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The role of the ‘innovative therapies for children with cancer’ (ITCC) European consortium

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Summary

Overall survival from childhood malignancies has dramatically improved, with survival rates now reaching over 70%. Nevertheless, some types of childhood cancer remain a difficult challenge, and for those who survive the burden of treatment can be considerable. The current paradigm for new cancer therapies is to increase our knowledge of the molecular basis of carcinogenesis, followed by the development of cancer-cell specific therapies. Historically, drug development was focused on adult cancers, and the potential efficacy in childhood malignancies was not considered. Recently, a European academic consortium was established, namely ‘innovative therapies for children with cancer’ (ITCC), to address this unmet need. This initiative is focused on the evaluation of novel agents in pediatric cancer pre-clinical models, and early clinical development of promising new drugs. The number of pediatric patients eligible to participate in such trials is limited, and accurate pre-clinical evaluation may provide evidence-based prioritization for clinical development. Until recently, clinical development of new drugs in childhood cancer was restricted by the limited accessibility of such agents. Recent changes in EU legislation oblige pharmaceutical companies to provide pediatric clinical data for all new drugs relevant to children, including anti-cancer drugs. Pediatric consortiums like ITCC have established networks of expertise with the specific aim of evaluating new drugs for the treatment of childhood cancers. Through proper evaluation in collaborative clinical trials we will learn how best to use these new therapeutic approaches and improve the survival rates and reduce toxicity for children with cancer.

Section snippets

Cancer in children

Childhood cancer can be divided into three broad sub-categories: leukemias, brain tumors (including benign tumors) and extra-cranial solid tumors, each comprising approximately one-third of the total number of cases of childhood cancer. The histology is significantly different from that observed in adults. In leukemias, acute lymphoblastic leukemia (ALL) is approximately 5–6 times more common than acute myeloid leukemia (AML), and chronic leukemias are rare. In solid tumors, carcinomas are rare

Improvement of outcome

Currently, approximately 70% of children with cancer can be cured. This has been achieved by stepwise improvements through sequential treatment optimization studies. These studies have fine-tuned the scheduling of currently available chemotherapy and other treatment modalities such as surgery and radiotherapy. However, the improvements in cure rates seem to have slowed down during the past decade, probably because we have reached the level where it is difficult to further improve outcome with

Changes in legislation in Europe

Until a few years ago, there was limited interest from pharmaceutical industries in Europe for drug development studies in children. For instance, Hirschfeld et al. investigated more than 100 drugs that had been approved by the FDA for the treatment of malignancies.28 Only 15 had pediatric use information in their labeling, which was less than 50% of the drugs commonly used in the treatment of pediatric malignancies. On January 27th 2007, a new legislation governing the development and

Ethical aspects

The need to develop new medicines for children is unquestionable. The risk/benefit ratio always needs to be evaluated at the individual patient level, and fair understandable information must be provided to the parents and/or the child, in line with local rules and regulations. Younger children may not be able to provide informed consent, and hence additional protection for this vulnerable group of potential participants is needed. An important aspect is the potential therapeutic benefit for

Increasing numbers of sub-groups

Due to the increased understanding of the pathophysiology of many types of childhood cancer, there are many new sub-groups identified with targets that are only present in a small sub-group of patients of a specific disease. This further subdivides these rare diseases in even rarer sub-groups. An example is KIT-mutated AML, which may be targeted with tyrosine kinase inhibitors, but which occurs only in approximately 10% of pediatric AML cases.41 In order to target this mutation, a European

Conclusions

Five years after its initiation, ITCC is a viable and well-established organization to address the challenges of new drug development for children with cancer. Current efforts are directed towards being a legal organization with a consortium agreement between the centers, to further improve the collaboration and the capacity to collaborate with pharmaceutical companies. The objectives discussed in this chapter have not changed, and the goal for the next 5 years is to further expand the number of

Conflict of interest statement

ITCC is an academic consortium. It is not funded by or dependent on funding of the pharmaceutical industry. None of the authors have conflicts of interest including specific financial interests, relationships, and/or affiliations relevant to the subject matter included in this manuscript.

Acknowledgement

The authors like to thank all centers mentioned in Table 1 for actively contributing in the ITCC consortium, and all others who have contributed either by referring patients or otherwise for their collaboration with ITCC.

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