- Paediatric Haematology
- Chemotherapy Clinical Trials
- Cancer Council Victoria & Victorian Cooperative Oncology Group
As a young physician training in London in 1938, Dr John Colebatch saw his first case of childhood leukaemia, a condition with a cruel image because it was invariably fatal within months of diagnosis. He learned to perform marrow puncture of the sternum, the flat narrow bone in the front of the chest, and undertook a project to determine the normal bone marrow profile of 50 infants and children in good health.
After returning to Australia from wartime duties, he started clinical work in Melbourne and quickly put his knowledge of bone marrow and its disorders to work. In 1946, he treated the first of what turned out to be 100s of patients with childhood leukaemia, ordering a blood transfusion to ease the distressing symptoms.
A few years later he read reports of new drug treatments that extended the lives of leukaemia patients from about 3 months to 5 months or more after diagnosis. In 1948, he started working with these treatments, which reduced complications of the disease rather than dealing with leukaemia’s immediate effects on the bone marrow.
This was a time of rapid pharmaceutical development and within a few years new types of drugs were available that attacked the abnormal white blood cells characteristic of leukaemia. Dr Colebatch was one of the first physicians in Australia to prescribe the new treatments, collectively known as chemotherapy. Although he regarded their use in leukaemia as a major advance, he wanted to find out which chemicals, in what dose, and for what duration could bring about an improvement of symptoms in his patients most reliably. At that stage, the idea of producing a remission and curing children of their leukaemia seemed a distant hope.
The chemical therapies were difficult treatments for all concerned, involving numerous blood tests, an ever-present threat of serious side effects arising from severe bone marrow damage, and meticulous record and data handling. In seeking the consent of parents to allow the treatment, Dr Colebatch spoke along these lines:
‘This treatment is new — a man in America says it’s producing improved results. He hasn’t claimed any cures but you’ve got to start somewhere — you never know, they may be curing someone in a couple of years' time. We can do the same thing here now and it will involve a lot of blood tests and so on, but not an operation as a rule — nothing more serious’.
Dr Colebatch’s efforts were controversial and raised ethical concerns which have since recurred with other chemotherapeutic agents. Was it preferable to continue with the existing approach of providing symptom relief and allowing nature to take its course, or should attempts be made to prolong life with the ultimate aim of a cure, even though until that goal was reached many patients would die after a short reprieve and substantial discomfort?
During 1957, Dr Colebatch discussed his work informally at the Saturday medical seminars, organised by Dr EV ‘Bill’ Keogh, medical adviser to the Cancer Council, at the University of Melbourne medical school. Dr Keogh’s interest in the statistics of cancer was evident in his use of Cancer Council Cancer Registry data to begin proceedings at such seminars, enabling him to provide statistical profiles of cancer incidence by site that formed the main subject of most meetings.
Dr Colebatch convinced some doctors about the value of chemotherapy in childhood leukaemia while others remained uncertain. By 1959, there was definite evidence that chemotherapy was prolonging life by months and sometimes years. He successfully applied for a Cancer Council research Grant-in-aid to facilitate a clinical study at the Royal Children’s Hospital involving all children admitted with leukaemia. The following year he achieved his first long-term relapse — which, in retrospect, was a cure.
He had an opportunity to gauge world thinking on chemotherapy for childhood leukaemia and other cancers in 1962 when he was awarded the Cancer Council’s Robert Fowler Travelling Fellowship. During a period of three-and-a-half months he visited centres in Europe, America, Asia and New Zealand and studied the US National Cancer Institute’s approach to organising studies in multiple research centres.
Flushed with enthusiasm about promising new drug therapies and new approaches to drug administration, he applied for, and won, Australian Cancer Society support for a trial of chemotherapy in childhood leukaemia involving 15 paediatric hospitals and departments nationwide. The ACS-sponsored trial proved to be a milestone in Australian medical history, being the first formal randomised clinical trial of any kind conducted nationally. The study compared the outcome for patients with acute leukaemia when given four drugs in sequence in two different ways (cyclic versus non-cyclic administration). It showed that the drug vincristine could maintain remission. Furthermore, it aroused professional interest in cooperative clinical trials.
In 1967, Dr Colebatch was appointed the Cancer Council’s inaugural W J Kilpatrick Cancer Research Fellow. His subsequent overseas travels convinced him of the need to create multidisciplinary clinics to improve the treatment of childhood leukaemia. It took 10 months to establish the Haematology Research Unit at the Royal Children’s Hospital, but the effort was well worthwhile. The duration of remissions increased and the general comfort of the children also improved.
The unit was soon involved in six linked studies of chemotherapy for leukaemia and a study of the impact of radiotherapy to prevent or limit infiltration of leukaemia into the brain and spinal cord. By 1972, it was clear that almost all the drugs capable of destroying leukaemic cells achieved their treatment effect mainly by their action on one or more phases of the leukaemic cells’ generation cycle. This understanding of the underlying process of chemotherapy opened up the possibility of timing drug administration optimally to achieve maximum cytotoxic effect.
By 1973, doctors were inducing cells to enter the cycle in which they could be damaged or destroyed most readily and were synchronising chemotherapy with this most vulnerable part of the cell generation cycle. By the following year, they could advise with increased confidence when particular patients could come off their chemotherapy having been disease-free for a number of years. Not surprisingly, the Haematology Research Unit was used as a model by other Australian hospitals involved in chemotherapy research.
Studies such as those Dr Colebatch helped establish broke new ground in chemotherapy, radiotherapy and immunological therapy and highlighted the need for improved training of doctors in emerging cancer treatment methods. In response, the Cancer Council’s Medical and Scientific Committee established in March 1976 a sub-committee whose brief was to explore all aspects of the development of clinical oncology. Three months later, the Victorian Chemotherapy Cooperative Group (VCCG) was established under the Chairmanship of Dr Doug Pearce, with Dr Colebatch appointed the inaugural Executive Secretary in 1977. It emphasised cooperation in the development of chemotherapy — which was still regarded as an experimental method of cancer treatment in Australia.
In 1977, Melbourne haematologist Dr Max Whiteside was appointed VCCG Chairman. He and Dr Colebatch worked to establish a Breast Study Committee (renamed the Breast Cancer Committee), which advised, assisted and coordinated the running of chemotherapy studies for breast cancer. Once again, Dr Colebatch’s experience with childhood leukaemia came into its own, for all the most effective drugs for breast cancer had been used for some years to treat acute leukaemia. Drs Whiteside and Colebatch also helped establish a Head and Neck Protocol Sub-Committee (1977-1978), which investigated the place of pre and post-operative chemotherapy in head and neck cancers; a Lung Cancer Study Group (1978-1982) to exchange information on methods and treatment results; and the Gastrointestinal Study Committee in 1979 (renamed the Gastrointestinal Cancer Committee) to act as a central coordinator of measures for improving the standard of treatment, and to disseminate information on the wider aspects of gastrointestinal cancer control.
Dr Colebatch oversaw in 1977 the formation of the Cancer Council’s Clinical Trials Secretariat (which developed into the Centre for Clinical Research in Cancer) to help the VCCG committees with detailed planning of trial protocols, form design, collection, monitoring and analysis of clinical data and the administration and organisation of meetings. He also steered the sub-committee to review chemotherapeutic oncology services in Victoria in 1978, which was adopted by the Health Services Commission in 1982..
A name change in 1981 to the Victorian Cooperative Oncology Group (VCOG) signalled a widening of interest beyond chemotherapy to all aspects of cancer treatment, and associated medical education.
Extracted from “Gaining Ground against Cancer, Anti-Cancer Council of Victoria 1936-1996”
Ann Westmore PhD, published by Cancer Council Victoria 2005
Dr Colebatch retired from the role of VCOG Executive Secretary (succeeded by Professor Richard Lovell) in 1982, but remained as a consultant to the VCOG and Cancer Council Victoria for many years. In his consultancy role, he provided sound advice on clinical trial practice procedures, particularly in the development and conduct of the COSA-UK-NZ Endometrial Cancer Trial E1/82, initiated by Victoria’s gynaecological oncology community.
In addition to his activities in Victoria, Dr Colebatch was also involved in a number of national and international cancer organisations. These included the Clinical Oncological Society of Australia (Inaugural Chair of Paediatric Group, Member of Council, Member of Standing Committee on Anti-Cancer Medications, Member of Standing Committee on Clinical Trials, Member of Steering Committeee for National Data Centre), Haematological Society of Australia (Foundation Member, Vice-President), National Health and Medical Research Council (Regional Grants Committee Member, Haematology-oncology Research Referee Assessor).
The Cancer Council Victoria is proud to announce it has established a five-year Clinical Research Fellowship in honour of Dr John Houghton Colebatch AO.
Dr John Colebatch will be remembered for his pioneering clinical research in paediatric haematology in Victoria and in establishing a firm foundation for good clinical research practice.