PREFACE - Principles of Cancer Biotherapy

The idea for the first edition of Principles of Cancer Biotherapy was formulated in the early 1980s.  As the founding director of the Biological Response Modifiers Program for the National Cancer Institute from 1980-1984, one of us (rko) envisioned a textbook that would embody the principles of the then fledgling fourth modality of cancer treatment - biotherapy.  Contributing authors were solicited in 1985, and the first edition came off the presses in 1987.  Principles represented the first comprehensive textbook on the use of cancer biotherapy and summarized the work done in this field through 1986.

The second edition of Principles was published in 1991 about the time biotherapy was more broadly recognized as the fourth major cancer treatment modality.  Subsequent textbooks by DeVita, Hellman and Rosenberg [1] in 1991, Mitchell [2] in 1993 and Rosenberg [3] in 2000 validated the importance of this modality in cancer care.

This third edition was published in 1998 and confirmed the tremendous progress that had been made in the previous five years using biologicals in cancer treatment.  It was generally agreed that biopharmaceuticals were producing major opportunities for new cancer therapies.  Cancer biotherapy was emerging as a more specific and targeted form of systemic cancer treatment.  Cancer growth control was also becoming an effective method of treatment complementing cancer destruction as mechanisms of cancer treatment and “cure”.

The fourth edition of Principles was published in 2003. It was apparent that biotherapy and the use of biopharmaceuticals had not only become recognized as the fourth modality of cancer treatment, it was clear that biopharmaceuticals had become the dominant form of new cancer therapeutics which in the future will replace less selective, more toxic forms of therapy.

For years, the chemical manipulation of small molecules has been pursued in drug development.  We now have all the tools for the biological manipulation of natural substances for therapeutic use.  In fact, as we better understand the interaction between biological molecules and their receptors, it is clear that biological manipulation and chemical manipulation are coming together to bring molecular medicine to the bedside.  Many biological molecules are large and have functions other than those mediated by their active sites.  There is increasing evidence that drug development will focus on the interaction between the smaller active regions of these large biological molecules and their receptors.  This opens up a broad field of molecular design for extending and improving the therapeutic activities of natural biological molecules.  This has recently been extended to small molecules interacting with DNA/RNA (anti-sense), with enzymes such as tyrosine kinase and with growth and vascular factor receptors.  The last decade has been extraordinarily productive  in the development of new anticancer drugs through chemical and biological manipulation of these natural molecules.  Thus, the body itself has become the “medicine cabinet” of the future.

In the 1990s and beyond into the next millennium, medicine will face extraordinary demands.  While technology brings us tremendous opportunity, it also highlights problems in our medical care system.  Most new technology is expensive and, as it comes from the laboratory to the clinic, is by its very nature untried and unproven.  Our medical care system involves a private and government insurance reimbursement system that favors paying for marginally effective medical care of the past rather than innovative medical treatments of the future. Such a system is inhibitory to the development of effective new anti-cancer medicines.

To more rapidly and efficiently exploit the opportunities in cancer biotherapy in the future, patients, employers, insurers, universities, and government must come together and redefine the system of reimbursement to maximize the patient’s opportunity for access to new and potentially effective cancer therapies.  To simply reimburse for old ineffective or marginally effective treatment is not the answer.  Provisions must be made to fund clinical research and afford these new approaches broader use at the bedside.  We must develop methods to allow our patients access to the opportunities of the future, while maintaining solid support for effective therapies of the past.  No longer is it acceptable to pay only for medical care that utilizes old technology, such as chemotherapy, that is approved but only marginally effective.  Across the broad spectrum of human malignancies, most chemotherapeutic drugs are toxic and of limited medical value.  We must support clinical research in its efforts to bring newer methods of cancer treatment to the clinic, methods that are less toxic and more effective.

We believe cancer biotherapy will ultimately replace much of what we utilize today in cancer treatment.  In light of this view, we want to thank all the authors for their dedication to purpose in writing this fifth edition of Principles. This book summarizes an evolving science and a rapidly changing medical practice.  As we progress into the millennium, it now becomes possible to envision a much more diversified system of cancer research and treatment that will afford greater opportunities for our patients.  As indicated in some of the chapters in Principles, there is increasing evidence that our historical “kill and cure” outlook in cancer treatment is in need of modification.  Some forms of cancer biotherapy use the strategy of tumor growth stabilization and control through continued biological therapy over a longer period of time, akin to the use of insulin in the treatment of diabetes.  These chapters illustrate some of these new methods of thinking and illustrate new strategies for the treatment and control of cancer.  It is always difficult to move from past dogmas to future opportunities, but this fifth edition of Principles of Cancer Biotherapy illustrates why it is so important for researchers, regulators and clinicians to explore and apply these new opportunities in cancer biotherapy to the benefit of our patients.

Robert K. Oldham, M.D.
Robert O. Dillman MD

REFERENCES

1. DeVita VT Jr, Hellman S, Rosenberg SA. Biologic Therapy of Cancer. J.B. Lippincott, 1991.

2. Mitchell MS. Biological Approaches to Cancer Treatment. McGraw-Hill, 1993.

3. Rosenberg SA. Principles and Practices of the Biologic Therapy of Cancer. J.B. Lippincott, 2000.