Cytokine Therapy

The British Medical Journal (BMJ) is distributed, at no extra charge, at weekly intervals to all members of the British Medical Association. It is therefore the most widely read journal by doctors with a spectrum of readers varying from general practitioners to hospital consultants in all specialities. This book represents a compilation of a series of review articles published in the BMJ in 1992 whose aim was to examine the present state of management of a number of malignancies. It also attempts to increase understanding of the biology of these diseases, their treatment and their impact on people. Since the treatment of patients with cancer requires a broad approach, and usually involves interaction between many doctors of differing backgrounds, a series of review articles in a general medical journal is timely. The level at which such a series of articles should be pitched is perhaps somewhat more problematic. The book contains chapters ranging from the common malignancies of lung, breast and colo-rectum to current issues in biological therapy, molecular genetics, and quality of life. It was a pleasure to see a useful contribution relating to radiotherapy often sadly and inappropriately neglected in such a book, for a modality of therapy that is utilised in up to 50% of patients with cancer. Perhaps inevitably, half of the book is taken up with reviews of unusual but curable tumours including testicular cancer, Hodgkin's disease and non-Hodgkin's lymphoma. The thrust of each chapter is not consistent and tends to reflect the special interests of the author. In general however, the information provided is well written, readily understandable and enumerates the current status of general principles of cancer treatment. There is appropriate detail of important major developments in common cancers such as implementation of adjuvant therapy in high risk patients with rectal and colonic carcinoma, and also confirmation of the benefit of adjuvant therapy in the management of early breast cancer derived from a recent meta-analysis. One notable chapter is by Maurice Slevin regarding quality of life, implicitly recognised as an important measure that should be assessed in most cancer trials, particularly where treatments are given with palliative intent. Currently palliative therapy is often delayed until the onset of significant symptoms. Dr Slevin advances the perhaps unfashionable view that more efficacious, even if substantially more toxic, palliative treatment given earlier may be of benefit. I do however take issue with the statement on the …

The British Medical Journal (BMJ) is distributed, at no extra charge, at weekly intervals to all members of the British Medical Association. It is therefore the most widely read journal by doctors with a spectrum of readers varying from general practitioners to hospital consultants in all specialities. This book represents a compilation of a series of review articles published in the BMJ in 1992 whose aim was to examine the present state of management of a number of malignancies. It also attempts to increase understanding of the biology of these diseases, their treatment and their impact on people. Since the treatment of patients with cancer requires a broad approach, and usually involves interaction between many doctors of differing backgrounds, a series of review articles in a general medical journal is timely. The level at which such a series of articles should be pitched is perhaps somewhat more problematic.
The book contains chapters ranging from the common malignancies of lung, breast and colo-rectum to current issues in biological therapy, molecular genetics, and quality of life. It was a pleasure to see a useful contribution relating to radiotherapy often sadly and inappropriately neglected in such a book, for a modality of therapy that is utilised in up to 50% of patients with cancer. Perhaps inevitably, half of the book is taken up with reviews of unusual but curable tumours including testicular cancer, Hodgkin's disease and non-Hodgkin's lymphoma. The thrust of each chapter is not consistent and tends to reflect the special interests of the author. In general however, the information provided is well written, readily understandable and enumerates the current status of general principles of cancer treatment. There is appropriate detail of important major developments in common cancers such as implementation of adjuvant therapy in high risk patients with rectal and colonic carcinoma, and also confirmation of the benefit of adjuvant therapy in the management of early breast cancer derived from a recent metaanalysis. One notable chapter is by Maurice Slevin regarding quality of life, implicitly recognised as an important measure that should be assessed in most cancer trials, particularly where treatments are given with palliative intent. Currently palliative therapy is often delayed until the onset of significant symptoms. Dr Slevin advances the perhaps unfashionable view that more efficacious, even if substantially more toxic, palliative treatment given earlier may be of benefit. I do however take issue with the statement on the back cover that 'rarer diseases such as Hodgkin's lymphoma may act as models for research in other cancers'. Such an approach has been tried over the last 30 years. Surely the fact that the mortality rates for common malignancies such as breast cancer have remained stubbornly stable in spite of improved public education, and the wider more rational prescribing of adjuvant therapy, should render such statements outmoded. A chapter on cancer treatment in the year 2020 should have stimulated some interesting and useful debate, as it seems likely that increased understanding of molecular/cellular biology should lead to a major conceptual shift in cancer management, as suggested in the chapter on molecular genetics by Bruce Ponder.
As a whole the book is somewhat diverse, and it is not entirely clear to me who would wish to buy it. For the specialist it is too general and no doubt many general practitioners would consider it too specialised! When I first saw these articles as they appeared in the BMJ I thought they worked rather well, but as a book I am not so sure.
The first biological response modifiers to reach patients were unlike any anticancer drugs previously tested. Intense public interest was aroused, but initial enthusiasm was replaced by crashing disappointment after reports of serious toxicities. This book seeks to provide a balanced overview of the cytokines now entering clinical practice.
Nine cytokines are presented in concise chapters: erythropoietin, granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukins-1, -2 and -3, interferons alpha and gamma, and tumour necrosis factor. A final chapter explores the complexities of the cytokine network. An international panel of contributors, mainly haematologists, describe the molecular and biological properties of each cytokine before discussing the clinical trial experience. Their assessments range from euphoric to sceptical. For example, there is an interesting contrast in the approaches of Takaku (describing G-CSF) and Khwaja and Linch (describing GM-CSF). These two drugs are now being marketed for the same indication, to reduce the severity of neutropenia and neutropenic sepsis after cytotoxic chemotherapy. The former expects G-CSF treatment after chemotherapy 'to become standard therapy for cancer patients in the very near future' whereas the latter feel that GM-CSF 'cannot be recommended . . . in association with conventional chemotherapy' and 'it is still not clear whether (its use) is justifiable on a routine basis' after bone marrow transplantation.
The most successful chapters are those on erythropoietin, GM-CSF and alpha interferon which are the best characterised cytokines and have an established clinical role. There are descriptions of their use in renal failure and viral hepatitis in addition to their applications in cancer treatment.
The chapters on interleukins-1 and -3 and gamma interferon are well balanced, despite these cytokines being in a relatively early stage in development and the uncertainty about their clinical role.
The editors have sought to provide for their clinical colleagues an approachable and easily digestible account of those cytokines presently in clinical use. The chapters inevitably differ in their palatability, but each is readily consumed at a single sitting. I think it will be read with benefit by senior clinicians, junior doctors and other ward staff involved in cytokine therapy. It does not however constitute a guide to clinical practice. The section on interleukin-2, for example, fails to describe the life-threatening toxicities such as capillary leak syndrome that necessitated intensive care of early patients. Graduate students and research fellows have been better served by the comprehensive and consistent 'Cytokines in Cancer Treatment' by Franni Balkwill (1989).
In a fast moving field such as cytokine research, any account will be incomplete. This book provides a sharp image of the cytokines now registered for treatment and a snapshot of those currently undergoing clinical evaluation. P.J. Woll