BIOLOGICAL BASIS OF GERIATRIC ONCOLOGY

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BIOLOGICAL BASIS OF

GERIATRIC ONCOLOGY

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Cancer Treatment and Research

Steven T. Rosen, M.D., Series Editor

Sugarbaker, P. (ed): Peritoneal Carcinomatosis: Drugs and Diseases. 1995. ISBN 0-7923-3726-3.

Sugarbaker, P. (ed): Peritoneal Carcinomatosis: Principles of Management. 1995. ISBN 0-7923-3727-1.

Dickson, R.B., Lippman, M.E. (eds.): Mammary Tumor Cell Cycle, Differentiation and Metastasis.

1995. ISBN 0-7923-3905-3.

Freireich, E.J, Kantarjian, H.(eds):Molecular Genetics and Therapy of Leukemia. 1995. ISBN 0-7923-3912-6.

Cabanillas, F., Rodriguez, M.A.(eds): Advances in Lymphoma Research. 1996. ISBN 0-7923-3929-0.

Miller, A.B. (ed.): Advances in Cancer Screening. 1996. ISBN 0-7923-4019-1.

Hait, W.N. (ed.): Drug Resistance. 1996. ISBN 0-7923-4022-1.

Pienta, K.J. (ed.): Diagnosis and Treatment of Genitourinary Malignancies. 1996. ISBN 0-7923-4164-3.

Arnold, A.J. (ed.): Endocrine Neoplasms. 1997. ISBN 0-7923-4354-9.

Pollock, R.E. (ed.): Surgical Oncology. 1997. ISBN 0-7923-9900-5.

Verweij, J., Pinedo, H.M., Suit, H.D. (eds): Soft Tissue Sarcomas: Present Achievements and Future Prospects. 1997. ISBN 0-7923-9913-7.

Walterhouse, D.O., Cohn, S. L. (eds.): Diagnostic and Therapeutic Advances in Pediatric Oncology.

1997. ISBN 0-7923-9978-1.

Mittal, B.B., Purdy, J.A., Ang, K.K. (eds): Radiation Therapy. 1998. ISBN 0-7923-9981-1.

Foon, K.A., Muss, H.B. (eds): Biological and Hormonal Therapies of Cancer. 1998. ISBN 0-7923-9997-8.

Ozols, R.F. (ed.): Gynecologic Oncology. 1998. ISBN 0-7923-8070-3.

Noskin, G. A. (ed.): Management of Infectious Complications in Cancer Patients. 1998. ISBN 0-7923-8150-5.

Bennett, C. L. (ed.): Cancer Policy. 1998. ISBN 0-7923-8203-X.

Benson, A. B. (ed.): Gastrointestinal Oncology. 1998. ISBN 0-7923-8205-6.

Tallman, M.S., Gordon, L.I. (eds): Diagnostic and Therapeutic Advances in Hematologic Malignancies.

1998. ISBN 0-7923-8206-4.

von Gunten, C.F. (ed): Palliative Care and Rehabilitation of Cancer Patients. 1999. ISBN 0-7923-8525-X Burt, R.K., Brush, M.M. (eds): Advances in Allogeneic Hematopoietic Stem Cell Transplantation. 1999.

ISBN 0-7923-7714-1.

Angelos, P. (ed.): Ethical Issues in Cancer Patient Care 2000. ISBN 0-7923-7726-5.

Gradishar, W.J., Wood, W.C. (eds): Advances in Breast Cancer Management. 2000. ISBN 0-7923-7890-3.

Sparano, Joseph A. (ed.): HIV & HTLV-I Associated Malignancies. 2001. ISBN 0-7923-7220-4.

Ettinger, David S. (ed.): Thoracic Oncology. 2001. ISBN 0-7923-7248-4.

Bergan, Raymond C. (ed.): Cancer Chemoprevention. 2001. ISBN 0-7923- 7259-X.

Raza, A., Mundle, S.D. (eds): Myelodysplastic Syndromes & Secondary Acute Myelogenous Leukemia 2001.

ISBN: 0-7923-7396.

Talamonti, Mark S. (ed.): Liver Directed Therapy for Primary and Metastatic Liver Tumors. 2001.

ISBN 0-7923-7523-8.

Stack, M.S., Fishman, D.A. (eds): Ovarian Cancer. 2001. ISBN 0-7923-75 0-0.

Bashey, A., Ball, E.D. (eds): Non-Myeloablative Allogeneic Transplantation. 2002. ISBN 0-7923-7646-3.

Leong, Stanley P.L. (ed.): Atlas of Selective Sentinel Lymphadenectomy for Melanoma, Breast Cancer and Colon Cancer. 2002. ISBN 1-4020-7013-6.

Andersson , B., Murray D. (eds): Clinically Relevant Resistance in Cancer Chemotherapy. 2002.

ISBN 1-4020-7200-7.

Beam, C. (ed.): Biostatistical Applications in Cancer Research. 2002. ISBN 1-4020-7226-0.

Brockstein, B., Masters, G. (eds): Head and Neck Cancer. 2003. ISBN 1-4020-7336-4.

Frank, D.A. (ed.): Signal Transduction in Cancer. 2003. ISBN 1-4020-7340-2.

Figlin, Robert A. (ed.): Kidney Cancer. 2003. ISBN 1-4020-7457-3.

Kirsch, Matthias; Black, Peter McL. (ed.): Angiogenesis in Brain Tumors. 2003. ISBN 1-4020-7704-1.

Keller, E.T., Chung, L.W.K. (eds): The Biology of Skeletal Metastases. 2004. ISBN 1-4020-7749-1.

Kumar, Rakesh (ed.): Molecular Targeting and Signal Transduction. 2004. ISBN 1-4020-7822-6.

Verweij, J., Pinedo, H.M. (eds): Targeting Treatment of Soft Tissue Sarcomas. 2004. ISBN 1-4020-7808-0.

Finn, W.G., Peterson, L.C. (eds.): Hematopathology in Oncology. 2004. ISBN 1-4020-7919-2.

Farid, N., (ed): Molecular Basis of Thyroid Cancer. 2004. ISBN 1-4020-8106-5.

Balducci, L., Extermann, M. (eds.): Biological Basis of Geriatric Oncology. 2004. ISBN Leong, Stanley P.L., Kitagawa, Y., Kitajima, M. (eds.): Selective Sentinel Lymphadenectomy for Human Solid Cancer 2005. ISBN 0-387-23603-1

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BIOLOGICAL BASIS OF GERIATRIC ONCOLOGY

edited by

LODOVICO BALDUCCI, MD Professor of Oncology and Medicine University of South Florida College of Medicine Program Leader, Senior Adult Oncology Program H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, USA

MARTINE EXTERMANN, MD, PhD Associate Professor of Oncology and Medicine University of South Florida College of Medicine

Senior Adult Oncology Program

H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida, USA

Springer

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eBook ISBN: 0-387-23962-6 Print ISBN: 0-387-23961-8

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FOREWORD

The population of Western countries is aging, and cancer in older aged persons is becoming increasingly common. The management of these neoplasms is a novel problem. Direct information on the outcome of cancer prevention and of cytotoxic chemotherapy in older individuals is scarce, especially for those aged 80 and over, and it is not clear whether the same process should direct medical decisions in younger and older persons. It is reasonable to assume that the benefits of cancer prevention and treatment diminish and the dangers increase with age. The expected gains from cancer treatment may be lessened by shorter life expectancy. The risk of therapeutic complications may be increased and the consequences of these complications may become more serious due to limited functional reserve of multiple organ-systems, and fading social support and economic resources. In addition, the biology of cancer may change with the age of the patient, due to a series of events that have been clarified only in part. For example, the prevalence of Multidrug Resistance in Acute Myelogenous Leukemia is much higher for patients over 60, which make the treatment less effective and the risk of treatment-related deaths higher. At the same time, the risk of local recurrence of breast cancer after partial mastectomy declines with age, indicating a more indolent disease.

Several publications, including books, review articles and original studies, related to cancer in the elderly have appeared during the last ten years and have highlighted important points that have become widely accepted:

Age by itself is not and should never be a contraindication to cancer management, including prevention and treatment.

The management of cancer in the older person should be individualized according to individual life expectancy, treatment tolerance, and risk of experiencing the complications of cancer including death, disability, and discomfort.

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A number of simple provisions may ameliorate the complications of cytotoxic chemotherapy and allow the administration of full doses of treatment. These provisions include prophylaxis of neutropenic infections, avoidance of severe anemia, timely management of mucositis, and provision of adequate home care giving.

The practical application of these directions remains somehow controversial however, as the methods to estimate life expectancy, functional reserve, and tumor behavior are poorly defined. The main goal of this book is to provide a simple blueprint enabling the practitioners of oncology, geriatrics, and primary care to decide when a patient may or may not benefit from cancer prevention and treatment. Based on the current knowledge of the biology of aging and cancer, the books examines several facets of patient assessment, including function, comorbidity, physical performance and laboratory tests, as well as the way these different forms of assessment may be integrated in medical decisions. At the meantime, the book explores future possibilities for understanding the interaction of aging and cancer biology and for predicting these interactions, and provides a rationale for clinical trials of chemoprevention of cancer in the older person by unraveling the mechanisms that associate aging and carcinogenesis. Some of these mechanisms, including the genomic changes of age, are predictable, while others, including proliferative senescence, are counter-intuitive, and open new, unsuspected opportunities for intervention. Aware of the rapid evolution of the field, we wanted for this book to become an expandable and adaptable frame of reference, able to accommodate new information and still able to direct the practitioner in the management of older individuals even when the current information will be outdated. The emphasis on current research directions in the biology of aging, of cancer, and of the hemopoietic system that is intimately connected to the management of cancer, should make the reader attuned to new developments and allow the reader to rapidly incorporate these developments into clinical thinking.

Another important goal of this book is to highlight the important lessons coming from the study of aging that may be collapsed into two points:

To a large extent, the study of aging involves a movement from the bedside to the bench, which is directly opposed to the current trend of oncology. As underlined in the initial chapter, epidemiology is the main clue to the biological interactions of cancer and aging:

epidemiology and clinical observation are still the main source for experimental hypothesis.

Due to the scarcity of information, the study of geriatric oncology requires acceptance of some degree of uncertainty. In clinical practice this involves attention to unexpected and unpredictable occurrences; in clinical trials this involves readiness to accommodate a number of unknown parameters.

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The best opportunity for real progresses in the field may come from the integration of these points in clinical practice and clinical research.

The third and final goal of this book is to provide an updated and practical research handbook for the increasingly large host of young investigators who want to become involved in the field. The need for such handbook is revealed by a number of recent initiatives aimed to promote research in geriatric oncology. Among them we would like to highlight the issuance of a RFA for program grants in geriatric oncology by a combined NCI/NIA effort, and the institution of a number of fellowships in geriatric oncology through a grant of the Hartford Foundation to the American Society of Clinical Oncology.

In addition to all excellent collaborators of the book, we would like to thank the numerous friends and colleagues who have been engaged with us in this adventure of geriatric oncology during the last ten years, and in particular, we would like to acknowledge the leadership of Rosemary Yancik, Ph.D., who single-handedly generated the field more than two decades ago, and the members of the Senior Adult Oncology Program at the H. Lee Moffitt Cancer Center, to whom this book is dedicated.

Lodovico Balducci M.D.

Martine Extermann M.D. Ph.D.

BIOLOGICAL BASIS OF GERIATRIC ONCOLOGY

BIOLOGICAL BASIS OF

GERIATRIC ONCOLOGY

Cancer Treatment and Research

BIOLOGICAL BASIS OF GERIATRIC ONCOLOGY

edited by

LODOVICO BALDUCCI, MD Professor of Oncology and Medicine University of South Florida College of Medicine Program Leader, Senior Adult Oncology Program H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, USA

MARTINE EXTERMANN, MD, PhD Associate Professor of Oncology and Medicine University of South Florida College of Medicine

Senior Adult Oncology Program

H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida, USA

CONTENTS

FOREWORD