Fifty Years of Progress Against Cancer
irradiation with results that have made a real impact on the management of this disease and have prolonged survival.12,13
One of
these trials established the role of prophylactic cranial irradiation in advanced stage small cell lung cancer leading the way in the prevention of brain metastases, while the other trial determined the standard dose of prophylactic irradiation to be delivered to the brain.
Optimisation of Existing Cancer Treatments Optimising treatments for patients with cancer has always been a central objective of the work of the EORTC.
In 1989, pioneering work in the field of organ preservation led to a larynx preservation strategy in patients with hypopharyngeal cancer.14 Overall survival rates were similar for this larynx preservation strategy and conventional total laryngectomy treatment, while allowing two-thirds of patients to retain their larynx.
In successive clinical trials conducted over more than 50 years, continuous progress has been registered in the development of treatment strategies for Hodgkin’s lymphoma.15
These trials have not
only improved treatment efficacy, they have also identified clinical and biological parameters that could be used to adapt the treatment strategy. Because patients enrolled in these EORTC clinical trials were followed-up on a regular basis until death, analysis of the fate of patients after each successive specific treatment has been used to develop strategies that maximise the yield of long-term responses and minimise short- and long-term toxicities in subsequent trials (see Figure 1).
The greatly improved outcomes brought about by the initial trials meant that later trials could aim mainly at reducing (late) treatment toxicity while maintaining excellent disease control. For example, restricting radiotherapy to the involved node was developed for patients with early stage Hodgkin’s lymphoma. Moreover, the growing evidence of late effects following radiotherapy also acted as a spur to reduce doses of radiation as much as possible.16
The introduction of a new and significantly more efficient therapy in the treatment of childhood lymphoid malignancies was the result of an EORTC trial.17
Figure 1: European Organisation for Research and Treatment Hodgkins Lymphoma Trials
100
70 80 90
60 50 40 30 20 10
0 H1 H2 H5 Event Free Survival H6 H7 Overall Survival
Survival in Six Consecutive Hodgkin Lymphoma Trials, trials H1, H2, H5, H6, H7 and H8. Source: Raemaekers J, Kluin-Nelemans H, Teodorovic I, et al., The achievements of the EORTC Lymphoma Group, Eur J Cancer, 2002;38:S107–S113.
is enhanced through the use of mitoxantrone or idarubicin instead of daunorubicin.21
The US FDA approved pegylated interferon α-2b (Sylatron; Merck) for the treatment of melanoma patients with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy based on the EORTC 18991 trial.22
Medical management of myelodysplastic syndrome (MDS) remains a challenge, but in a clinical trial conducted by the EORTC together with the German MDS Study Group, it was shown that treatment with decitabine (Dacogen; Eisai), a drug that inhibits DNA methylation, significantly prolonged progression-free survival (PFS) in older, higher risk MDS patients.23
A significant improvement in patient quality of life This trial demonstrated the superior clinical efficacy
of Escherichia coli asparaginase over Erwinia chrysanthemi asparaginase in the treatment of childhood lymphoid malignancies during induction and reinduction, and this therapy is now a universal component of acute lymphoplastic leukaemia (ALL) treatment and is used in many paediatric regimens for ALL.
New Drug Development
The EORTC has also contributed to the development of improved drugs for treating cancer. Studies with imatinib (Glivec; Novartis) led to a dramatic improvement in overall survival in patients with metastatic gastrointestinal stromal tumours.18
Based on the results of an EORTC clinical trial, temozolomide (Temodar; Merck) was approved by the FDA for the treatment of adult patients with newly diagnosed glioblastoma multiforme.19
Carboplatin plus paclitaxel is the standard treatment for patients with non-small cell lung cancer, a treatment that was licensed following the landmark EORTC 08975 trial.20
One EORTC study set a
new standard of treatment for patients with acute myelogenous leukaemia and found that the long-term efficacy of chemotherapy
EUROPEAN ONCOLOGY & HAEMATOLOGY
(QoL) was also observed. Supportive Therapy
The work of the EORTC also encompasses treatments given to improve the management of complications associated with cancer treatment, such as infections and, in particular, Gram-negative sepsis and fungal infections.
A landmark study showed that infections due to Gram-negative bacilli could be managed best with a beta-lactam antibiotic and an aminoglycoside.24
They further showed that continuing the
aminoglycoside was not always necessary, thereby reducing the risk of toxicity.
In fungal infections, voriconazole (Vfend; Pfizer) was established as the drug of choice for treating invasive aspergillosis given its improved response, survival and severe side effect profile by comparison with amphotericin B. It is the benchmark against which other drugs are measured to establish an indication for treating invasive aspergillosis.25
Imaging
Incorporation of imaging technologies into clinical trials will enhance the delivery of appropriate treatments to patients. The EORTC has developed an Imaging Platform which will enable the development of
11 H8
Survival, %
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