Taxanes in paediatric oncology: and now?
Nicolas André1, Christophe Meille
1Department of Paediatric Oncology, EA3286, UFR of Medicine and La Timone Children Hospital, Bd. Jean Moulin, 13885 Marseille, Cedex 5, France. nicolasandre@ap-hm.fr
Abstract:
Taxanes are a group of anticancer agents that target microtubules, promote their assembly, and stabilize them. The resulting effects are mitotic blockage and induction of apoptosis, whose mechanism of initiation remains to be fully determined. Among adults, taxanes are one of the most powerful and most commonly used anticancer drugs. They show a wide range of activity in malignancies such as breast, ovarian, and lung cancers. In paediatric oncology, pre-clinical and clinical data are quite limited. Six phase I studies, two phase II, and rare case reports have been published. This review will focus on the paediatric pre-clinical and clinical findings with taxanes. Based on data from the literature, we will try to explain the results and foresee the possible use of taxanes in paediatric oncology. Indeed, three main advances have been made regarding taxanes: (1) Increased efficacy when used in multidrug-based chemotherapy regimen. (2) New administration schedules based on anti-angiogenic properties when given at daily very low doses. (3) Development of new taxanes with decreased recognition by Pgp, the product of the MDR1 gene. Thus, although the initial experience with taxanes in paediatric oncology has been disappointing, it may be too early to leave out taxanes and we should further investigate their use among children with cancer.
Insights
Taxanes are potent anticancer drugs for adults, but their use in children is limited. Further research is needed to explore taxane efficacy and new administration schedules for paediatric cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Taxanes are microtubule-targeting anticancer agents widely used in adult malignancies.
- Their mechanism involves mitotic arrest and apoptosis induction.
- Limited pre-clinical and clinical data exist for taxane use in paediatric oncology.
Purpose of the Study:
- To review paediatric pre-clinical and clinical findings with taxanes.
- To explain current results and forecast future applications of taxanes in paediatric oncology.
- To highlight recent advances in taxane therapy.
Main Methods:
- Literature review of published paediatric pre-clinical and clinical studies.
- Analysis of case reports and phase I/II studies.
- Synthesis of data to evaluate taxane efficacy and potential.
Main Results:
- Taxanes demonstrate efficacy in adult cancers like breast, ovarian, and lung.
- Advances include combination chemotherapy, low-dose daily schedules for anti-angiogenesis, and novel taxane development.
- Initial paediatric experiences have been disappointing.
Conclusions:
- Despite disappointing initial results, taxanes hold potential for paediatric oncology.
- Further investigation into taxane efficacy and novel administration is warranted for childhood cancers.
- Combination regimens and new taxane analogs may improve outcomes.
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