histologic diagnosis in poorly differentiated lung cancers, the riddle of cachexia associated with lung cancer, the morphologic alterations of small cell lung cancer following intensive therapy, and the promise of the neurophysins as reliable biochemical small cell lung cancer markers. Two novel and potentially useful therapeutic strategies are reviewed: the use of adjuvant surgery in patients with limited stage small cell lung cancer and the use of high-dose chemotherapy with autologous bone marrow transplantation. Finally, a comprehensive review of therapeutic attempts in advanced non-small cell lung cancer is presented.

10 The majority of the work presented in this volume deals with new areas of clinical and basic research of the lung cancer problem. The contributors to this volume represent a small number of the many interested investigators who will eventually help to find the necessary answers. F. ANTHONY GRECO Xl

11 List of Contributors BLOCK, Jerome B., M.D., University of California, Los Angeles School of Medicine, Department of Medicine, Harbor-UCLA Medical Center, Division of Medical Oncology, Torrance, CA 90509, USA. CALLAHAN, S. Kent, M.D., Department of Medicine, University of Texas, Health Science Center, San Antonio, TX 78284, USA. CARNEY, Desmond N., M.D., NCI-Naval Medical Oncology Branch, National Naval Medical Center, Bethesda, MD 20814, USA. CHLEBOWSKI, Rowan T., M.D., Ph.D., University of California, Los Angeles School of Medicine, Department of Medicine, Harbor-UCLA Medical Center, Division of Medical Oncology, Torrance, CA 90509, USA. COLTMAN, Charles A. Jr., Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78284, USA. COM IS, Robert L, M.D., Associate Professor of Medicine, Chief, Section of Medical Oncology, Department of Medicine, State University of New York, Upstate Medical Center, 750 East Adams ~treet, Syracuse, NY 13210, USA. CUTTITTA, Frank, M.D., NCI-Naval Medical Oncology Branch (DCT INCI/NIH) and Litton Bionetics, National Naval Medical Center, Bethesda, MD 20814, USA. FER, Mehmet F., M.D., Assistant Professor, Department of Medicine, Division of Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. GAZDAR, Adi F., M.D., NCI-Naval Medical Oncology Branch (DCT/NCIINIH) National Naval Medical Center, Bethesda, MD 20814, USA. GRECO, F. Anthony, M.D., Associate Professor, Department of Medicine, Director, Division of Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. GROSH, William W., M.D., Research Fellow, Department of Medicine,

12 XIV Division of Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. HANDE, Kenneth R., M.D., Nashville Veterans Administration Medical Center and Division Medical Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. HEBER, David, M.D., Ph.D., University of California, Los Angeles School of Medicine, Department of Medicine, Harbor-UCLA Medical Center, Divisions of Endocrinology and Metabolism, Torrance, CA 90509, USA. KITTEN, Cliff, M.D., Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78284, USA. LUKEMAN, John M., M.D., The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Department of Pathology, Houston, TX 77030, USA. MACKAy, Bruce, M.D., Ph.D., The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Department of Pathology, Houston, TX 77030, USA. MALCOLM, Arnold W., M.D., Nashville Veterans Administration Medical Center and Division of Radiology, Vanderbilt University School ofmedicine, Nashville, TN 37232, USA. MAURER, L. Herbert, M.D., Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA. MINNA, John D., M.D., NCI-Naval Medical Oncology Branch (DCT/NCIINIH) National Naval Medical Center, Bethesda, MD 20814, USA. NORTH, William G., M.D., Department of Physiology, Dartmouth Medical School, Hanover, NH 03755, USA. O'DONNELL, Joseph F., M.D., Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA. OlE, Herbert K., M.D., NCI-Naval Medical Oncology Branch (DCT/NCIINIH) and Litton Bionetics, National Naval Medical Center, Bethesda, MD 20814, USA. ROSEN, Steven, M.D., NCI-Naval Medical Oncology Branch, National Naval Medical Center, Bethesda, MD 20814, USA. SHERWIN, Stephen A., M.D., Biological Response Modifiers Program, National Cancer Institute, Frederick, MD 21701, USA. TODARO, George 1., M.D., Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21701, USA. VON HOFF, Daniel D., M.D., Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78284, USA. WOLFF, Steven N., M.D., Division of Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.